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2019 ASCCP Oral Presentation Abstracts

Journal of Lower Genital Tract Disease: April 2019 - Volume 23 - Issue 2S - p S11–S28
doi: 10.1097/LGT.0000000000000470
2019 ASCCP e-Poster Presentations
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Anal/Perianal

Anal Cancer Screening Among Hispanic Women With Lower Genital Tract Neoplasia in Puerto Rico

Josefina Romaguera2, Ana P. Ortiz1, Sandra Garcia-Camacho1, and Vivian Colon1. 1University of Puerto Rico Comprehensive Cancer Center, 2Medical Sciences Campus

Objective: An excess risk of anal cancers and anal intraepithelial neoplasia among women with lower genital tract neoplasia (LGTN) has been established. An expert review, including the American Society for Colposcopy and Cervical Pathology and the International Anal Neoplasia Society, recommends anal cytology screening for these women, in settings where HRA and treatment is available. Given the existence of an Anal Neoplasia Clinic in Puerto Rico (PR), this study describes awareness, experience, and attitudes towards anal cancer screening among women with LGTN.

Methods: Ongoing clinic-based cross-sectional study (May-October 2018) among women receiving services at the colposcopy, gynecology oncology and lower genital tract clinics of the University of PR. Women complete an interviewer administered questionnaire and the medical record is reviewed for LGTN diagnosis. From consecutive women invited (response rate=67%), n=74 with LGTN consented to participate; 93% (study population, n=69 women) completed anal cancer questions.

Results: 85.5% of women have cervical, 10.4% vulvar, and 11.6% vaginal LGTN. Mean age is 54.6 years (SD=1.86) and 36.2% have had ≥1 anal cancer symptoms in the past 12 months (anal bleeding, pain or itching). Only 14.5% and 13.0% of women have ever heard of or had an anal pap, respectively. 79.4% recognize not knowing anything about it, although 98.5% say that they would do the test if their doctor recommended it.

Conclusions: Awareness of and experience with anal cancer screening is low in this sample of women with LGTN in PR, justifying the need for education in this topic for patients and physicians.

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HPV Prevalence of Rectal and Scrotal Carcinomas in the United States

Jacqueline Mix1, Mona Saraiya1, Aprl Greek2, Elizabeth Unger1, Trevor Thompson1, Troy Querec1, Thomas Tucker3, Charles Lynch4, and Edward Peters5. 1CDC, 2Battelle Memorial Institute, 3University of Kentucky, 4University of Iowa, 5Louisiana State University

Objective: Rectal squamous cell cancers (SCC) are morphologically similar to anal cancers and are thought to be caused by HPV. HPV has also been associated with scrotal cancer. We examined prevalence of HPV types in rectal and scrotal cancers in comparison with anal and penile cancers in the US.

Methods: Archived tissue from invasive scrotal carcinomas, rectal SCC, and anal carcinomas diagnosed during 2014- 2015 were identified from 3 population-based cancer registries and genotyped using L1 consensus PCR with type-specific hybridization. Overall and type-specific weighted HPV prevalence was determined. Preventable fractions of cancers were estimated using hierarchical proportion to HPV 16 and 18 oncogenic genotypes included in all vaccine formulations (16/18) and protection from 5 additional types in the 9-valent vaccine (31/33/45/52/58). Weighted prevalence of p16 was determined for rectal and scrotal cancers. We compared scrotal prevalence to penile prevalence from an earlier similar US study.

Results: 73 anal, 39 rectal and 6 scrotal cancers were successfully genotyped. Prevalence of any HPV, HPV 16/18 and HPV 31/33/45/52/58 varied by anatomic site: Anal: 90.6% [16/18: 85.1%, 31/33/45/52/58: 3.1%]; Rectal: 82.4% [16/18: 71.4%, 31/33/45/52/58: 11%]; Scrotal: 66.6% [16/18: 50%, 31/33/45/52/58: 0%]. Prevalence of p16 in rectal and scrotal cancer was 78% and 50%, respectively. HPV prevalence of penile cancers (n=79) was 63% [16/18: 47.9%, 31/33/45/52/58: 9.0%].

Conclusions: HPV prevalence for rectal SCC are similar to anal carcinoma and scrotal carcinoma prevalence is similar to penile carcinomas. These estimates are a useful baseline measure to monitor impact of vaccines on these cancers.

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Prevalence and Risk Factors for Intraepithelial Injury and Anal HPV in Women With HGISL and Cervical Carcinoma In Situ

Marcos Castillo2, Sandra Gomez1, Evelyn Puentes2, Jairo Amaya2, Daniel Sanabria S3, and Olga Restrepo2. 1Hospital de la Samaritana, 2Universidad de la Sabana, 3Fundacion Santa Fe de bogota

Objective: To determine abnormalities in anal cytology, the frequency of anal HPV infection, the prevalence of anal intraepithelial neoplasia, and to explore risk factors for anal HPV infection and AIN in patients with high grade cervical lesion.

Methods: Design: Cross-sectional study.

Setting: Patients with high grade intraepithelial squamous lesion attending the cervical pathology clinic in two institutions in Bogota, Colombia.

Patients:124 patients between 21 and 65 years of age who attended the cervical pathology clinic.

Sociodemographic, sexual behaviour and pathological history data were collected. Anal samples were taken for cytology and HPV DNA detection, and high-resolution anoscopy. Data were analysed using the Stata 15 software package, and the frequency of HPV infection, anal intraepithelial lesion and abnormal cytological findings was estimated. A logistic regression analysis with a 95% confidence interval and statistical significance of p<0.05.

Results: 124 women with a histopathological diagnosis of CIN2/3 and carcinoma in situ and a mean age of 38 years (IQR 32-44) were included. Four women were found to have positive cytology for ASCUS, and the remaining were negative for intraepithelial lesion; in 14 women (11.7%), anoscopy was abnormal and targeted biopsy was performed; 8 women (6.7%) had anal intraepithelial lesion (7 with low grade anal intraepithelial neoplasia and 1 with high grade AIL). HPV infection was found in 47 women (37.8%), and the genotypes identified were HPV 16, 18 and other high risk genotypes. Risk factors for anal HPV infection included more than three sexual partners (OR 1.57; 95% CI 0.70-3.60) and age of first child 21 years [OR 1.07; 95% CI 1.01 – 1.15]. Having had more than three deliveries was found to be a protective factor (OR 0.42; 95% CI 0.19 – 0.96). None of the risk factors for AIN that were evaluated were statistically significant.

Conclusions: The presence of anal HPV in the group of cervical intraepithelial lesion in the study population is similar to that reported in the literature with evidence of AIL, constituting a precursor lesion for anal cancer. The impact of adequate and timely treatment has already been demonstrated in cost-effectiveness studies.

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Screening for Anal Cancer in Women With a History of Vulvar Intraepithelial Neoplasia

Lily Proctor1, Annick Pina2, Susan Keast1, Arianne Albert1, Troy Grennan1, Leslie Sadownik1, and Marette Lee1. 1University of British Columbia, 2Centre Hospitalier de l' Université de Montréal

Objective: To determine the prevalence of (1) a positive anal cancer screen and (2) anal intraepithelial neoplasia (AIN) in women undergoing surveillance for previously diagnosed and treated vulvar intraepithelial neoplasia (VIN). Secondary objective was to determine the patients’ acceptability of the anal screening process.

Methods: This is a Canadian, single institution, cross-sectional pilot study. Women, age 30-80, with biopsy proven VIN2 or VIN3 were invited to undergo screening for anal cancer. Screening consisted of: anal HPV test, anal cytology and digital ano-rectal exam. Positive screen characterized by abnormalities in any one of the above. All women with an abnormal screen were referred for high resolution anoscopy (HRA). All women completed a post-screen questionnaire to determine the acceptance of the screening exam.

Results: 57 patients were recruited. The median age was 61.5 (IQR 51.0-68.0). Median time since first VIN diagnosis was 13.0 years (IQR 10.0-24.0). 50.8% of patients had a history of another lower genital tract lesion (cervical, perianal, vaginal). The prevalence of a positive screen was 56.1% (95%CI = 43.3, 68.2%). Of the 32 screen positive patients, 12 (37.5%) had both abnormal cytology and high risk (HR)-HPV, 3 (9.4%) had positive HR-HPV alone and 17 (53.1%) had abnormal cytology alone. The prevalence of AIN2+ among those who had screening was 18.9% (95%CI = 10.6, 31.4%). Positive predictive value of positive screen for AIN2+ was 31.2%. The exam was well tolerated with 100% of patients indicating that they would have the screening again.

Conclusions: Women with VIN have an increased risk of developing high grade AIN. Screening for anal cancer in this population should be considered.

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Transcriptionally Active HPV in Squamous Intraepithelial Lesions Arising From Anal Transition Zone

Yiying Wang1, Wenxin Zheng2, and Yuxin Liu3. 1Henan Provincial People's Hospital, 2UT Southwestern Medical Center, 3The Mount Sinai Hospital

Objective: HPV-induced squamous cell carcinoma arising from the anal transitional zone has poor prognosis with significantly increased morbidity and mortality. Two distinct cell populations have been described for this region: CK7-positive superficial columnar cells and p63-positive basal cells. In this study, we aimed to identify these two cell populations in anal cancer precursors as well as their co-localization with transcriptionally active HPV in the anal transitional zone.

Methods: 16 anal high-grade squamous intraepithelial lesions (HSIL) were included in the study. Two biopsy samples from benign anal transitional zone mucosa were used as control. Immunohistochemistry was performed using antibodies against CK7 and P63. HPV E6/E7 expression was performed on Formalin-Fixed Paraffin-Embedded tissue using RNAscope in situ hybridization (ISH).

Results: All HSIL lesions revealed multilayers of CK7-positive cells in the superficial portion of the dysplastic epithelium as well as p63-positive basal cells above basement membrane. P63-positive cells were arranged in one to four continuous cell layers. Positive HPV 16 E6/E7 signals were detected in all lesions. However, the distribution and cellular location of E6/E7 signals varied significantly among lesions: focal positivity within CK7-positive cells in 5 cases, focal positivity within P63-positive cells in 4 cases, and diffuse positivity involving both CK7 and P63-positive cells in 7 cases. No HPV E6/E7 signals were detected in negative controls.

Conclusions: We confirmed the presence of two distinct cell populations in anal cancer precursors arising from the transitional zone. Both cell populations harbor transcriptionally active HPV 16 E6/E7 RNA. Further study of the relationships between transitional zone cells, HPV 16 E6/E7 localization and lesional progression would be of great value.

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Cervical Cancer

A Case Investigation of Cervical Cancer and Screening Prior to Diagnosis in Women From Three U.S. States, 2013-2016

Virginia Senkomago1, Aprl Greek2, Warner Huh3, Cheryll Thomas1, and Vicki Benard1. 1U.S. Centers for Disease Control and Prevention (CDC), 2Battelle, 3University of Alabama at Birmingham

Objective: To examine barriers to routine screening and follow-up of abnormal results among women diagnosed with cervical cancer.

Methods: Women aged 21-65 years with cervical cancer diagnoses reported in state cancer registries in Louisiana, Michigan and New Jersey (2013-2016), were invited to complete a mailed survey. We analyzed data from 489 women, assessing: (a) routine Pap or HPV screening in 5 years prior to diagnosis; and, reasons women reported for screening or not; (b) abnormal results prior to diagnosis; following up; and, reasons for not following up as directed.

Results: About half of the women (47%) reported not getting any screening tests in the five years prior to diagnosis. Key reasons for not being screened were: not thinking that they would develop cervical cancer (77%); no family history of cervical cancer (59%); not having a regular health care provider (51%); no health insurance (45%); and, being too busy (40%). In total, 84% of women reported an abnormal Pap test result prior to diagnosis; of these, 12% did not follow-up and 15% waited longer than recommended. Key reasons for not following up included not realizing an abnormal result could indicate cervical cancer (54%) and being scared to hear meaning of an abnormal result (43%).

Conclusions: Roughly half of these women diagnosed with cervical cancer did not receive appropriate screening. Reasons for not being screened suggest gaps in access to care and knowledge of cervical cancer, screening tests and results. Addressing these barriers could increase screening coverage and reduce cervical cancer incidence. These findings do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention.

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A Cross-Sectional Pilot Survey of Health Status and Cervical Cancer Screening Beliefs After 65 Years of Age

Deanna Teoh1, Rida Shaikh1, Tiaj Xiong1, Jinai Bharucha1, Shalini Kulasingam1, and Eileen Harwood1. 1University of Minnesota

Objective: To assess the association between health status and agreement with the guideline recommendation to stop cervical cancer screening after age 65 years.

Methods: A cross-sectional survey of United States women >65 years of age was conducted via Facebook over two weeks. Demographic data, cervical cancer screening history and beliefs, and health history were self-reported. Life expectancy was calculated from the self-reported data using the validated Lee Schonberg Index. Participants who agreed/disagreed with the guidelines were compared using Chi-squared tests.

Results: 49 eligible women responded; most were 66-69 years of age (69%) and reported regular cervical cancer screening prior to age 65 years (87%). Half (49%) had discussed screening cessation after age 65 years with a healthcare provider. Almost half (43%) disagreed with screening cessation, and 80% thought there should be no stopping age. A majority (87%) considered themselves healthy, and anticipated life expectancy generally agreed with calculated life expectancy. However, subjectively unhealthy participants were more likely to disagree with the recommendation to stop screening than healthy participants (25% vs. 0%; p=0.02). However, there was no difference in screening beliefs by calculated mean life expectancy (agree 20.3±6.0 years vs. disagree 18.6±6.4 years; p=0.78).

Conclusions: Surprisingly, poorer subjective health status was associated with a desire to continue cervical cancer screening past age 65 years. A larger study is needed to confirm the results of this pilot survey, but these results suggest both health status and age need to be included in patient-centered discussions regarding cessation of cervical cancer screening.

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A Multi-Disciplinary Quality Improvement Approach Decreases Rates of Insufficient Pap Smears

Markeiya Polite1, Eliza Rodrigue1, Nia Thompson1, and Stacey Holman1. 1Lousiana State University Health Sciences Center

Objective: Nationally, 2% of pap smears are resulted insufficient, leading to missed diagnoses, increased healthcare burden, and patient inconvenience. Blood, inflammation, scant cellularity, and provider error are common reasons for insufficiency. In the Louisiana State University (LSU) OBGYN resident clinic in 2016, a 4-fold increased rate of unsatisfactory results prompted investigation. We aimed to implement a clinical quality improvement (QI) initiative to decrease rates of insufficient results due to collection technique and preparation error.

Methods: In January 2018, a multidisciplinary QI initiative was conducted. This included resident and nursing education with Hologic™ and implementation of Carbomer-free lubricant clinic wide. Pap smears collected in clinic from July 2016 to June 2018 were reviewed. Data from July 2016 to June 2017 was then compared to data from February 2018 to June 2018 (post-initiative).

Results: Following the QI initiative, 490 pap smears were reviewed with a 6.9% (n=34) unsatisfactory rate. This decreased from 2016-2017 7.9% unsatisfactory rate. Sixty percent of insufficient results were due to a combination of factors (i.e. Scant cellularity, inflammation, blood); isolated excessive lubricant (3%) was also a cause. Pre-initiative, 10% of insufficient results were secondary to excessive lubricant.

Conclusions: After implementation of this QI initiative, there has been a decrease in the percentage of unsatisfactory pap smears. Additionally, the number of insufficient specimens related to thick lubricant preparations decreased. This study has highlighted the importance of ongoing education for nurses and residents regarding proper collection techniques for optimal accuracy of pap smear results.

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Clinical Evaluation of Cold Knife Conization for Diagnosis and Treatmentto Cervical Cancer Patients

Chao Zhao1, Jianliu Wang1, Yan Liu2, Dan Wang3, Xuechun Xu4, and Lihui Wei1. 1Peking University People's Hospital, 2Changping District Traditional Chinese Medicine Hospital, 3Liupanshui Maternal and Child Health Hospital, 4Friendship Hospital

Objective: To evaluate the clinical value of conization in the diagnosis and treatment of cervical cancer patients?

Methods: 137 patients diagnosed with cervical cancer after cold knife conization in Peking University People’s hospital between 2008.1 and 2016.12 were reviewed? The pathological profiles of conization specimens and treatment options were analyzed?

Results: There were 127 squamous cell carcinomas, 8 adenocarcinomas, 1 neuroendocrine carcinoma and 1 adenoid basal carcinoma. In 127 squamous cell carcinomas, there were stage Ia1(n=82), stage Ia2 (n=6)and stage Ib1(n=39)?In 8 adenocarcinomas, there were stage Ia1(n=3), stage Ia2 (n=2)and stage Ib1(n=3)?Among 41 patients with stage Ia1 squamous cell carcinomas undergoing further surgery,14 (34.1?)had residual diseases, including CIN 2(n=9), CIN3(n=4)and squamous cell carcinoma(n=1)?No recurrence was found in 41 cases without further surgical intervention. All cases of stages Ia2 and Ib1 underwent repeat surgery?

Conclusions: Cold knife conization plays a very important role in the diagnosis and treatment of cervical cancer patients?

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Comparison of Triage Management Between p16INK4a/Ki67 Dual Staining and HR-HPV Test in Patients With ASC-US and LSIL

Li Geng1, Xuefei Ge1, Ke You1, Yanli Guo1, and Yi Li1. 1Peking University Third Hospital

Objective: To compare the triage management between p16INK4a/Ki67 dual staining and HR-HPV test detection in patients with cervical cytology ASC-US and LSIL.

Methods: 143 patients with cervical cytology results as ASC-US and LSIL were enrolled in the gynecological clinic of the Third Hospital of Peking University from June 2016 to July 2018. The average age was 38.83 years. All the participants underwent dual staining test of p16INK4a/Ki67, HR-HPV test, colposcopy and biopsy. CINtec PLUS kit (Roche, USA) was used for p16INK4a/Ki67 dual staining and Cobas 4800 detection system (Roche, USA) was used for HR-HPV test.

Results: A total of 143 participants were enrolled with 86 ASC-US cases (86/143, 60.1%) and 57 LSIL cases (57/143, 39.9%). Cervical biopsy results showed that 35 cases (35/143, 24.5%) were ≤CIN1, 72 cases (72/143, 50.3%) were CIN2, 29 cases (29/143,20.3%) were CIN3 and 7 cases (7/143, 4.9%) were cervical cancer. In patients with cervical cytology results as ASC-US and LSIL, the sensitivity of p16INK4a/Ki67 dual staining and HR-HPV test for detection CIN 2 or above were 85.2% and 75.4% (p=0.078), with the specificity of 54.3% and 22.2% (p<0.001), and the AUC of ROC curve was 0.697 (95%CI 0.615-0.771), 0.504 (95% CI 0.419-0.588) (P < 0.001), and referral rate of colposcopy was 75.5% and 93.7% (p=0.001).

Conclusions: In patients with cervical cytology ASC-US and LSIL, p16INK4a/Ki67 dual staining shows a higher specificity in detecting lesions of CIN2 or above and lower referral rate of colposcopy than that of HR-HPV test, and the sensitivity was also higher in p16INK4a/Ki67 dual staining. In patients with cytological ASC-US and LSIL, p16INK4a/Ki67 dual staining triage was more effective than HR-HPV test in detecting CIN2 or above lesions.

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Dominican Provider Attitudes Towards Practice Change for Cervical Cancer Screening in Santo Domingo and Monteplata

Erica Liebermann1. 1New York University

Objective: The Dominican Republic has high cervical cancer rates despite decades of Pap smear screening. Evolving evidence supports the use of human papillomavirus (HPV) testing for cervical cancer screening, particularly in places with nonexistent or ineffective screening programs. Little is known about provider perceptions of existing Pap smear screening programs in the Dominican Republic, nor potential barriers and facilitators to changes in screening practice. The purpose of this study was to examine Dominican providers’ attitudes towards HPV testing for cervical cancer screening.

Methods: This was the qualitative portion of a mixed methods study examining barriers to adoption of evidence-based practice for cervical cancer prevention. Sixteen individual interviews were conducted with doctors from Santo Domingo and Monteplata provinces. Guided by the Consolidated Framework for Implementation Research, the interview guide was structured by constructs known to be relevant to successful implementation of public health interventions. Qualitative data analysis utilized both inductive and deductive approaches.

Results: General receptivity to HPV testing was high, as it is already used to complement Pap testing in the private sector. Providers were not aware of HPV testing as primary screening. Barriers to adoption were cost and recommended screening age. Providers feared Dominican women were at earlier risk for cervical cancer.

Conclusions: Limited knowledge of HPV’s superior test performance impacts provider estimation of the benefits of a change in screening modality. Sharing of Latin American experiences with implementation of HPV screening and generation of in-country data would strengthen the case for HPV testing as an effective screening method in the Dominican context.

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HPV Typing as Part of Cervical Screening and Management of HPV-Positive Women

Maria Demarco1, Noorie Hyun2, Li Cheung1, Nicole Campos3, Anne Hammer4, Philip Castle5, Julia Gage1, Brian Befano6, Barbara Fetterman7, Nancy Poitras7, Tom Lorey7, Tina R. Raine-Bennett7, Nicolas Wentzensen1, and Mark Schiffman1. 1National Cancer Institute, 2Medical College of Wisconsin, 3Harvard T.H. Chan School of Public Health, 4Aarhus University, 5Albert Einstein College of Medicine, 6Information Management Services, Inc., 7Kaiser Permanente Northern California

Objective: The role of HPV typing in cervical screening and management of HPV-positive women is still unclear. We studied the clinical meaning of HPV type for predicting progression to precancer versus viral persistence versus clearance.

Methods: We collected residual HPV test specimens from 35,433 women testing positive from among 823,341 women aged 30-65, cotested with HC2 and cytology at NCI-Kaiser Permanente Northern California. We typed a stratified random sample of 10,801 specimens, focusing on women diagnosed subsequently with CIN2+ and a sample of controls. Subcohorts of women with each of the high-risk HPV types were followed to determine competing risks of progression, persistence and clearance.

Results: Risk of progression substantially differed by type; as expected, HPV16 conveyed substantially higher risk. The important role of HPV18/45 in causing invasive cancers was not evident in this intermediate-length follow-up study. The remaining HPV types could be further stratified into intermediate (HPV31, 33, 52, 58, and sometimes HPV35) and lower risk groups. Knowing HPV type was more informative than cytology (except HSIL+) in triage of HPV positive women. By year 3, most HPV-positive women had cleared or progressed. Absent progression, viral clearance did not vary substantially by type. Clearance was higher for incident infections. By the end of follow-up, virtually no infections were persistent without progression.

Conclusions: In a large clinical follow-up of HPV-infected women, we demonstrated that HPV genotyping stratified subsequent risk of precancer within 3 years of follow-up. The usefulness of extended HPV typing should be determined by cost-effectiveness analyses.

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Morbid Obesity, BMI ≥ 40: Effects on Cervical Cancer Screening and Presentation

Kelsey Sheets1, Hayley Hansen1, Colette Gnade1, Emily Hill1, Abbey Hardy-Fairbanks1, and Colleen Stockdale1. 1University of Iowa

Objective: 39. 8% of adult Americans are obese. Obese patients have a greater risk of developing certain cancers and face worse outcomes. Morbid obesity is suggested to be an independent risk factor for death from cervical cancer. This study aims to investigate the impact of obesity on cervical cancer presentation, stage, and screening rates. Hypotheses: Obese and morbidly obese women are more likely to present with symptomatic cervical cancer, to be diagnosed at a later stage, and to have had inadequate cancer screening.

Methods: IRB approved retrospective cohort study of cervical cancer patients from the University of Iowa Hospitals and Clinics between 1986-2018. Patient populations were compared by cervical screening history, presence of symptoms, and stage of disease.

Results: Our cohort had 668 patients: 262 obese, 387 non-obese, and no weight data for 19 patients. 66 of 262 were morbidly obese. 34. 3% of obese women had routine PAP screenings vs. 42. 6% of non-obese women (p = 0. 03). 28. 8% of morbidly obese women had routine screening (p = 0. 02). 74. 2% of morbidly obese patients had symptomatic cervical cancer vs. 59. 8% of obese patients (p = 0. 03). 12. 5% of obese women presented with advanced diagnosis vs. 14. 6% of non-obese patients (p = 0. 44).

Conclusions: Obese women were less likely to have routine cervical cancer screening. This is especially true of morbidly obese women, who were even less likely to have routine screening and were more likely to present with symptoms. Disparities in screening may be secondary to healthcare access barriers that disproportionately affect obese women.

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Pap Cytology and HPV Testing Associated With 187 Histological Diagnoses of Cervical Glandular Neoplasias

Chengquan Zhao1, and Stell Patadji1. 1UPMC

Objective: To evaluate screening test histories of women with histological cervical adenocarcinoma in situ and invasive adenocarcinoma.

Methods: A 187 patients with histological diagnoses of cervical invasive or in situ adenocarcinomas were identified from our pathology database from 7/2009 to 6/2018. Pap cytological and HPV testing results were recorded for 128 patients with cervical adenocarcinoma in situ and 59 patients with invasive cervical adenocarcinoma.

Results: The patients’ average age was 43 years (23-86 years). Of the 187 cervical glandular neoplasias, 68.0% had coexisting histological squamous CIN (CIN1-3) diagnoses. Among the 163 cases of cervical glandular neoplasia with Pap test result within 1 year before histological diagnoses, 153 (93.9%) had an abnormal Pap test and 10 (6.1%) had a normal Pap test. Abnormal glandular Pap cytology was the most common test, 49.1% (100/163). The negative Pap test rate was increased to 44.9% in the period between 1-3 years before the histological diagnoses. The negative Pap test rate appeared higher in AIS patients than invasive adenocarcinoma patients. A total of 123 patients had HPV testing results within 1 year before histological diagnoses. The HPV positive rate was 92.7%. Of the 60 patients with HPV testing results 1-3 years before histological diagnoses, the HPV positive rate was 78.3%.

TABLE 1

TABLE 1

Conclusions: The negative Pap and HPV test rates within 1 year before glandular histological diagnosis were similar (6.1% vs 7.3%). About 21.7% of the patients had a negative HPV test result 1 -3 years before histological diagnoses of AIS or invasive adenocarcinoma. Our study indicated that Pap cytology and HPV cotesting facilitates early detection of cervical glandular neoplasias.

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Performance of Cytology and NGS-HPV Testing in a Population-Based Cervical Cancer Screening Program

Ping Zhou1, Huanxia Zhong1, Yutao Du2, Zhang Lin2, Haina Guo1, Guozheng Hu2, Yongmei Zhang1, Lihui Wei3, Jerome Belinson4, and Xinfeng Qu4. 1Dongguan Women and Infants Hospital, 2Shenzhen BGI Corporation Ltd, 3Peking University People's Hospital, 4Preventive Oncology International Inc

Objective: Evaluate the performance and costs associated with NGS-based HPV genotyping assay and cytology in a population-based cervical cancer screening program.

Methods: Screening was conducted by direct sample co-testing in Dongguan, China 2012-2018. $15,080,000 funding, 114 doctors from 38 hospitals were involved. Women aged 35-59 were eligible for participation. Women HPV or cytology positive (≥ASCUS) were triaged. Biopsies were requested on HPV16/18 positives, non-16/18 with positive cytology, and/or all positive cytology. Patients were requested to repeat screening in 3 years. Cost analysis was done for the individual tests.

Results: 252,650 women were screened. 109,410 women were re-screened in 3-5 years. 362,060 individual tests were done with a per-case cost of $41.64. HPV testing detected 96.83% (917/947) of the CIN2+ patients ($3,999.16 /CIN2+); while cytology detected 78.14% (740/947) equaling to $13,695.89/CIN2+. Cytology missed 22% (207) of the CIN2+ but detected 30 CIN2+ (3.17%) that were HPV negative. Since all were co-tested, cytology was used only to triage non-16/18 HPV positives, making its cost to be $27,957.72/CIN2+. The trackable positive management rate was 18.86% of the triaged positives. If 80% of the defined positives could be managed appropriately the cost of HPV testing and cytology would be $942.80 and $3,228.80 per CIN2+ respectively; and triage cytology would be $6,591.03/CIN2+.

Conclusions: 1) HPV-genotype-based triage is effective in large population-based screening programs. 2) Cytology (co-testing) adds great cost to population screening with little added benefit. 3) Effective callback for positive management is the key determinant of a successful screening program.

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Pregnancy Outcomes Following Fertility Preservation in Women With Cervical Adenocarcinoma In Situ

Ran Zhang1, Nujsaubnusi Vue1, Lisa Obasi1, Rachel Isaksson Vogel1, Amar Subramanian2, Mahmoud Khalifa1, Buvana Reddy2, and Britt Erickson1. 1University of Minnesota, 2Health Partners

Objective: To evaluate pregnancy outcomes among women with cervical adenocarcinoma in situ (AIS) who opted for fertility-sparing treatment, such as cold knife cone (CKC) or loop electrosurgical excision procedure (LEEP).

Methods: This is a retrospective case series of patients with cervical AIS. Patients were identified through pathology department databases from two hospitals in a large urban area. Data was abstracted including age, parity, procedure type, and pregnancy outcomes. Descriptive statistics were used to report outcomes.

Results: One hundred sixty-eight patients were identified with AIS from 2007-2017 and 27 patients (16.1%) underwent fertility preserving treatment. The average follow-up was 6.5 years (range 7 months – 11 years). Of the 27 patients, the average age was 29 years (range 18 – 35 years) and average parity was 1 (range 0 - 5). Eleven patients underwent CKC (40.7%) and 16 underwent LEEP (59.3%). Only 1 patient required a repeat CKC to treat recurrence. There were a total of 43 pregnancies among the 27 patients. Two women had 0 pregnancies; 13 women had 1 pregnancy; 8 women had 2 pregnancies; 4 women had 3 or more pregnancies. Six patients eventually received a hysterectomy. One patient (3.7%) required a cerclage. There were 22 (51.1%) full-term deliveries, 6 preterm deliveries (14.0%), 9 first-trimester spontaneous abortions (20.9%), 3 elective abortions (7.0%), and 3 (7.0%) unknown outcomes. Of the 6 preterm deliveries, 5 were induction of labor or C-section due to maternal/fetal indications; 1 was a result of preterm labor at 32 weeks and 5 days. There were a total of 9 (20.0%) C-sections.

Conclusions: Conservative management of women with AIS who desire fertility can result in comparable pregnancy outcomes of the general population. Specifically we found low preterm labor (2.3%), low rates of pre-term births (14.0%) and low rates of cerclage (3.7%). Fertility preservation should remain an option for women with AIS.

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Prevalence of Cervical Cancer and Screening Practices Among Women Living in an Underserved Urban Community in Accra

Priscilla Vandyck-Sey1, Roberta Lamptey1, Henry Lawson2, and Akye Essuman2. 1Korle Bu Teaching Hospital, 2College of Health Sciences, University of Ghana

Objective: To determine prevalence of cervical cancer (CC); to assess the risk factors to developing CC; and to evaluate screening practices of women 15 to 75 years at Korle Gonno, next to the largest teaching hospital in Ghana

Methods: This was a community-based cross-sectional study of women aged 15 to 75 years with subsequent screening for CC in a health facility. Participants were assessed on knowledge of CC and uptake of cervical cancer screening (CCS) using mixed methods. All respondents were interviewed in the community and then invited for a free risk factor assessment of Human Papilloma Virus (HPV) presence and Liquid-based cytology (LBC)

Results: A total of 174 women were interviewed aged 16-74 years (40.3±13.1) years out of whom 14.9% and 32.8% had heard of CCS and CC respectively. Their uptake of CCS was 2.3%. Traditional risk factors prevalent in the 72 women who obliged the health facility screening were Abnormal Cytology (5.6%), LSIL (4.2%), ASCUS (1.4%) and NILM formed 94.4%. Crude HPV prevalence was 12.5%. High risk HPV constituted 55.6% out of which HPV-16 formed 33.3%. Of the respondents, 50% had Age at First Sexual Intercourse (AFSI) ≤ 18 years; 68% had parity≥ 4; and 61.1% had >2 lifetime sexual partners. Non-traditional risk factors assessed were general obesity (53%) and truncal obesity (72.2%). Focused Group Discussion findings confirmed information obtained from structured questionnaires.

Conclusions: Awareness of CC is low and uptake of CCS is extremely low, for a community living in close proximity to the largest teaching hospital in Ghana. Vigorous education and community-based interventions need to be utilised to improve awareness of cervical cancer and uptake of cervical cancer screening in the community and Ghana as a whole.

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Relationship of Demographics and Method of Cervical Cancer Diagnosis

Kelsey Sheets1, Hayley Hansen1, Colette Gnade1, Emily Hill1, Abbey Hardy-Fairbanks1, and Colleen Stockdale1. 1University of Iowa

Objective: While cervical cancer screening has significantly reduced mortality and morbidity from cervical cancer, screening in the US is opportunistic. Non-specific symptoms of cervical cancer delay patient diagnosis. Aim: identify potential associations between presentation and demographics among women with a diagnosis of cervical cancer.

Methods: Retrospective study of women referred for cervical cancer between January 1, 1986 and September 6, 2017 including demographics, diagnostics, treatment and outcomes. Chi-square tests and t-tests were performed as appropriate with p<0.05 considered significant.

Results: Of 665 patient records reviewed, 431 were symptomatic at the time of cervical cancer diagnosis. The mean age at diagnosis for symptomatic women was 49.31(±14.09) years, versus 42.15(±13.01) years for asymptomatic women (p<0.001). 258 women had at least one pap in a 5-year period (women £65 years) or a negative pap within 5 years of screen-out at age 65. 143 were symptomatic and 115 were asymptomatic at cervical cancer diagnosis (p=0.02). Of 246 women not screened within 5 years, 191 were symptomatic and 55 were asymptomatic (p=0.77).

Conclusions: Women 341 years are more likely to present with symptoms at cervical cancer diagnosis in comparison to their younger counterparts. Women who received cervical cancer screening within 5 years were twice more likely to be asymptomatic at the time of diagnosis than those without. This is consistent with the average age of early cervical cancer diagnosis of 42 years in the U.S. and that women with cervical cancer diagnosis at an earlier age are more likely to be identified via routine screening.

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Result of the Excision of the Atypical Transformation Zone of 2918 Cases En El Hospital Oncologico SOLCA Quito Ecuador

Leopoldo Tinoco1, Angelo Nicolalde1, Ramiro Tinoco2, Cecilia Carrión1, Diana Tinoco2, and José Reyes3. 1Hospital Oncológico "SOLCA"Quito, 2Hospital IESS Quito SUR, 3Universidad Central del Ecuador

Objective: Evaluate the technique of EZTAT in patient with cervical pathology, and his versatility to identify and eliminate the atypical transformation zone.

Methods: Descriptive epidemiological studies of collected cases between 2008 to 2018 of patients with cervical-uterine pathology biopsy carriers of HSIL, suspected invasion or discordance, who went to the service of Pathology of the Lower Genital Tract of the Hospital SOLCA Quito- Ecuador

Results: We performed 2918 procedure in women between 17 to 98 years, it was found 7 cases of invasive adenocarcinoma, 10 minimal invasive adenocarcinoma, 23 In Situ adenocarcinoma, 27 invasive squamous carcinoma, 47 minimal invasive squamous carcinoma, 256 In Situ, 860 CIN III, 583 CIN II, 361 LSIL, 588 chronic cervicitis, 13 polyps, 8 leiomyoma, 1 radiotherapy’s change, 1 endometrial sarcoma and 1 cervical hemangioma. It was obtained, residual neoplasia with edges 133 (4.56%) vs neoplasia free 2785 (95.44%).

Conclusions: The versatility of “EZTAT” was obviously in your coverage, there isn’t age limit, and neither cervix conization can’t do. It helps to keep expectative pregnancy, and it can do it also in pregnant women and menopause late.

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Survival of Locally Advanced Adenocarcinoma Cervical Cancer With or Without NACT Treatment Before Surgery

Nayiyuan Wu1, Jing Wang1, Peilin Ouyang2, and Jingting Cai2. 1Hunan Cancer Hospital, 2Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University

Objective: We performed a retrospective study to compare the intermediate survival and long-term survival of patients with locally advanced adenocarcinoma cervical cancer (IB2-IIB) treated with neoadjuvant chemotherapy(NACT) followed by radical hysterectomy and pelvic lymph node dissection with the survival of those treated with neoadjuvant chemo-radiationtherapy(NACRT) followed by radical hysterectomy or primary radical hysterectomy.

Methods: Between January 2010 and December 2015, all patients with diagnosis of locally advanced cervical cancer referred to the Division of Gynecologic Oncology of the affiliated cancer hospital of Xiangya School of Medicine. 93 patients were included in our study, including 23 patients received primary surgery(PS), 32 patients were treated with NACT, and 39 patients underwent NACRT. The indication for adjuvant treatment was limited to the following pathological high-risk factors: pelvic lymph node involvement, parametrial infiltration, and a compromised surgical margin.

Results: Among 93 patients, the disease relapsed in 19 patients, and 21 died. On the whole series, 5-year overall survival(OS) rate was 77.4%, and 5-year recurrence-free survival rate was 70.6%. Univariate analysis revealed that treatment before surgery, stage, lymph node metastasis and effectiveness of preoperative adjuvant treatment were the factors predicted recurrence and mortality(P<0.05). Multivariate Cox proportional analysis revealed that lymph node metastasis was an independent prognostic factor. On survival analysis of preoperative adjuvant treatment and primary surgery, 5-year overall survival rate of preoperative adjuvant treatment group was significantly lower in patients who received radical surgery directly (P= 0.013)

Conclusions: In this retrospective study, locally advanced adenocarcinoma cervical cancer patients who received radical surgery directly had a relatively better OS than those who received preoperative adjuvant treatment.

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The Clinical Value of HPV E6/E7 mRNA to Predict Progression of Cervical LSIL

Xiaobo Zhang1, and Danhua Shen1. 1Peking University People’s Hospital

Objective: To describe the natural history of low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade I (LSIL/CIN1), and to analyze the predictive values of HPV E6/E7 mRNA, p16INK4a and Ki-67 for LSIL/CIN1 outcome, To explore HPV E6/E7 mRNA detected by RNAscope method whether has high clinical application value.

Methods: From January 2013 to January 2016, 102 patients were diagnosed with LSIL/CIN1 by colposcopy-assisted biopsy and were followed up at 1-year intervals at Peking University People’s Hospital. We measured expression levels of biomarkers p16INK4a and Ki67 to predict the outcome of LSIL. We used Spearman correlation statistical analysis to explore the relationships to HPV E6/E7 mRNA, p16INK4a and Ki-67 expression in the different prognosis groups of LSIL/CIN1. According to HPVE6 / E7, Ki-67, P16 and follow-up results of the relationship, the ROC curve was plotted, their areas under the curve were >0.7, indicates that all three have certain application value in predicting the prognosis value of LSIL.

Results: HPV RNAscope score varies from 0 to 4 as shown, the Spearman correlation coefficient was 0.228 and the P value was 0.021, indicating that there was a statistically significant difference in the different prognosis groups. The area under the curve of Ki - 67 was 0.861, which was the largest, the area under the curve of HPVE6 / E7 was 0.808, the area under the curve of P16 was 0.787, All the three area were>0.7. It indicates that all three indicators have certain application value in predicting the prognosis value of LSIL.

Conclusions: HPV E6/E7 mRNA can be used as one of the prognostic indicators for LSIL. The combined application of HPV E6/E7, P16 and Ki67 tests can provide clinicians with important predictive information. RNAscope method has high sensitivity, specificity, and may has high clinical application value.

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Utility of the Second Excision of Atipic's Transformation Zone in Patient with Residual Edge and Injury Recurrence

Leopoldo Tinoco1, Angelo Nicolalde1, Diana Tinoco2, Sonia Carrillo3, Ramiro Tinoco2, and Veronica Chavez4. 1Hospital Oncológico "SOLCA"Quito, 2Hospital IESS QUITO SUR, 3Institute of ginecology and mastology "GINECOMAST", 4Hospital oncológico SOLCA IBARRA

Objective: Determine the convenience of REEZTAT as an auxiliary procedure.

Methods: It is a descriptive epidemiological studies of cases collected between 2008 and 2018 at the “ONCOLOGICAL HOSPITAL SOLCA” QUITO-ECUADOR; evidencing 51 cases diagnosed and treated.

Results: 31 were by the edge with residual neoplasia and 20 by recurrence. Residual neoplasm: 17 carcinoma (CA) in situ, 1 ADENOCARCINOMA IN SITU, 9 CIN III, 2 invasive carcinoma, 1 CIN I, 1 CIN II, REEZTAT.-19 chronic cervicitis (CC), 7 CIN I, 2 CIN II, 3 CIN III. Recurrence: 1 ADENO IN SITU, 3 CA IN SITU, 1 LEIOMYOMA, 2 persistent CIN I, 3 CIN II, 10 CIN III, REEZTAT 15 CC, 4 CIN II, 1 CIN I.

Conclusions: REEZTAT is an option to be considered as a complement to EZTAT that present residual exocervical or endocervical borders, and in recurrent lesions. The technical facility makes it a procedure of choice, except in late menopausal's patients because the tissue atrophy.

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ZNF582 DNA Methylation as a Biomarker for Cervical Adenocarcinoma Detection and Prognosis Monitoring

Nayiyuan Wu1, Jing Wang1, Yu-Ligh Liou2, and Xiaoyun Zhang1. 1Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 2Xiangya Medical Laboratory, Central South University,

Objective: This study aimed to investigate the role of ZNF582 gene methylation in cervical adenocarcinoma (AC) detection, treatment, and prognosis.

Methods: This is a retrospective study of 219 paraffin-embedded cervical tissue blocks. All samples were collected to determine the DNA methylation level of ZNF582. Prognoses of these patients were tracked.

Results: A receiver operating characteristics (ROC) curve was generated to obtain the best cut-off values. Sensitivity and specificity for ZNF582 were 0.60 and 0.93 respectively. The ZNF582 gene showed a higher methylation level in the cervical adenocarcinoma group than in the hyperplasia group. Methylation levels of ZNF582 were reduced in concomitant chemo-radio-therapy (NCRT) patients compared with non-concomitant chemo-radio-therapy patients. Patients positive for ZNF582 methylation have better prognoses.

Conclusions: Aberrant high methylation of ZNF582 may be a potential biomarker of cervical AC detection and prognosis monitoring.

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Colposcopy

Agreement Between Colposcopic Impression and Histological Diagnosis of CIN After Short-Term Training in Inner Mongolia

Mingzhu Li1, Yue Wang1, Chao Zhao1, Hong Tao2, Danhua Shen1, Yuligh Liou2, and Lihui Wei1. 1Peking University People's Hospital, 2Institute of Clinical Pharmacology, Central South University

Objective: To investigate the agreement between colposcopic impression and histology after short-term training for patients with abnormal cytology and/or positive human papillomavirus (HPV) testing who were referred for colposcopy in the inner Mongolia.

Methods: The targeted colposcopy training were conducted by two colposcopists for about 4 -6 hours by showing the image after applying acetic acid and lugol’s solution using electronic colposcope and biopsies were taken from the abnormal areas (acetowhitening or worse, low grade or worse, high grade or worse) as well as from a random (normal) site in case of normal colposcopy impression among 152 women in Tongliao city in the inner mongolia.

Results: Overall sensitivity and specificity between colposcopic impression and histology after short-term training was 45.4% and 89.1% of high-grade impressions. Classification of acetowhitening or worse impressions showed the highest agreement; The sensitivity and specificity of trainee after training of high grade lesion were 66.7% and 94.1% when rating high-grade impressions.

Conclusions: Targeted short-term colposcopy training would be effective in remote areas. Inaccurate colposcopic impressions are more likely to occur in the impression of normal or low-grade lesions, especially for those postmenopausal women, while those in the impression of higher-grade lesions are less likely to be missed.

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Effect of Pregnancy on Regression of Abnormal, High-Grade Cervical Cytology

Lauren Griebel1, Mary Duarte Thibault1, Ali McGregor2, and Kimberly Gecsi1. 1University Hospitals, 2Magee Women's Hospital

Objective: To quantify the proportion of women with regression of high-grade cervical cytology after pregnancy.

Methods: Retrospective chart review of women seen for colposcopy in a resident-run, urban, Medicaid-based clinic at a tertiary care center (University Hospitals) with cytology indicative of high grade lesions (HSIL, or LSIL r/o ASC-H) from February 2013 - October 2017. Primary outcome was percentage of patients who showed postpartum regression of pap cytology or histology after biopsy. Regression was defined as antepartum cytology of HSIL, ASC-H, LSIL-H with negative or LSIL postpartum cytology, or negative or CIN1 biopsy. Secondary outcomes included the number of patients with persistent high grade lesions postpartum, those lost to follow up, and effect of delivery mode on postpartum regression.

Results: Among the 76 women with antenatal results, 40 (53%) had postpartum follow-up. Thirty-six (47%) women without follow-up were of similar demographics, age, and antepartum cytology. The study population was 96% African American and 25+/-4 years old. Of the 76, 59 (78%) underwent vaginal delivery while 16 (21%) underwent Cesarean delivery (delivery data unavailable for one patient). Twenty-two (50%) women showed postpartum regression. Of those, delivery mode had no statistically significant impact on regression rates (p = 0.3). Of the women in this cohort, only 27 (35%) sought follow up after delivery.

Conclusions: Typical regression rates in the literature for a similarly aged cohort range from 30%-50% over 15 weeks to 2 years. Our high regression rate of 50% would suggest that pregnancy and delivery may increase the likelihood of regression.

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Key Determinants of the Value of Random Cervical Biopsy at Colposcopy

Robert Pretorius1, Jerome Belinson2, Raoul Burchette1, Ruifang Wu3, and You-Lin Qiao4. 1Southern California Permanente Medical Group, 2Medworks, Cleveland, OH, 3Peking University Shenzhen Hospital, 4Cancer Institute/Hospital Chinese Academy Medical Sciences

Objective: Determine whether lower proportions of cervical intraepithelial neoplasia (CIN) 2, CIN 3, or Cancer (CIN 2+) diagnosed by random cervical biopsy are from lower cutpoints for an abnormal colposcopic impression or obtaining single random biopsy when colposcopic impression is normal.

Methods: We compared colposcopy experiences within Shanxi Province Cervical Cancer Screening Study (SPOCCS) I, II (N=1,383) and in Shenzhen Cervical Cancer Screening Trial (SHENCCAST) II (N=631).

Results: Proportion of CIN 2+ diagnosed by random biopsy in SPOCCS I, II (33.0%, 141/403) was higher than SHENCCAST II (17.9%, 34/190, p<.001). Quadrant-specific Receiver Operating Characteristic curves for diagnosis of CIN 2+ by colposcopic impression in SPOCCS I, II and SHENCCAST II were similar; a lower cutpoint for an abnormal colposcopic impression resulted in lower proportion of CIN 2+ diagnosed by random biopsy in SHENCCAST II. Normal colposcopic impression was found in 85.1% (120/141) of cases of CIN 2+ diagnosed by random biopsy in SPOCCS I, II and in 58.8% (20/34) of such cases in SHENCCAST II. Of CIN 2+ diagnosed by random cervical biopsy with normal colposcopic impression, 1 cervical quadrant was involved with CIN 2+ in 66.7% (80/120) of colposcopies in SPOCCS I, II and 80% (16/20) of colposcopies in SHENCCAST II.

Conclusions: Colposcopy series with lower proportions of CIN 2+ diagnosed by random biopsy have lower cutpoints for abnormal colposcopic impression and have a single random biopsy when colposcopic impression is normal. To exclude CIN 2+, we advise random biopsy in all cervical quadrants with normal impression.

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LSIL Diagnosed by Colposcopy-Directed Biopsy With HSIL+ Lesions Undetected

Long Sui1, and Fengyi Xiao1. 1Fudan University

Objective: We aimed to explore factors involved in high-grade squamous intraepithelial lesion (HSIL) + not being detected by colposcopy-directed biopsy (CDB).

Methods: We retrospectively reviewed 2427 cases diagnosed by CDB as low-grade squamous intraepithelial lesion (LSIL). After loop electrosurgical excision procedure (LEEP), 2023 cases were confirmed as LSIL (group A), while 393 cases were further diagnosed as HSIL (group B), 6 as squamous cell carcinoma (group C), and 5 as adenocarcinoma (group D).

Results: The patients were significantly older (P = 0.000) in group D (47.6 ± 4.0), C (41.5 ± 4.9) and B (39.7 ± 8.2) as compared with group A (37.6±8.4). CDB detected endocervical glandular involvement (EGI) in 0.35% (7/2023) cases in group A, 0.51% (2/393) in group B, and none in group C and D (P = 0.964). LEEP found 2.1% (41/2023) cases of EGI in group A, which was significantly less (P = 0.000) than the 54.7% (217/393) cases in group B, 33.3% (2/6) cases in group C, and 100% (5/5) cases in group D. CDB detected 8.6% (173/2023) cases with multicentricity in group A, 13.2% (52/393) in group B, 16.7% (1/6) in group C, and none in group D (P = 0.024). LEEP detected 9.2% (186/2023) cases with multicentricity in group A, which was significantly less (P = 0.000) than the 56.7% (223/393) cases in group B, 66.7% (4/6) cases in group C, and 20% (1/5) cases in group D.

Conclusions: Older age, but not EGI and multicentricity in LSIL cases diagnosed by CDB are indicative of HSIL+ lesions.

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Persistence of Inflammatory Immune Response Following Frictional Fabric Cervical Biopsy

Neal Lonky3, Arthur Sitelman1, and Justin Diedrich2. 1Integrated Pathology Laboratory, 2UC Riverside, 3University of California, Irvine

Objective: Minimally invasive colposcopic biopsy using frictional fabric abrasion and tissue removal yields diagnostic cervical specimens with one prior series showing a persistent plasma cell and lymphocyte inflammatory immune response (1). We sought to investigate tissue effects in casae following colposcopy employing frictional biopsy brushes who subsequently underwent LLETZ excision.

Methods: Following IRB approval (IRBCO, Buena Park, CA), we retrospectively reviewed cases that underwent colposcopic frictional brush ectocervical and endocervical biopsy followed by therapeutic large loop electrosurgical excision of the transformation zone (LLETZ) for historical and anatomic pathological evidence of the presence of an inflammatory immune reaction at the biopsy sites.

Results: We reviewed 14 cases where colposcopic biopsies were followed by a LLETZ excision. There were 12 cases with complete documentation. Six of 7 cases where LLETZ followed colposcopy within 30 days showed evidence of a persistent robust inflammatory immune response under the biopsy sites. We noted the inflammatory infiltrate dissipated after 30 days in the 5 remaining cases.

Conclusions: This study confirms a prior report of an immune response following frictional curettage of epithelium into superficial stroma using frictional brushes with further information regarding the time period such an effect persists. Such brushes trap excavated tissue yields diagnostic biopsy specimens and shows persistent anatomic evidence of an immune response at the biopsy site(s). The immunogenicity and therapeutic benefit deserves future studies regarding cell mediated or a humoral response. Future comparison studies of conventional versus frictional biopsy can be evaluated for longitudinal regression of cervical neoplasia as well. (1) Clark BD, Golembeski CP. Observation of a Robust Immune Response Following Frictional Fabric Biospy During Colposocpy. J Lower Gen Tract Dis. 2014;18: S22.

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Risk Factors of Progressing to Cervical Cancer in Women With CIN3 Diagnosed by Cervical Biopsy

Li Geng1, Yanjie Wang1, Yanli Guo1, Ke You1, and Yi Li1. 1Peking University Third Hospital

Objective: To compare the pathological results of colposcopy-guided biopsies and cervical conization performed later in the same patients with cervical intraepithelial neoplasia 3 (CIN3) and to explore factors influencing the accuracy of colposcopy biopsy.

Methods: Patients who underwent colposcopy-guided biopsies and diagnosed with CIN3, from January 2014 to August 2018 in Department of Gynecology of Peking University Third Hospital were included. They were treated with cold knife conization within 2 months. Endocervical curettage were performed before or during conization. Age, cytological abnormalities, HPV infection status, colposcopy findings, pathological results of cervical conization were collected. Data were compared between the progress group(pathology progressed to cancer) and the control group(pathology remained the same).

Results: In all, 550 patient aged 19 -73 years were included(mean age 40.2±10.6). 34 patients (6.2%) were found to progress to cervical cancer after conization, including 32 squamous cell carcinoma and 2 adenocarcinoma. 23 of the cancer patients(67.6%) had wild lesions (CIN3 involved ≥3 quadrants) while 30% of the control group had wild lesions(p<0.001). 9 of the cancer patients (26.5%) were with positive internal conization margin while 4% in the control group(p<0.001). 13 of them(38.2%) had positive endocervical curettage results(pathology CIN3) and 9% in the control group(p<0.001).

Conclusions: The results suggest that CIN3 involved ≥3 quadrants, positive internal conization margin, positive endocervical curettage results were all risk factors of pathology progress to cancer among biopsy-proved CIN3 patients.

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Risk of Recurrence for Women Treated for CIN 3/AIS of the Cervix as Determined by Subsequent Pap Smear Results

Rachel Kupets1, Nathaniel Jembere2, and Li Wang2. 1Toronto-Sunnybrook Regional Cancer Center, 2CancerCare Ontario

Objective: To determine risk of recurrent cervical dysplasia after local ablative treatment (LEEP, LASER, CONE) for CIN 3/AIS predicted by subsequent Pap smear results performed in the first 3 years post treatment.

Methods: Utilizing administrative data from cancer and cervical cytology registries as well as physician billing data for procedures in Ontario, Canada, we identified all women with a diagnosis of CIN 3 or AIS from 2006-2010 and determined their recurrence rate 1- 5 years post treatment defined as a biopsy finding of CIN 3/ AIS or retreatment (LEEP, Laser, Cone, Hysterectomy).

Results: 19,453 women underwent treatment for CIN 3/AIS. Overall, 8.92% recurred. Mean time to recurrence was 927 days. Post treatment risk of recurrence with 1, 2, or 3+ normal Pap results is 7.8%, 6.1% and 6% respectively; recurrence with 1, 2 or 3+ low grade paps (LSIL, ASCUS) is 12%, 22% and 33% respectively. Logistic regression was carried out to determine odds of recurrence post treatment. Factors associated with increased risk include age decile above 21-29, subsequent Pap abnormality, low grade or high grade as compared to a normal pap result. Two normal pap smear results have the same protective effect as 3 or more normal pap results. Treatment modality did not impact recurrence rates. (Table one)

Table

Table

Conclusions: Post treatment Pap smears provide information on risk for recurrence and can inform subsequent screening frequency as well as discharge planning from colposcopy. Addition of HPV testing post treatment can help determine risk of recurrence further.

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The Clinic Significance Study of Colposcopy in the Screening and Diagnosis of Cervical Cancer With HPV 16/18 Infection

Ruiyu Wang1, and Mingrong Xi1. 1West China The Second Hospital

Objective: Due to the late application of HPV vaccine in China, HPV16 and 18 still pose great harm to Chinese women. And colposcopy is a centerpiece of diagnostic tools for women with abnormal cervical screening test results. So, this essay is emphasis on investigate the usage of colposcopy, especially making a distinction between HPV 16/18 positive and other HPV infection in cervical diseases.

Methods: The clinic data of 880 patients who had colposcopic inspections with or without cervical biopsies in West China Second University Hospital between December 2015 and February 2016 were retrospectively analyzed with cervical biopsy results as the standard. 207 specimens of them were infected with HPV 16 or 18. The sensitivity, specificity, positive predictive value, negative predictive value, false positive rate and false negative rate in diagnosing precancerous lesions of cervical cancer were calculated.

Results: The rate of cervical biopsy after colposcopic inspections in all people in sample is 58.9%; and the sensitivity, specificity, false positive rate, false negative rate of electronic colposcopy for cervical precancerousdisease and invasive carcinoma were 90.4%‚43.1%‚56.9%‚9.5%respectively. Compare to HPV 16/18 infection group the rate of cervical biopsy is 72.2%; the sensitivity, specificity, false positive rate, false negative rate were 85.3%‚19.3%‚80.7% respectively.

Conclusions: In HPV 16/18 positive cervical disease, it has lower sensitivity, low specificity and high false positive rate. This may have something to do with fear of missing diagnosis. It adds unnecessary harm to the patient. Colposcopy among HPV 16/18 positive people in western China is still a challenge. It's necessary to enact the guidelines based on big data analysis of Chines people’s samples and conduct operation training.

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The Diagnostic Value of Colposcopy Using Deep Learning for Cervical Squamous Intraepithelial Lesions

Chunnv Yuan1, Yeli Yao1, Xinyu Wang1, Bei Cheng1, Yifan Cheng1, Xinjun Ma2, Jian Wu2, Weiguo Lu1, and Xing Xie1. 1Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China., 2Zhejiang University, Hangzhou, 310027, China.

Objective: Colposcopy guided cervical biopsy is the golden standard for diagnosing cervical cancer and precursors. An accurate diagnosis of colposcopy depends mainly on the experience of the examiner, while it takes a long time to train a qualified colposcopist. Computer assisted diagnosis using artificial intelligence is known as a scientific, accurate and time-saving way to cope with clinical data. The application of deep learning to colposcopy would establish a novel colposcopy technique to replace conventional colposcopy to meet the needs of population-based cervical cancer screening.

Methods: Totally 9803 acetic images and 9756 iodine images from colposcopy were collected. With final pathologic diagnosis as golden standard, lesions were labeled via marking along the lesion border. Replaced with ResNet-34 as its encoder to extract features better, a U-Net model and an FPN model were established respectively to segment the location and predict the rank of suspicious lesions through deep learning. The relevant indexes were calculated.

Results: Through pre-experiment, the recall to predict suspicious lesions in acetic images and iodine images were 85.87% and 87.28% respectively. Importantly, the recall to confirm normal areas reached 92.27% in acetic images and 94.62% in iodine images. Among these suspicious lesions, the recall for the FPN model to predict HSIL was 55.57% and 57.85% in acetic and iodine images respectively. As for LSIL, the recall was 56.16% in acetic images and 60.71% in iodine images.

Conclusions: The model our study established can help doctors sufficiently extract suspicious lesions under conventional colposcopy, safely exclude normal areas, and effectively ease the screening burden.

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HPV Diseases

A Clinical Control Study of Qingdu Suppository in Treating Cervical High Risk Human Papillomavirus Infection

Jiaoying Lou1. 1Dongfang Hospital of BUCM

Objective: To explore the clinical efficacy of Chinese medicine Qingdu Suppository in the treatment of Cervical High-Risk Human Papillomavirus infection.

Methods: There were 90 patients of cervical HR-HPV infection selected from the Dongfang Hospital of Beijing University of Traditional Chinese Medicine, since August 2009 to January 2011. The patients were randomly divided into three groups: the Qingdu Suppository (A compound Chinese Medicine) treatment group, the Andafen(Recombinant Human Interferon α2b in Suppository Form)control group and the observation group(Blank group), which were observed for 3momths. HCII was used to detect the changes of HPV-DNA content (virus load), and the clinical symptoms and signs were statistically analyzed. To evaluate the clinical efficacy of Qingdu Suppository in treating cervical HR- HPV infection.

Results: Both Qingdu Suppository and Andafen can effectively reduce the HPV-DNA viral load, and the cure rates of three groups were 36.7%, 23.3%, and 16.7%, respectively, the total effective rates were 60.0%, 53.3%, and 30.0%.There were statistical differences in the self-control results of the two drug groups after treatment (P < 0.05), showed no significant difference with each other(P>0.05), and both of them had significant difference with the observation group (P<0.05).

Conclusions: Qingdu Suppository can reduce cervical high-risk human papillomavirus (HR-HPV) infection in viral load.

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Assessing Variations in Trends in Incidence Rates in HPV-Associated and Non-HPV Associated Vulvar Cancer

Sarah Simko1, Mona Saraiya1, and Jacqueline Mix1. 1Centers for Disease Control

Objective: In the United States, an average of 3,934 vulvar cancer cases are diagnosed each year (1). Human papillomavirus (HPV) cause 70% of vulvar cancers (2). Few studies have examined incidence of vulvar cancer by HPV-associated status. We aimed to describe incidence rates (IR) and trends among HPV-associated (HPV-V) and Non-HPV associated (non-HPV-V) vulvar cancer cases.

Methods: We used publicly available US Cancer Statistics covering 97% of the US population (2001-2015) to calculate age-adjusted IR (per 100,000 persons) of vulvar cancer, standardized to the 2000 US population. Microscopically confirmed invasive vulvar cancers were grouped according to ICD-O-3 histology. IR were estimated by age (<50 years, 50+) and race/ethnicity. Trends were examined by calculating annual percent change (APC) using SEER*Stat.

Results: There were 2,701 cases of HPV-V in 2001, which increased to 4,001 cases in 2015, with a significant APC of 1.4%. The rate for Non HPV-V decreased 0.5% per year. The IR for HPV-V was higher than non-HPV-V overall (1.9 vs 0.4), among women aged <50 (0.6 vs 0.1) and women 50+ (5.4 vs 1.2). The IR of HPV-V was greater than that of non-HPV-V in the following racial groups: White (2.2 vs 0.4), Black (1.5 vs 0.1), American-Indian/Alaska-Native (1.6 vs 0.2), and Hispanic (1.3 vs 0.3), but was similar in Asian/Pacific-Islanders (0.4 vs 0.3).

Conclusions: HPV-associated vulvar cancers are increasing most likely due to changing sexual behaviors and increased HPV exposure. The HPV vaccine can protect future generations from HPV-associated vulvar cancers.

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Dysregulation on the Lipidic Metabolism Contribute to Cervical Premalignant Lesion Development

Maria Carolina Valença Rygaard1, Fernanda Silva Medeiros2, George Tadeu Nunes Diniz2, Maria Luiza Bezerra Menezes3, Stefan Welkovic2, and Norma Lucena-Silva2. 1IMIP/UNICAP, 2Institute Aggeu Magalhães, 3Health Center Saúde Amaury de Medeiros (CISAM)

Objective: To investigate obesity contribution on cervical lesion development, we studied the body metrics and serologic markers for lipidic and glycemic metabolism in women with benign and low and high grade cervical lesion.

Methods: From a prospective cohort of women attended at the Cervical Pathology Ambulatory of IMIP hospital and CISAM Health Center in Recife, northeastern Brazil, 185 women with diagnosis of cervical lesion by colposcopy and cytology, that gave formal consent, were studied. (National Ethical clearance CAAE:51111115900005190). Patients were weighed and measures of height, waist, brachial and thigh-femoral circumferences were noted. Body mass index was calculated, and serum levels of cholesterol (total, HDL and LDL), triglycerides and glycose were evaluated. Patients were classified as having benign (n=47), low (n=25) or high (n=113) grade cervical lesion. The analysis of continuous variables distribution was using ANOVA or Kruskal-Wallis, and comparison between groups was performed using multinomial logistic regression, considering P≤0.05 significant.

Results: The distribution of body metrics and serological molecules levels among studied groups did not reached a significant difference. Nevertheless, the logistic regression revealed women with increased ratio of total cholesterol per HDL (P=0.051) are at 15-folds high-risk to develop low-grade, but not high-grade cervical lesion (P=0.772) in comparison to those presenting benign lesion. Missing data may have limited a broader statistical analysis.

Conclusions: Despite no effect of obesity on the cervical lesion severity was observed, we showed that dysregulation on the lipidic metabolism may contribute to premalignant lesion development, therefore, health education on dietary may help women at high-risk.

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Frequency of HPV Genotypes in Cervical, Vulvar and Anal HSIL

Prakash Bhuyan4, Mark Einstein1, Robert Edwards2, Céline Bouchard3, Kim Kraynyak4, Mary Giffear4, Tamara Howard4, Bridgette White4, Ashley Santo4, li liu4, Matthew Morrow4, Lindsey Nowak4, Timothy Herring4, ShuPing Yang4, and Mark Bagarazzi4. 1Rutgers New Jersey Medical School, 2Magee Womens Hospital of UPMC, 3Laval University, 4Inovio

Objective: HPV-16 is associated with cervical, vulvar and anal HSIL more than any other oncogenic HPV type. We describe the HPV typing observed in screening samples from the ongoing studies of VGX-3100, a HPV-16 and HPV-18 specific immunotherapy.

Methods: Cervical and vulva biopsy samples were obtained from a Phase 3 study in women with cervical HSIL and a Phase 2 study of women with vulva HSIL, respectively, and anal samples were obtained from a Phase 2 study of HIV negative men and women with anal HSIL. Cervical spatula and brush samples in ThinPrep media (n=156), vulva tissue (n=27), and anal lesion tissue (n=16) from subjects with histologically-confirmed HSIL were analyzed using qualitative PCR. HSIL was confirmed by two blinded pathologists.

Results: 22 different HPV genotypes were detected in cervical samples; the four most frequent were HPV-16 (63.5%), HPV-52 (14.7%), HPV-31 (10.3%), and HPV-18 (9.0%). Seven different HPV genotypes were identified in vulvar HSIL samples; the two most frequent were HPV-16 (70.4%) and HPV-33 (11.1%). Seventeen different HPV genotypes were identified in anal HSIL samples; the five most frequent were HPV-16 (50.0%), HPV-51 (31.3%), and HPV-31, HPV-58 and HPV-6 (all 3 detected at 25%).

Conclusions: HPV-16 is the predominant genotype in screened subjects with anogenital HSIL. However, the virologic profile does differ between these conditions. This could be influenced by biases of subject selection for these trials. This information will be helpful in guiding the development of HPV-specific non-surgical therapies.

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HPV 16/18 Genotypes and Histological Follow-Ups of Negative Cytology and Positive HPV in China's Largest Women Hospital

Xiang Tao1, Li Wang1, Hao Zhang1, Jianan Xiao1, Lihong Zhang1, Xianrong Zhou1, Juan Li2, Long Sui1, and Chengquan Zhao3. 1Obstetrics and Gynecology Hospital of Fudan University, 2Jinan Maternity and Child Care Hospital, 3Magee Women Hospital of UPMC

Objective: To study the HPV 16/18 positive rate for women with negative Pap cytology and positive cobas HPV results and the histological follow-up findings in the largest women hospital in China.

Methods: A retrospective department database search was conducted to identify patients with negative cytology and cobas HPV testing results from 2011-1 to 2018-6.

Results: A total 131707 women with negative Pap cytology and cobas HPV testing results were identified during the study period. Overall Cobas high risk HPV positive rate was 14.0% (18423/13707). Of 18423 cytology-negative/cobas HPV-positive cases, HPV16 was detected in 3302 cases (17.9%), HPV18 in 1137 cases (6.2%), both HPV16 and 18 in 112 cases (0.6%). HPV16/18 positive rate was 24.7%. Histological follow-up findings within 6 months were found in 6575 women with cobas HPV-positive/cytology-negative results. CIN2+ (CIN2 and above) lesions were diagnosed 15.2% in HPV16 positive cases, significantly higher than 3.9% in HPV18 positive cases and 3.0% in other 12 HPV type-positive cases.

Table

Table

Conclusions: This is one of the largest routine clinical practice reports of HPV16/18 genotyping and histological follow-up findings for women with negative Pap test. HPV16/18 positivity accounts 24.7% cases with positive cobas HPV testing. CIN2+ lesions were detected much higher in HPV16 positive case than in HPV18 or other 12 type positive cases. Our study supports ASCCP guideline–HPV 16/18 genotyping triage option and indicates enhanced risk stratification of HPV positive/cytology negative women with HPV 16/18 genotyping in testing. This is the first report of the application of this option in a routine clinical practice setting in China.

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HPV Prevalence Among Males and Females in a Nationally Representative Survey, United States, 2013-2014

Rayleen Lewis1, Troy Querec2, Mariela Scarbrough2, Julia Gargano3, Elizabeth Unger2, and Lauri Markowitz3. 1Synergy America, Inc. and NCIRD, CDC, 2NCEZID, CDC, 3NCIRD, CDC

Objective: Evaluation of population-based HPV prevalence can provide important information on HPV epidemiology. We previously reported any HPV and high risk (HR) HPV prevalence, by sex and age group, in the United States. In this analysis, we extend investigations to include evaluation of quadrivalent vaccine (4vHPV) types.

Methods: We evaluated HPV prevalence overall and by sex and age group (18-24, 25-29, 30-39, 40-49, and 50-59 years), using data from U.S. National Health and Nutrition Examination Survey, 2013-2014. Self-collected penile and cervicovaginal swabs were tested by PCR for 37 HPV types. Prevalence of any HPV, any 14 HR, and 4vHPV types were estimated for 1757 males and 1985 females. We compared males to females using prevalence ratios (PR) with 95% confidence intervals (CI).

Results: Prevalence of any HPV among males and females was 45.2% and 39.9% (PR=1.13, 95% CI 1.04-1.24); HR HPV, 25.1% and 20.4% (PR=1.23, 95% CI 1.09-1.39); 4vHPV, 8.5% and 5.5% (PR=1.54, 95% CI 1.09-2.16). Sex differences varied by age; any and HR HPV were lower among males than females in 18-24 year-olds, but similar or higher at older ages. Findings for 4vHPV were similar although differences by sex were significant only in the oldest age group.

Conclusions: Overall prevalences of any HPV, HR HPV, and 4vHPV were higher in males than females. Variation by age group might be due to sex differences in the natural history of HPV infection and/or sexual behavior. Data on HPV prevalence across age groups can further inform vaccination policy and vaccine impact monitoring.

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Interobserver Variability Study of Pathologists in Diagnosing Anal Squamous Intraepithelial Lesions-With and Without p16

Uma Krishnamurti1, Ashley Monsrud2, Mohammad Mohammad1, Mario Mosunjac1, Gabriela Oprea1, Krisztina Hanley1, Talaat Tadros1, Lisa Flowers1, and Marina Mosunjac1. 1Emory University, 2Morehouse School of Medicine

Objective: This study was conducted to investigate interobserver variability and p16 utility in accurately grading anal squamous intraepithelial lesions (SIL) which is challenging.

Methods: Six pathologists first evaluated only the hematoxylin and eosin slides (H&E) from 146 consecutive anal biopsies (57 with p16 and 89 without p16) and rendered a diagnosis of No SIL (NSIL), low grade SIL (LSIL/AIN 1) or HSIL (AIN 2 and AIN 3). Subsequently, they reviewed both the p16 immunostained and H&E slides and rendered a diagnosis of NSIL, LSIL/AIN 1, or HSIL (AIN 2 or AIN 3). Fleiss kappa values were calculated for the three groups as shown in the results table and for a 4 tier diagnosis (NSIL, AIN1, AIN2, AIN3); 3 tier diagnosis (NSIL, LSIL, HSIL); 2 tier diagnosis (No HSIL, HSIL).

Results: There is only moderate agreement with a 4 tier diagnosis with or without p16. There is substantial agreement when AIN2 and AIN3 are pooled as HSIL both in cases where p16 was used and where it was not required. There is almost perfect agreement with a 2 tier diagnosis in cases where p16 was used when required and also where p16 was not required.

Table

Table

Conclusions: This study shows the importance of a judicious use of p16 for diagnosis. Interobserver agreement was substantial to almost perfect when there is no need for p16; however, when its use is indicated but not reviewed, agreement is much lower even with a 2 tier diagnosis. p16 use where needed will ensure diagnostic accuracy and best possible patient care.

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With the Move to HPV Primary Screening, Will HPV Associated Myths & Stigmas Stop Women Attending Their Pap (Smear) Test?

Robert Music1. 1Jo's Cervical Cancer Trust

Objective: Previous research by leading charity Jo’s Cervical Cancer Trust repeatedly showed low understanding of cervical cancer risks by not attending screening. With many countries moving to HPV testing it commissioned research to understand how women 1. would feel if told they had HPV, 2. understood how it can be contracted, 3. knew their risk of contracting & 4. knew the link between HPV and cancer. We also wanted to test myths and misconceptions, understand the psychological impact of being told they have HPV and feelings about the new HPV test.

Methods: In August 2018 2,034 UK representative women answered a range of questions to gauge knowledge of HPV as outlined in the background.

Results: Many stigmas associated with HPV were found including: shame, fear and promiscuity, low numbers were aware HPV is a virus or is linked to cancer. Main answers:

  • 39% worried what people thought of them if told they had HPV
  • 42% would worry their partner was unfaithful,
  • 68% would be scared if told they had HPV
  • Two-thirds would worry they had cancer
  • 35% have no idea what HPV means
  • 66% would worry it would impact for the rest of their life.
  • 95% didn’t know HPV can be contracted via protected vaginal sex
  • Just 15% thought HPV was common
  • 32% unaware of the link to cervical cancer

Conclusions: Significant numbers lack understanding about HPV, perpetuating stigmas and myths. With programmes worldwide moving to HPV testing millions more women will be told they have HPV. It’s essential there’s a reduction in anxiety surrounding the virus to ensure women fully understand their results and not put off attending screening. Increased education is vital to normalise HPV. A multi-centred approach is needed via general public awareness campaigns and improved training amongst health professionals who will be having more HPV related conversations with patients.

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HPV Screening and Management

Analyses of the Onclarity HPV Assay’s Performance in Cervical Specimens Collected With Broom vs Brush/Spatula

Karen Yanson1, Salma Kodsi1, Miriam MAncuso2, Stephanie Taylor2, Aaron Ermel3, Jim Williams3, Kenneth Fife3, Stephen Young4, Edward Hook5, Devin Gary1, Laurence Vaughan1, Weimin Zhang1, Jeff Andrews1, and Barbara Van Der Pol5. 1Becton Dickinson, 2Louisiana eState University Health Science Center, 3Indiana University School of Medicine, 4Tricore Reference Laboratory, 5University of Alabama at Birmingham

Objective: To compare the BD Onclarity™ HPV Assay performance in BD SurePath™ specimens collected with an endocervical broom versus an endocervical brush/spatula.

Methods: A total of 33,858 women were enrolled in a multicenter study to evaluate the performance of the BD Onclarity HPV Assay. Endocervical specimens were collected using either a broom or brush/spatula. Human beta globin (HBB) cycle threshold (Ct score), HPV Ct score, and high-risk HPV positivity rates were analyzed in the intended use populations (ASCUS ≥ 21 years, NILM ≥ 30 years, primary screening ≥ 25 years) and age groups (21-24, 25-29, 30-39, 40-49, and 50+).

Results: There were 1953 subjects in the ASCUS, 22284 subjects in the NILM, and 29512 subjects in the primary screening population. The HBB data showed a significant difference in mean Ct scores between devices across populations and age groups (except 50+) (p <0.0001-0.0002), however the actual difference was relatively small (0.31 to -0.19). No evidence of collection device HPV Ct score difference (-0.15 to 0.25) was found when stratified by population or age groups (p= 0.5238-0.8636). HPV positivity rates also showed no significant difference across populations and age groups (p= 0.1182-0.9721). Positivity rates decreased with increasing age independently of the collection device.

Conclusions: The data show the two devices have similar HPV positivity rates, HPV and HBB Ct scores when stratified across populations and age groups. These results indicate that either collection device may be used in all intended use populations with the BD Onclarity™ HPV Assay.

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Changes in Cervical Cancer Screening Among Women With Precancerous Cervical Lesions in 5 US Sites, 2008-2015

Angela Cleveland1, Julia Gargano1, Delaney Dean1, Marie Griffin2, Melissa Powell3, Nancy Bennett4, Ina Park5, Linda Niccolai6, Elizabeth Unger1, and Lauri Markowitz1. 1CDC, 2Vanderbilt University Medical Center, 3Oregon Health Authority, 4University of Rochester School of Medicine and Dentistry, 5UCSF, 6Yale School of Public Health

Objective: We describe trends in human papillomavirus (HPV) test utilization preceding diagnosis of precancerous cervical lesions during a time of changing screening recommendations in the United States.

Methods: We analyzed data on women aged 21-39 years diagnosed with cervical intraepithelial neoplasia grade 2 or higher (CIN2+) identified through population-based surveillance in five U.S. locations. Screening history was abstracted from medical records, and classified as cytology+HPV, cytology only, HPV only, or unknown. We used the Cochran Armitage test to evaluate trends in screening tests among two screening-eligible age groups (21-29, 30-39 years), and Chi-square to examine HPV test utilization by cytology results.

Results: From 2008–2015, CIN2+ was identified in 16,041 women (n=9,487 21-29, n=6,554 30-39). The use of an HPV test, either as adjunct with cytology or as primary screen, increased from 36.2% in 2008 to 64.7% in 2015 (p<0.001); testing increased in both age groups (21-29: 31.9% to 54.3%, p<0.001; 30-39: 44.3% to 74.4%, p<0.001). In 2015, most screening was cytology+HPV (63.7%); use of HPV test alone was rare (1%). Adjunctive HPV testing varied by cytology results for both age groups (p<0.001, Table). For example, among 21-29 year-olds, 23.6% of LSIL and 91.5% of ASCUS cytology had an HPV test. Over half (n=2,248/3,874) of HPV tests in 21-29 year-olds were among cases with ASCUS.

Conclusions: Increasingly, the cervical cancer screening method leading to detection of CIN2+ includes HPV testing. Trends in screening, methods, and population screened, need to be considered when interpreting trends in CIN2+.

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Clinical Performance of a New Hybrid Capture Based HPV Assay With HPV16/18 Genotyping

Hongsheng Lu1, Yingzhi Yu1, and Lili Chen1. 1Taizhou Central Hospital (Taizhou University Hospital)

Objective: This study was aimed to evaluate the clinical performance of DALTONbio DH3, a Chinese HPV detection technique based on hybrid capture with HPV16/18 genotyping, in cervical cancer screening.

Methods: The cases with Pap cytology and HPV test from September 2017 to October 2018 in Taizhou Central Hospital, Zhejiang, China were analyzed. High risk HPV test were performed by using DALTONbio DH3 HPV assay (Hangzhou DALTON BioSciences, Ltd. China)for 14 types of HR-HPV. LBP(Guangzhou Anbiping Medical Science Technology Co., Ltd. China) was used for Pap test. Women with positive DH3 HPV test and ASC-US or worse cytology would be referred to colposcopy.

Results: Totally, 7791 women with all the results including HPV, cytology and histological findings were included and analyzed. hr-HPV positive rate was 13.04%, while HPV 16/18 types were detected in4.16% cases. The sensitivity, specificity, positive and negative predictive value of DH3 to detect CIN2+ were 98.1%, 87.5%, 5.1% and 100%, respectively. In comparison, the corresponding results of cytology test were 88.7%, 93.3%, 8.3% and 99.9%. Additionally, the corresponding results of HPV16/18 were 52.8%, 96.2%, 8.6% and 99.7%.

Conclusions: Compared with cytology test, high-risk HPV test, DH3 is highly sensitive for the detection of cervical precancerous lesions. DH3HPV assay with HPV16/18 genotyping may provide a useful tool for cervical cancer screening in Chinese rural areas.

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Comparison of Cervical Cancer Screening Between Self-Sampling and Clinician-Sampling by FQ-PCR and Cobas 4800

Jingran Li1, and Lihui Wei1. 1Peking University People’s Hospital

Objective: To comparison the effectiveness of human papillomavirus (HPV) detection of vaginal self-sampling and clinician-sampling by fluorescence quantitative PCR and Cobas 4800 for cervical cancer screening, and to explore the new model of cervical cancer screening.

Methods: 1 101 eligible women aged 25~65 years were recruited in Tongliao area of Inner Mongolia by Peking University people's hospital from August 28 to 29, 2017, conducting cervical cancer screening by vaginal self-sampling and clinician-sampling. Fluorescence quantitative PCR was used to detect 15 high-risk HPV subtypes in vaginal self-sampling and clinician-samples. Fourteen high-risk subtypes were detected by using the Roche Cobas 4800 HPV DNA method, and genotyping of HPV16 and HPV18. Women with HPV16/18, or other 12 types of HPV positive and cervical liquid based cytology ASC - US or above referred into colposcopy examination and biopsy, compare the coincidence rate, sensitivity, specificity, positive and negative predictive value.

Results: Among 1 101 women, the HPV positive rate of self-sampling by fluorescence quantitative PCR was 17.44% (192/1 101), and that of clinician-sampling was 16.35% (180/1 101). The coincidence rate between self-sampling and medical HPV testing was 97.28% (1 071/1 101), among which 9 cases (0.82%) were negative for self-sampling and positive for medical sampling, and 21 cases (1.91%) were positive for self-sampling and negative for medical sampling. The positive rate of HPV in clinician-sampling by Cobas was 14.82% (163/1 101).The coincidence rate of HPV positive was 95.91% (1 055/1 101) between the two methods, and the difference was not statistically significant (P >0.05). 55 cases colposcope examination and biopsy, the detection rate of CIN1, CIN2/3 and cervical inflammation was 49.09% (27/55), 23.64% (13/55) and 27.27% (15/55). The sensitivity of the detection CIN2/3 in two sampling were 100%, the specificity was 83.33% and 90.48%, respectively. The distribution of high-risk HPV types detected by self-sampling and clinician-sampling was consistent. The top 5 were HPV52, HPV16, HPV58, HPV18 and HPV31, respectively.

Conclusions: The detection of human papillomavirus in vaginal self-sampling has a high conformance rate with clinician- sampling, which can be used for cervical cancer screening.

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Comparison of Results From the Onclarity HPV Assay for Prequot Versus Postquot SurePath Clinical Samples

Salma Kodsi1, Devin Gary1, Stephen Young2, Aaron Ermel3, Jim Williams3, Kenneth Fife3, Edward Hook4, Barbara Van Der Pol4, Ronald Luff5, Mohammad Al-Ghoul6, Stephanie Taylor7, Catherine Cammarata7, Laurence Vaughan1, Jeff Andrews1, Karen Yanson1, and Valentin Parvu1. 1Becton Dickinson, 2Tricore Reference Laboratory, 3Indiana University School of Medicine, 4University of Alabama at Birmingham, 5Quest Diagnostics, 6Center for Disease Detection, LLC, 7Louisiana State University Health Science Center

Objective: To compare results from the BD Onclarity™ HPV Assay (Onclarity) with BD SurePath™ (SurePath) specimens prior to cervical cytology sample processing (Prequot) and after processing (Postquot) to enable testing flexibility in screening approaches.

Methods: Samples from 3879 consecutive subjects in the Onclarity trial were tested. 0.5 ml of SurePath media was aliquoted prior to cytology processing (Prequot). The SurePath vial was then processed on the BD PrepMate™ and after processing, 0.5 ml of the residual specimen was transferred to an Onclarity diluent tube (Postquot). The Prequot and Postquot samples were tested using the BD Viper™ LT system with Onclarity. The results were evaluated based on both subject age and cytology classification.

Results: Onclarity results from Prequot versus Postquot are presented in Table 1. The overall percent agreement is as follows: ASC-US (≥21 years) was 98.5% (95% CI: 95.8%, 99.5%), >ASC-US (≥21 years) was 98.1% (95% CI: 93.3%, 99.5%), NILM (≥ 30 years) was 98.3% (95% CI: 97.8%, 98.8%), and all subjects (≥25 years) was 98.1% (95% CI: 97.6%, 98.5%).

TABLE 1

TABLE 1

Conclusions: The overall agreement of Onclarity results from Prequot and Postquot samples for each of the subject populations was above 95%. These results establish that both sample types are appropriate for HPV testing using Onclarity in cervical cancer screening populations.

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Detection of Low-Grade Squamous Intraepithelial Lesions: Value of Molecular, Cytologic, and Histologic Evaluation

Stephanie Skala1, Emily McMullen1, Lili Zhao1, Girume Degu1, Heather Walline1, Richard Cantley1, and Richard Lieberman1. 1University of Michigan

Objective: Management protocols for abnormal cervical cytology and/or high-risk human papillomavirus (hrHPV) have been refined based on long-term follow-up. Although colposcopy and directed biopsies help determine management, diagnostic reproducibility for biopsy diagnosis of low-grade squamous intraepithelial lesions (LSIL) is poor to fair. Proper biopsy classification aids risk stratification and provides feedback regarding colposcopic findings.

Methods: Patients underwent cervical biopsies (2013-2017) resulting in benign or LSIL diagnoses. Cytology (Pap) diagnoses, hrHPV screening, and biopsy diagnoses were recorded (n=88). HPV multiplex PCR-MassArray and L1 consensus PCR evaluated presence of high and low-risk HPV in the biopsy tissue (“ground truth”). Four pathologists rated morphologic features (anisonucleosis, chromatin and nuclear envelope irregularity, binucleation, nucleoli, surface maturation, inflammation, basal hyperplasia, mitotic activity, keratohyalin granules, dyskeratosis). Agreement (kappa) was calculated for each feature and diagnosis.

Results: Agreement for diagnosis of LSIL was fair (kappa=0.30). Agreement was lowest regarding nucleoli (K=0.01) and nuclear envelope irregularity (K=0.14), and highest for inflammation (K=0.53). The area under the receiver operating characteristic curve (AUC) for age, Pap, and HPV screening was 0.54. Anisonucleosis, nuclear irregularity, binucleation, absence of inflammation, and mitotic activity were significantly associated with HPV in biopsy tissue based at least one rater’s assessment. Leave-one-out prediction models demonstrated that morphologic assessment of biopsies improves our ability to predict the presence of HPV in biopsy tissue (Table 1).

Table

Table

Conclusions: Morphologic assessment of biopsy tissue, Pap, and HPV screening are useful for diagnosis of LSIL. Agreement about the diagnosis of LSIL and presence of relevant features is suboptimal. Morphometric analysis is underway to help us to understand how we should adjust our approach to diagnosis of LSIL.

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Evaluation of an Isothermal Amplification HPV Detection Assay for Primary Cervical Cancer Screening

Wei Zhang1, Ruifang Wu1, Hui Du1, Jerome Belinson2, Chun Wang1, Xia Huang1, and Bin Yang3. 1Peking university Shenzhen Hospital, 2Preventive Oncology International, Inc. Cleveland Heights, USA and Cleveland Clinic, Women’s Health Institute, 3Cleveland Clinic, Department of Anatomic Pathology

Objective: To evaluate the performance of the Ampfire HPV assay using both self and clinician collected samples for cervical cancer screening.

Methods: 1941 women in a population based screening had both the self-collected and clinician collected samples tested with the Ampfire, Cobas and SeqHPV assays. Clinician samples also had cytology. Ampfire is an fast (1.5h) isothermal amplification detection assay that detects 15 high risk HPV types (includes HPV 53) directly from raw samples in a single tube reaction and genotypes HPV 16 and 18 simultaneously with real time fluorescent detection. Cobas is PCR based for 14 high risk HPV types (16, 18, pool of 12) and SeqHPV is a next-gen sequencing assay for 14 separate HPV types common to all three assays. Colposcopy and biopsy done if positive on any assay (self, directed, or cytology).

Results: Mean age 42.8. CIN 2+ (1.44%).Concordance of Ampfire to Cobas (self/clinician) 98.25% (Kappa=0.88) and 98.56% (Kappa=0.90) respectively; concordance Cobas self/clinician 97.73% (Kappa=0.85).

Table

Table

Conclusions: When Ampfire HPV was applied for CIN2+, it showed similar sensitivity, specificity, PPV, and NPV on both self- and clinician-collection (P>0.05). Ampfire HPV and Cobas HPV (P>0.05) have similar performance with both specimen types.

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Evaluation of Different Triages for HPV Primary Cervical Cancer Screening –-A Cross-Sectional Study in China

Ling Li1. 1Jiangxi Maternal and Child Health Hospital

Objective: To explore optimal triage strategies of HPV primary screening for China's rural areas.

Methods: A population-based organized cervical cancer screening in 7 counties in rural areas from Oct. 2014 to Jan. 2016. The positive women of HPV primary screening was triaged by liquid based cytology (LBC), Pap Smear, HPV16/18, HPV loads (VL) and visual inspection with acetic acid and lugol’s iodine (VIA/VILI) respectively. We compared the strategies above by index of sensitivity, specificity, referral rate et al to ≥ HSIL for the final pathology result as the gold standard.

Results: There were 17,782 women with complete data in the study, HPV infection rate was 13.56% (2412/17782). The colposcopy referral rate of the triage strategies with LBC, Pap Smear, HPV16/18, HR-HPV viral load VIA/VILI were 4.5%, 2.8%, 2.8%, 6.6% and 3.7%, respectively. The sensitivity to HSIL+ were 65.8%, 51.9%, 86.8%, 73.3% and 41.7%, respectively. The specificity to HSIL+ were 69.8%, 81.0%, 85.8%, 52.2% and 65.3%, respectively. The number of times of referral colposcopy was only 1 time by HPV16, 18, HPV load or VIA/VILI triage, the average pathological diagnosis time were 9.2 days. There was twice and 15.5 days by Liquid based cytology test (LBC) and conventional Pap cytology test (Pap Smear).

Conclusions: Concerned about present situation and adaptability of cytological diagnosis in the China’s rural areas, triage with HPV16/18 or HPV load for hrHPV-positive women appear to be the most feasible management strategies in rural areas in China.

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HPV-Negative High-Grade CIN: A Case Report

Li Min Lim1, Ida Ismail-Pratt1, Diana Lim1, Benedict Yan1, and Jeffrey Low1. 1National University Hospital

Objective: Persistent infection with high-risk genotypes of the human papillomavirus (HPV) has been shown to be a precursor to cervical intraepithelial neoplasia (CIN) and cancer. The International Agency for Research on Cancer has categorized 12 mucosal HPV types as being carcinogenic to humans. HPV genotyping assays approved by the United States Food and Drug Administration (FDA) include the detection of 14 high-risk HPV genotypes including the 12 carcinogenic types. While these assays are known to have high negative predictive value, we aim to contribute to current literature by describing a case of HPV-negative high grade CIN.

Methods: This is a case a report describing a case of CIN2 diagnosed in a tertiary institution in Singapore with negative HPV genotyping results using an FDA-approved HPV test.

Results: A 36 year old lady underwent co-testing using the Roche cobas® 4800 HPV test and liquid-based cytology. The HPV test was negative and the cervical smear showed high-grade squamous intraepithelial lesion (HSIL) encompassing moderate dysplasia. Colposcopy was performed, confirming CIN2 on punch biopsy for which she underwent laser cone excision and endocervical curettage. Subsequent genotyping using a non-FDA approved assay identified the presence of HPV 67, currently categorized as being possibly carcinogenic.

Conclusions: While there has been a gradual move towards primary HPV screening, clinicians should be aware that current HPV genotyping assays do not include all the high-risk HPV subtypes that are potentially carcinogenic. This results in a small proportion of high-grade CIN which may be missed although the frequency is very low.

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Hr-HPV Subtype Prevalence in Rural Zimbabwe in HIV-Positive and HIV-Negative Women

Megan Fitzpatrick1, David Katzenstein1, Zvavahera Mike Chirenje2, Kathy McCarty2, and Benjamin Pinsky1. 1Stanford Hospital, 2Zimbabwe

Objective: High-risk human papilloma viruses (hr-HPV) subtype distribution is critical to understand for screening and vaccinations, especially among HIV positive women and in low-resource settings.

Methods: hr-HPV screening and subtype analysis was performed in a community-based project in rural Zimbabwe, as well as focused visual inspection and cytology (Pap smears).

Results: hr-HPV prevalence was 17% (105/618); 34% (39/115) vs. 13% (66/503) among HIV-1-positive and -negative participants, respectively (p=9.0e-08). HPV 35 was detected most frequently (20%) while an equal percentage of HPV16, HPV18, HPV52, and HPV 68 were detected (16%).

Conclusions: HPV 35 was the most prevalent hr-HPV subtype, which is a type not included in existing vaccines (bivalent or 9-valent) and led to precancerous lesions in our study. Duration of ART decreases the overall hr-HPV infection rates, but not the likelihood of a precancerous lesion by cytology.

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Negative Pap Cytology and Positive HPV Tests by Cervista and Aptima Assays: Genotype and Histologic Follow-Ups

Chengquan Zhao1, Min Han1, Michelle Stram1, Juan Li1, Kavita Verma1, and Huina Zhang1. 1Magee-Womens Hospital, UPMC

Objective: To evaluate the prevalence of HPV 16/18 subtypes and their correlation with subsequent histologic findings in women with negative cervical cytology and positive high risk HPV (Pap-/hrHPV+) test.

Methods: We identified 3064 women with Pap-/hrHPV+ test results from June 2013 to June 2018 through a retrospective institutional data base search. Subsequent HPV genotype testing results were documented in 2866 women, among whom 543 also had histologic follow-ups within 6 months. HPV testing and genotyping was performed using Cervista assays from June 2013 to May 2015, and using Aptima assays from June 2015 to now.

Results: HPV16 and/or 18 (45) were detected in 17.5% of women with Pap-/hrHPV+ results. Compared with the Cervista group, the Aptima group had a lower percentage of HPV 16 (p <0.01) and a higher percentage of HPV 18/45 (p <0.01). During follow-ups within 6 months, CIN2 and above lesions (CIN 2+) were detected in 11.8% of HPV 16/18 (45) positive patients, and in 3.0% of other hrHPV positive patients (p=0.02) in the Aptima group. The Cervista group had lower CIN 2+ rates overall. CIN1 detection rate was similar between HPV16/18/45 group and other 12 HPV type group, but was significantly higher in Aptima positive cases than in Cervista positive cases.

Conclusions: When Pap testing was negative, women with HPV 16/18 (45)+ results were more likely to have CIN2+ lesions than women with other hrHPV+ results, supporting current guidelines of immediate colposcopic examination for HPV16/18+ patients. Aptima HPV mRNA testing appeared to have a higher positive predictive value for CIN2 + and CIN1 lesions than Cervista HPV DNA testing. Table. HPV genotyping and histological follow-up findings in women with Pap-/hrHPV+ results using Cervista and Aptima HPV tests

Table

Table

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Onclarity HPV Assay Reproducibility When Using SurePath Preservative Fluid for Detection of High-Risk HPV Types

Devin Gary1, Karen Yanson1, Salma Kodsi1, Aaron Ermel2, Jim Williams2, Kenneth Fife2, Stephen Young3, Edward Hook4, Barbara Van Der Pol4, Valentin Parvu1, Jeff Andrews1, James Harris1, and Laurence Vaughan1. 1Becton Dickinson, 2Indiana University School of Medicine, 3Tricore Reference Laboratory, 4University of Alabama at Birmingham

Objective: Reproducibility of results by replicate, by operator, by lot, or over time, can be used to assess agreement of diagnostic results. Here, reproducibility of the BD Onclarity™ HPV Assay (Onclarity—performed on the BD Viper™ LT System) was assessed.

Methods: Three test sites were each provided nine, identical, ten-member panels prepared in BD SurePath™ media. Panels included contrived specimens (spiked with HPV 16, 18, or 45 DNA—each at high negative, low positive, and moderate positive concentrations) and pooled clinical specimens (prepared close to clinical cut-off) that were positive either for HPV 16, 18, 31, 33/58, 45, 52, or HPV(-). Panel members were tested in triplicate; tested 2X/day; tested by two different operators over nine days; and tested using three different reagent lots. Reproducibility was measured by instrument-generated versus expected result for contrived specimens, and mean cycle threshold (Ct) for clinical panels.

Results: 156-159 results were generated for each panel member. Contrived, low and moderate positive specimens demonstrated ≥ 94.0% and ≥ 98.0% concordance with the expected results, respectively. For the high negative specimens, HPV 18 and 45 were in 100%, while HPV 16 specimens were in 90.6%, agreement with the expected results. The HPV(-) pool generated no false positives. Ct values from pooled clinical samples revealed high reproducibility by variable; consistent across genotypes (Table 1).

TABLE 1

TABLE 1

Conclusions: Onclarity was highly reproducible between test sites, reagent lots, and test runs using either contrived or pooled HPV positive clinical samples. The qualitative and quantitative results reported here met acceptance criteria.

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Primary HPV Screening With Integrated HPV16/18 Genotyping Performs Well in Women ≥25: Onclarity Trial Baseline Data

Mark Stoler1, and Thomas Wright2. 1University of Virginia Health System, 2Columbia University

Objective: Current ACS guidelines recommend a hybrid screening approach involving cytology with HPV triage for women 21-29 and cotesting for women 30-65. HPV primary screening is often compared to this hybrid approach for women 25-65. Data from the Onclarity trial were analyzed to determine the clinical performance of these two strategies in terms of risk values for ≥CIN2 and ≥CIN3—as well as colposcopy rate for identification of high grade cases in women ≥25.

Methods: BD SurePath™ cytology and HPV detection was performed on 33,858 enrolled subjects during routine screening. Hybrid Capture 2 (HC2) HPV testing was also performed on a second sample. 5,534 subjects were referred to colposcopy/biopsy and provided evaluable histology specimens. Prevalence, performance, and risk values for ≥CIN2 and ≥CIN3 were determined from biopsy specimens.

Results: HPV prevalence was 12.7%. HPV 16/18 prevalence within CIN2 and ≥CIN3, respectively, was 28.5% and 54.3%. HPV testing had verification-bias adjusted ≥CIN3 sensitivity (69.5%) and specificity (92.3%) values similar to HC2. Cytology alone had sensitivity and specificity values of 57.7% and 94.2%, respectively. Using Onclarity, primary screening with HPV 16/18 (partial genotyping) resulted in performance values at least as robust as those obtained through the hybrid screening algorithm (Table). Partial genotyping resulted in a colposcopy rate of 6.1%, compared to 6.2% for hybrid screening.

TABLE

TABLE

Conclusions: Onclarity is clinically validated for primary screening in women ≥25 years. Compared to the hybrid strategy, partial genotyping (16/18) actionably stratifies this screening population for robust performance values without increases in colposcopy rate.

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Progression/Regression/Treatment Results of HPV Infection & CIN in a Population-Based Cervical Cancer Screening Program

Xinfeng Qu4, Yongmei Zhang1, Ping Zhou1, Huanxia Zhong1, Zhang Lin2, Guozheng Hu2, Haina Guo1, Guoli Sun1, Jingdong Ye2, Yutao Du2, Lihui Wei3, and Jerome Belinson4. 1Dongguan Women and Infants Hospital, 2Shenzhen BGI Corporation Ltd, 3Peking University People's Hospital, 4Preventive Oncology International Inc.

Objective: To retrospectively evaluate the progression/regression and treatment results of HPV infections, and CIN.

Methods: 252,650 women were screened over a 3-5-year interval in 2 runs by Dongguan Cervical Cancer Screening Program (DOCCS). Data from 109,410 (participants in Run 2) were evaluated by comparing their test results to their results in Run 1.

Results: Of the 109,410 participants, 6.25% (6,833) and 5.21% (5,685) were positive and 93.8% (102,577) and 94.8% (103,725) were negative for HPV in Run 1 and Run 2, respectively (p=1.0). 4,451(65.14%) of the 6,833 women positive for HPV in Run 1 regressed to be HPV negative in Run 2, leaving 34.85% (2,283) who tested as HPV+ in Run 2. Of the 90 patients who were diagnosed as CIN1 in Run 1, 73 (81.11%) tested as HPV- in Run 2, 17 (18.89%) remained HPV+. No patient had persistent low grade CIN or progressive disease. Of the 274 CIN 2/3s in Run 1, 241 (87.96%), most of whom received treatment, tested HPV-; 33 (12.04%) continued to test HPV+. One patient had low grade CIN (0.36%) and 1 persistent high-grade disease in Run 2.

Conclusions: Repeated cervical cancer screening in this population-based program did not significantly decrease the HPV infection rate. However, with appropriate management the prevalence of pre-invasive lesions decreases significantly, therefore preventing 99.6% of the potential cancers. A 3-5 year screening interval is effective for cancer prevention. Positive management is the key but adds considerable complexity to an organized program.

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Single Infection of HPV16 Is Associated With a Higher Risk of Cervical Cancer and CIN3 Than Multiple Infection

Li Geng1, Yanli Guo1, Ke You1, Yi Li1, and Xuefei Ge1. 1Peking University Third Hospital

Objective: To compare the cervical cancer and CIN3 detection rate between women with HPV16 single infection and multiple infection.

Methods: A total of 5280 women who were screened at Peking University Third Hospital were recruited. All the recruited women had no cervical biopsy or treatment history. The median age was 29 (19-80). The liquid based cytology (Hologic Thinprep), high-risk HPV test (Roche Cobass4800), colposcopy and cervical biopsy were applied in all women.

Results: 4770 women were HPV positive and 510 were HPV negative. 833 women were HPV16 single infection and 661 women were HPV16 multiple infection. Women with HPV16 single infection were more likely diagnosed as cervical cancer and CIN3 than those with HPV16 multiple infection [53/833 (7.0%) vs 17/661 (2.6%), p<0.05; 184/833 (22.1%) vs 116/661 (17.5%), p<0.05]. 197 women were HPV18 single infection, 8 (8/197, 4.1%) of them were diagnosed as cervical cancer and 6 (6/197, 3.0%) were diagnosed as CIN3. 163 women were HPV18 multiple infection, 2 (2/163, 1.2%) of them were diagnosed as cervical cancer and 6 (6/163, 3.0%) were diagnosed as CIN3. 510 women were HPV negative, 10 (10/510, 2%) were diagnosed as cervical cancer and 5 (5/510, 0.20%) were diagnosed as CIN3.

Conclusions: Women who had HPV16 single infection were more likely diagnosed as cervical cancer and CIN3 than those who had HPV16 multiple infection.

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The Clinic Significance Study of HPV 16/18 L1 Capsid Protein Using in the Screening and Diagnosis of Cervical Cancer

Ruiyu Wang1, and Mingrong Xi (Qie)1. 1West China Second University Hospital

Objective: Cervical cancer is the most common gynecologic tumor of genital duct which threats women's health and life. Due to the late application of HPV vaccine in China, HPV16 and 18 still pose great harm to Chinese women. L1 capsid protein is the main capsid protein of HPV. The expression of L1caspid protein will change while the progression of HPV infection improves. So, this essay is to explore the expression and clinical significance of HPV L1 capsid protein in cytologic specimens of the cervix with HPV 16/18 infection.

Methods: The detection of HPV L1 protein, by using immunocytochemical method, was performed on 144 patients with hpv16/18 infection who visited the clinic of West China Second University Hospital from November 2017 to February 2018, as well as 20 patients in the control group with negative HPV and cytologic inflammatory response. The results of L1 protein detection were compared with the results of cervical cytology and biopsy results. The sensitivity, specificity, positive predictive value, negative predictive value, false positive rate and false negative rate of in diagnosing precancerous lesions of cervical cancer were calculated.

Results: The L1 capsid protein positive expression rate of chronic cervicitis cases‚CIN I‚CIN II‚CIN III‚ICC were 88.9%‚68.8%‚33.3%‚9.1%‚7.1% respectively. The L1 capsid protein negative expression rate of chronic cervicitis cases‚CIN I‚CIN II‚CIN III‚ICC were 11.1%‚31.3%‚66.7%‚90.9%‚92.9% respectively.

Conclusions: In HPV 16/18 positive cases, HPV L1 capsid protein expression positive rate in cytological specimens of the cervix is decreased with cervical lesion progression. This method is expected to be a means of assisting diagnosis and diversion.

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The Tumorigenicity of HPV58 in Chinese

Ruifang Wu1, Hui Du1, Jingjing Shen1, Chun Wang1, Wei Zhang1, Jerome Belinson2, and Xinfeng Qu2. 1Peking University Shenzhen Hospital, 2Preventive Oncology International Inc.

Objective: To explore the tumorigenicity of important HPV types in Chinese.

Methods: 1547 Chinese women were co-tested with a HPV genotyping assay and cytology. 208 women with CIN3+ (14 cancers and 194 CIN3 patients) are included in this analysis. The number of CIN3+ among each individual HPV type and the proportion of each individual genotype detected among the CIN3+ cases were analyzed. The odds ratios (OR) for the important HPV types were calculated.

Results: The 6 most prevalent high risk HPV types in women positive for HPV are, in order of most frequent: 52, 16, 58, 51, 33, and 39. Of the women diagnosed as CIN3+ it included: 34.7% of the HPV16 positives, 20.7% of HPV58 positives, 17.5% of HPV18 positives, 8.9% of HPV52 positives, and 4.5% of the women positive for other types. (p=0.000). HPV16, 58, and 18 were detected in 55.5%, 25.5%, and 10.1% of all the CIN3+ cases respectively. Among the 14 cancers: HPV16 was detected in 8, HPV 16/58 in 1, HPV 58 in 1, HPV 18 in 2, and HPV 52 and 56 each in 1 case. HPV16, 58, 18, 31, 33, and 52 are ranked to be the top 6 in order of OR for tumorigenicity. The OR for HPV16, 58, and 18 are 229.4, 77.5, and 51.8 respectively.

Conclusions: Accounting for more than a quarter of CIN3+ and ranked second in term of OR value, HPV58 is as important as HPV18 in terms of tumorigenicity for cervical cancer in Chinese women.

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Trends of Cervical Cancer Screening and Adherence to New Guidelines in Davidson County, Tennessee Women During 2006-2017

Manideepthi Pemmaraju1, Sheelah Blankenship1, Stephanie Allen1, Edward Mitchel1, and Marie Griffin1. 1Vanderbilt University Medical Center

Objective: We examined changes in prevalence of cervical cancer screening among Davidson County, Tennessee women associated with 2012 guidelines, which recommended no screening for age <21 years and less frequent screening for 21-64 years.

Methods: We identified women ages 18-64 years, enrolled in Tennessee Medicaid (TennCare) 2006-2017, and receipt of screening by Current Procedural Terminology codes indicating Papanicolaou (Pap) smears and Human Papillomavirus (HPV) detection tests. We evaluated prevalence of annual Pap smear (old guidelines) and of less frequent screening as recommended by 2012 guidelines.

Results: Overall, the number of Davidson County women age 18-64 years enrolled in TennCare increased from 27,603 in 2006 to 38,691 in 2017. Percent with annual pap screening declined in all age groups from 2006 to 2017 (figure 1a). Receipt of Pap within 3 years (age 21-64 years) or Pap plus HPV test within 5 years (age 30-64 years) also decreased in all age groups (figure 1b). Screening consistent with these 2012 guidelines declined from 2006 to 2017 in every age group: 77.9% to 61.6% age 21-29 years, 55.4% to 41.3% age 30-39 years, and 37.3% to 24.2% age 40-64 years.

Conclusions: The new cervical cancer screening guidelines were associated with declines in annual Pap screening as recommended. During the period when annual screening was recommended, a relatively high proportion of women were screened at least every 3 years. However adherence to screening every 3 to 5 years as currently recommended has declined substantially for women age 21-64 years.

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HPV Vaccination

HPV Vaccination History and Impact on Colposcopy Outcomes

Neal Lonky1, Diane Da Silva2, Juan Carlos Felix3, Nancy Cannizzaro4, LanFang Xu4, and Chun Chao4. 1University of California, Irvine, 2University of Southern California, 3Medical College of Wisconsin, 4Kaiser Permanente

Objective: Although human papilloma virus (HPV) vaccination is an important aim for effective cervical cancer prevention practice, its impact on colposcopy practice and triage is paramount for predicting its utility. This preliminary report seeks to show associations between vaccination history, lesion grade, and HPV subtype prevalence in a large group colposcopy practice.

Methods: In this IRB approved study, 15 physicians utilized a robust colposcopy data collection tool embedded in the electronic medical record in Kaiser Permanente Orange County. Data including vaccination history, epidemiologic variables, visit type (first, repeat, or treatment visits), colposcopy, and biopsy practice and pathology were recorded. Histological specimens were genotyped (polymerase chain reaction) in cases where CIN 2 or higher-grade cases were identified.

Results: Preliminarily, 870 patients were identified who underwent first, repeat, an/or treatment colposcopy visits from whom 472 were age 21-38 and could have undergone HPV vaccination (nearly all Gardasil 4). 87 patients (mean age 31.5 years) showed CIN 2+ or worse on histology; 29 of 87 cases (33%) documented a history of HPV vaccination prior to colposcopy whose tissue specimens showed HPV 16 in 13 (45%) or HPV 18 in 2 (6.8%). Five of 13 cases (38.5%) harbored HPV 16 in lesions (two CIN 3, three CIN 2), three cases with optimal dosing prior to reported sexual activity onset.

Conclusions: This preliminary report showing the association of HPV vaccination status to colposcopy proven histologic high-grade evidence shows infection with neoplasia can occur. Further analysis of a larger cohort with vaccine subtypes relative to age, sexual history, co-morbidities, vaccine type, pathologic over-read validation and p16 lesional status will also be reported.

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Successful Implementation of a Postpartum HPV Vaccination Program Among Low-Income Women in Texas

Abbey Berenson1, Richard Rupp1, Yong-Fang Kuo1, and Jacqueline Hirth1. 1University of Texas Medical Branch

Objective: New strategies are needed to increase human papillomavirus (HPV) vaccination rates in the US. Postpartum hospitalization is an opportunity to administer the 3-dose series to young women who have not received it. We evaluated a postpartum vaccination program implemented at the University of Texas Medical Branch (UTMB) Galveston Campus.

Methods: Between October 2012 and August 2016, postpartum women ≤26 years old from Galveston County who delivered at John Sealy Hospital were offered the vaccine free of charge prior to discharge or were scheduled for vaccination at a subsequent clinic visit. Follow-up injections were scheduled to coincide with postpartum visits or their infants’ appointments with a pediatrician. Patent navigators sent reminders prior to appointments and rescheduled missed appointments. Data were collected to determine uptake and completion rates.

Results: Prior to implementation of the intervention, only 20% of UTMB’s postpartum patients had initiated the HPV vaccine series. During this program, 2,031 women were approached whose records indicated they were unvaccinated or partially vaccinated. Of these, 185 (9%) stated they had already completed the HPV vaccine series and 385 (19%) declined vaccination. A total of 1,265 initiated the first dose, and 196 who had not completed the series received a subsequent dose postpartum. Of those eligible, 79% received at least 1 dose (1,461/1,846). Overall, 77% (1125/1,461) of women who received a dose postpartum completed the series. In total, 3,532 HPV vaccine doses were distributed through this program.

Conclusions: The postpartum period is an effective time to offer catch-up vaccination to unvaccinated women.

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Innovative Teaching

Initial Lessons From Implementing a Telecolposcopy Program on a High Risk Population in California

David Levitz2, Rachel Steward1, Bonnie Betts1, and Cathy Sebag2. 1FPA Medical, 2MobileODT

Objective: To assess feasibility of live, remote monitoring and preceptorship by experts on colposcopy procedures to trainees seeking colposcopy certification. Of interest are the effects of ongoing mentorship remotely on both patient care and provider proficiency.

Methods: A custom feature was built into MobileODT’s EVA System, a smartphone-based colposcope, utilizing a video-conferencing application. When using this custom feature, an expert connected from her home computer to a live procedure conducted at the clinic. Through screen sharing, the provider at the point of care was able to show the expert a live video feed of the colpsocopy exam and seek guidance. The expert then provided guidance on improved visualization of the cervix, and recommended sites to biopsy. Some video sessions were also recorded in order to enable secondary review of the procedure by additional experts. To date, two providers are undergoing training in this method. Eighteen subjects have undergone colposcopy with remote preceptorship, and more will be recruited. Following the procedure, a satisfaction survey is given to all patients.

Results: Initial findings showed that experts were able to assist the junior providers in colposcopy procedures. Specifically, video quality was deemed sufficient to make clinical decisions and direct sites for biopsy. All patients reacted positively to the live expert supervision.

Conclusions: In this study, feasibility of live telecolposcopy on a mobile, connected colposcope was demonstrated. The current implementation shows promise at enabling experts to reach remote patients, as well as enabling quality assurance of colposcopy procedures.

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Role of Administrative Data in Public Health Surveillance for Cervical Pre-Cancer, Davidson County, Tennessee

Sheelah Blankenship1, Stephanie Allen1, Manideepthi Pemmaraju1, Edward Mitchel1, and Marie Griffin1. 1Vanderbilt University Medical Center

Objective: To demonstrate administrative data utility in improving data completeness for the HPV Vaccine IMPACT Project, a CDC-funded public health surveillance program that monitors the impact of the HPV vaccine on cervical pre-cancers.

Methods: To identify women missed by standard surveillance, we searched three administrative data systems for Davidson County women age 18-39 years with cervical dysplasia diagnoses (International Classification of Diseases codes) and procedures (Current Procedural Terminology codes) in 2013 and 2014. The Hospital Discharge Data System (HDDS), includes data on hospital-based inpatient and outpatient surgical procedures, the Ambulatory Surgery Treatment Center (ASTC) data system includes data on non-hospital outpatient procedures, and the Tennessee Medicaid (TennCare) data system includes data on low-income women. We also attempted to link all women meeting surveillance criteria to TennCare to augment missing vaccination, insurance, and race/ethnicity information.

Results: Through standard surveillance, we identified 794 women with cervical pre-cancer in 2013 and 2014. Using three administrative data systems, we identified an additional 32 (4%) women with cervical pre-cancer (15 HDDS, 7 ASTC, 10 TennCare). Forty-eight percent of women (397/826) were ever enrolled in TennCare; for these women, linkage provided new information on vaccination and insurance status for 20% and race/ethnicity for 19%.

Conclusions: Augmenting standard surveillance with administrative data resulted in a 4% increase in case identification. In addition, linkage with an insurance data system helped minimize missing vaccination, insurance and race/ethnicity information. Administrative data were successful in improving data completeness for HPV IMPACT and may have quality improvement applications for other public health surveillance programs.

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Innovative Technology

Evaluation of Cytology P16 Staining and PAX1 Methylation in the Detection of Cervical High Grade Lesion

Mingzhu Li1, Yuligh Liou2, Jingran Li1, Danhua Shen1, Yun Zhao2, and Lihui Wei1. 1Peking University People's Hospital, 2Institute of Clinical Pharmacology, Central South University

Objective: To determine the effect of cytology P16(PathCINp16) and PAX1 methylation for the detection of high-grade cervical lesion.

Methods: A total of 128 women with abnormal cytology and/or positive human papillomavirus (HPV) testing during primary screening between the ages from 26 to 62 in the Inner mongolia area who were referred for colposcopy in the cervical cancer screening program were analyzed. PathCINp16 and PAX1 methylation detection were applied in all the patients before colposcopy.

Results: 46 patients were negative for intraepithelial lesion or malignancy, 54 patients were cervical intraepithelial neoplasia (CIN) 15 patients were CIN2, 13 patients were CIN3. The sensitivity of cytology P16 was 53.6%, which was more than cytology (33.3%) and PAX-1 methylation (34.4%) and less than HPV testing (100%). The specificity of PathCINp16 was 92%, which was greater than cytology (≥ASCUS) (86.6%) and PAX-1 methylation (86.3%) and HPV testing (5%). Combined parallel testing of PathCINp16 with PAX-1 methylation showed superior sensitivity (0.78 vs. 0.56) and superior negative predictive value (0.92 vs. 0.86) to the combination of Pap smear results and PAX-1 methylation.

Conclusions: Combined parallel testing using cytology PathCINp16 and PAX1 methylation tests may provide better performance than a combination of Pap smears with PAX1 methylation tests in detection for cervical neoplasia.

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Image Registration Between Cervical Images Taken by Two Different Optical Devices

Ilan Landesman1, Effi Levi1, Shiri Gordon1, Oz Seadia1, and Omer Lory1. 1Biopmedical Ltd

Objective: To evaluate image registration between corresponding pairs of cervical images taken by two distinct optical devices that comprise the Biop Colposcopy System (by Biop Medical Ltd.).

Methods: The system consists of a digital colposcope and a micro-colposcope probe. The probe is a multimodal optical device that scans the cervix tissue and collects optical information required to identify High Grade Squamous Intraepithelial Lesions (HSIL). Using a dedicated algorithm, a hot-cold map is produced, describing the probabilities for HSIL. We performed image registration between images acquired by the probe and by the digital colposcope in order to project the probability map on the colposcopy image.

Results: Data from nine participants was collected. Two annotators marked two corresponding sets of 5-8 points of visually distinct landmarks on the images taken by the two optical devices. Based on the registration algorithm, the system predicted locations for these points on the colposcope image. For each of the marked landmarks, registration error is defined as the distance (in mm) between the location marked by the annotators and the location produced by the registration system. The average mean error was 1.20 mm (with a standard deviation of 0.52 mm). The average maximum error was 2.21 mm (with a standard deviation of 1.02 mm).

Conclusions: The results demonstrate the feasibility in registering the cervical images obtained from the micro colposcope probe to the one obtained from the digital colposcope, thus enabling the Biop Colposcopy System to project the predicted probabilities for HSIL onto the latter image.

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Increased Vaso-Vagal Reactions From Cervical Ablative Treatments in Chinese Patients

Jerome Belinson4, Suhui Wu1, Jingfen Sun1, Longhua Hu1, Haixia Shang2, Yaling Huang1, Xinfeng Qu3, Miriam Cremer4, Juan Felix5, Raul Murillo6, and Karla Alfaro7. 1Shanxi Academy of Medical Sciences, Shanxi Dayi Hospital, 2Dayi Hospital of Shanxi Medical University, 3Preventive Oncology International Inc., 4Cleveland Clinic, 5Medical College of Wisconsin, 6Hospital Universitario San Ignacio, 7Basic Health International

Objective: To investigate the occurrence of vaso-vagal reactions in different ethnic populations after cervical ablative therapies.

Methods: Cervical cancer is a leading cause of mortality in low-and middle-income countries. We are currently studying the treatment of high-grade pre-cancerous lesions (CIN2+) by safe, portable and available devices. We are participating in a randomized controlled multicenter clinical study, (supported by NIH UH3CA189883), to compare cure rates of CIN2+ treated with CO2 cryotherapy, CryoPen®, and thermoablation. The effectiveness of the treatment alternatives and the side effects are being evaluated. This interim report examines the occurrence of vaso-vagal reactions to the treatments.

Results: Interim data shows vaso-vagal responses occurred more frequently in Chinese patients. To date 22 of 44 randomly treated patients (50%) had vaso-vagal reactions (flushed face and/or complaints of hot face) during or post treatment at our China site. The symptoms lasted from 5 seconds to 1 hour (13.8 ± 8.5 minutes) and then disappeared without treatment. A few vaso-vagal patients felt slightly dizzy (3/22), palpitations (2/22), nausea (1/22) and asthenia (2/22), also quickly resolving without treatment. By contrast vaso-vagal symptoms occurred 2/111 patients (1.8%) in El Salvador, and 0/27 in Colombia. In China of the 22 with vaso-vagal symptoms, 8 occurred with CO2, 10 with CryoPen, and 4 with Thermoablation.

Conclusions: This interim report suggests that our Chinese patients experience vaso-vagal reactions to ablative cervical treatments at a very high rate compared to the other sites in our study.

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Isothermal HPV mRNA Amplification for Cervical Cancer Screening in Resource-Limited Settings

Kathryn Kundrod1, Chelsey Smith1, Philip Castle2, Kathleen Schmeler3, and Rebecca Richards-Kortum1. 1Rice University, 2Albert Einstein College of Medicine, 3MC Anderson Cancer Center

Objective: This study presents work towards the development of an HPV mRNA test for cervical cancer screening in resource-limited settings. Detection of E7 mRNA overexpression aims to identify progression toward cervical precancer and cancer with high sensitivity and specificity. Here, proof-of-concept work toward an isothermal, quantitative, point-of-care HPV 16 E7 mRNA test is presented.

Methods: Synthetic DNA was used as a standard; mRNA was extracted from SiHa cells and reverse transcribed. Quantification was performed by qPCR; isothermal amplification was performed with recombinase polymerase amplification (RPA). RPA reactions were performed at 37 degrees C for 30 minutes, and amplicons were detected by gel electrophoresis and lateral flow.

Results: Using synthetic HPV 16 DNA, a limit of detection of 100 input copies was demonstrated. Proof-of-concept amplification of E7 cDNA from SiHa cells was also shown.

Conclusions: In its current form, this assay relies on standard laboratory equipment. To translate this test to resource-limited settings, test components will be incorporated into a paper and plastic device, which has previously been demonstrated with RPA [1]. Next steps will include assay optimization and validation with clinical samples. In addition, HPV 18 mRNA detection will be incorporated. A multiplexed HPV 16 and 18 assay will serve as a model for this test, and future work will be required to include detection of all high-risk genotypes. With a fully integrated, paper-based HPV mRNA test, more specific cervical pre-cancer screening could be achieved at a lower cost than with currently available commercial tests. References [1] BA Rohrman and RR Richards-Kortum. Lab Chip. 2012; 12(17):3082-8.

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Multimodal Optical Imaging for Cervical Cancer Screening and Diagnosis — a Feasibility Study

Mark Spitzer2, Shiri Gordon1, Effi Levi1, Oz Seadia1, David Chen1, Yaron Rachamim1, and Ilan Landesman1. 1Biopmedical Ltd, 2Hofstra Northwell School of Medicine

Objective: To assess the ability of a novel multimodal optical imaging device (Biop Colposcopy System) to detect High Grade Squamous Intraepithelial Lesions (HSIL).

Methods: The Biop Colposcopy System is comprised of a digital colposcope and a microcolposcope probe. The probe is a multimodal optical device that scans the cervix and combines information from white light reflected spectroscopy, coherent light scattering and high magnification RGB imaging. An algorithm produces a hot-cold map describing the probabilities for HSIL in the scanned area. This map is projected on an image acquired by the digital colposcope, providing additional information for directed biopsy. Optical data was collected from 18 participants previously scheduled to undergo conization. The study was conducted in the Hungarian Defence Forces Military Hospital and in Szent János's Hospital in Budapest, Hungary. Each participant underwent an optical probe scan followed by standard colposcopy. Up to four abnormal and two additional normal locations were identified for biopsy by colposcopy or by the probe.

Results: Diagnoses were rendered by two pathologists with a level of agreement of 88%. Conflicts were resolved by a third pathologist. The optical data was used for device output training and validation. Data set included 47 HSIL biopsies and 71 non-HSIL biopsies (LSIL and normal). The model was tested using a cross-validation setup. Using only two modalities: white light reflected spectroscopy and high magnification RGB imaging, the sensitivity was 85% with a specificity of 77%. Ongoing investigations look to incorporate coherent light scattering into the model.

Conclusions: The results demonstrate the ability of the Biop Colposcopy System to detect HSIL and its potential to add valuable information to colposcopy.

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Other

Economic and Humanistic Burden of HPV Related Head and Neck Cancers in the United States: A Systematic Review

Smita Kothari2, Carole Mamane1, Mia Malmenas1, Rebecca LeVan2, and Edith Morais3. 1ICON plc, 2Merck, 3MSD

Objective: To collect and synthetize data on Head and Neck Cancer (HNC) costs, and Health-Related Quality of life (HRQoL) estimates using HPV studies from the United States (US).

Methods: A systematic literature review (SLR) was conducted in January 2018. MEDLINE, EMBASE, Cochrane-CENTRAL, EconLit, NHS EED and PsycInfo were systematically searched for cost-effectiveness analyses on nonavalent HPV vaccine, HPV cost studies and HNC HRQoL studies published in English in the last ten years.

Results: Nine US studies were included for evidence synthesis: four cost-effectiveness studies, four cost studies and one HNC psychological impact study. Results are displayed in Table 1. For economic evaluations, HNC cost inputs ranged between $45,000 and $47,378. Costs were related to oropharyngeal cancer and only included direct medical costs. Three recent studies provided cost-data that can be of use for upcoming HPV economic models. In a cost study performed among Texan patients, healthcare costs of oropharyngeal cancer were estimated to be of $139,749. One HRQoL study reported psychological distress in HNC patients (Beck’s Depression Inventory [BDI] score > 10 and Hospital Anxiety and Depression Score [HADS-D] > 7). QoL was affected with radiotherapy, as shown by both increased BDI and HADS scores (Δ5.4 and Δ2.8 respectively; p>0.05).

Conclusions: This SLR identified that HNC have a substantial impact in patients’ quality of life and that in the HPV economic analyses in the US.

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Evaluation of Photodynamic Therapy for Reproductive Tract Precancerous Lesions

Mengzhen Zhang1, Yuehui Su1, Chunyan Zhang1, Wenjing Hou1, Yuligh Liou2, Yueyue Chen1, Ya Xie1, and Rui Hu1. 1The First Affiliated Hospital of Zhengzhou University, 2Central South University; Hunan Key Laboratory of Pharmacogenetics

Objective: Precancerous lesions of the reproductive tract, leukoplakia and HPV have been a possible cause of cancer in women. Although doctors follow up on mild lesions by guidelines, many women can expect simple and convenient treatments to reduce cancer fear and maintain a normal quality of life. The purpose of the studies was to evaluate the efficacy of photodynamic therapy for the reproductive tract precancerous lesions in China.

Methods: Following the GCP guidance, the subjects were recruited in the First Affiliated Hospital of Zhengzhou University in China. The inclusion criteria were female, signed informed consent, with reproductive tract precancerous lesions including CIN (cervical intraepithelial neoplasia), VAIN (vaginal intraepithelial neoplasia) and VIN (vulvar intraepithelial neoplasma). The results of cytology, HPV and colposcopic check were evaluated before and 3-6 months after treatment. One of the positive results and suspicious results were confirmed by histological reports. Treatment efficacy was analyzed in the study.

Results: Two hundred and ten subjects were enrolled in the study and 51 patients who reached complete assessment time were analyzed in the report. Forty-one patients (78.9%) were all negative results by cytology, HPV testing and colposcopy evaluation. CIN-VAIN, CIN-VIN, and vulvar leukoplakia groups were all turning negative 6 months after treatment. The high risk HPV patients were 42.3% turn to undetected.

Conclusions: The current results indicated that the photodynamic therapy is a promising treatment to reduce the time for reproductive tract precancerous lesions.

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Vulvar Syringoma- a Rare Benign Tumor of the Eccrine Vulvar Glands

Anna Dietl1, Ursula Riester2, and Mir Fuad Hasanov3. 1University Hospital Freiburg, 2Institute for Pathology, 3Department of Obstetrics and Gynecology

Objective: In our outpatient clinic a 28-year-old woman presented with a swollen left labia minor and symmetrical papular lesions at both labia majora. As she felt embarrassed for her vulva she has abstained from any recent sexual activity. A biopsy showed a syringoma: ductal structures surrounded by sclerotic stroma in the lower and ducts with two-layer cuboid epithelium in the upper parts. In some ducts the margin wall bulges out to form characteristic small comma-like tails.

Methods: We considered the following therapies: local with antihistamines, corticosteroids, atropine or tretinoin, CO2-laser, excision and reduction of the labia hypertrophy. Given her young age, restoration of a normal female vulva to regain a normal sexual life was seen as important. We hence performed CO2-laser with additional left labiaplasty.

Results: The patient developed a postoperative vulvar edema and wound infection, which was treated with diclofenac suppository and oral antibiotics for five days. When she visited the clinic again six weeks later she was pleased with the results.

Conclusions: Vulvar syringomas need no treatment. It may be provided either to relieve symptoms or for aesthetic reasons. Pruritus does not respond to corticosteroids or antihistamines. CO2-Laser resurfacing is a long-lasting, highly effective-therapy for the relief of pruritus and for resolving the lesions safely and easily. Our case shows that syringoma of the vulva still needs to be considered whenever multiple papular lesions appear after puberty and pruritus doesn’t respond to steroids. Individual therapies should then be discussed with the patient, taking into account age, self-perception, possible pregnancy and preexisting conditions.

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Underserved Populations (Transgender, Homeless, Native American, etc.)

Home HPV Testing as an Alternative Cervical Cancer Screening Method in Women Living With HIV: A Feasibility Study

Anh Nguyen1, Kristen Lee1, and Jenell Coleman1. 1Johns Hopkins University

Objective: Home-collected high-risk HPV (HC-HPV) tests have been shown to be feasible alternatives to increase screening among HIV-uninfected women. Our objective was to investigate the feasibility and effectiveness of using mailed HC-HPV tests as a potential screening tool among women living with HIV (WLHIV).

Methods: WLHIV undergoing routine Pap and HPV testing were recruited from Feb-Oct 2016 at an urban academic gyn clinic. Participants were given HPV (Aptima E6/E7 mRNA) kits to be mailed back to researchers after home-collection. HC-HPV, clinician-collected HPV (CC-HPV; Hybrid Capture 2 DNA), and Pap tests were compared using descriptive statistics and chi square.

Results: 71 participants enrolled, median age was 50 years, 91% were Black, 71% had a smoking history, 95% received antiretroviral treatment, and mean CD4 count was 695. 56 (78.9%) mailed back the HC HPV tests. There was no difference in demographics between participants who returned the HC-HPV tests and those who did not (p>0.05). Of 56 participants who returned the HC-HPV tests, 35 were HC-HPV positive (62.5%), 24 (42.9%) were CC-HPV positive. 3 (5.4%) were HC-HPV negative but had a pap result that would result in a colposcopy (trigger pap) – among them, 1 was CC-HPV positive and 2 were CC-HPV negative (Table 1).

TABLE 1

TABLE 1

Conclusions: Majority of participants returned the HC-HPV tests. False negative rates were low. Mailed HC-HPV tests could be an effective screening tool among WLHIV engaged in care.

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STRIDES: Studying Risk and Improving Disparities in Mississippi — A Collaboration Between UMMC and NCI

Carolann Risley1, Megan Clarke2, Kim Geisinger1, Mark Schiffman2, Laree Hiser1, Mary Stewart1, Lei Zhang3, Maria Demarco2, and Nicolas Wentzensen2. 1University of Mississippi Medical Center, 2National Cancer Institute, 3Mississippi Department of Health, University of Mississippi Medical Center

Objective: Mississippi has among the highest cervical cancer incidence and mortality in the U.S., with apparent racial disparities. Studies are needed to evaluate cervical precancer and cancer in strata of cytology and HPV in this population, and the performance of novel screen and triage strategies in low-resource settings. To address these gaps, we designed a study in collaboration with the NCI evaluating racially-diverse and underserved women undergoing cervical cancer screening.

Methods: Statewide, data from approximately 30,000 women aged ≥21 years with co-testing with Pap and cobas4800 at the UMMC and the MSDH will be collected. Selected residual cytology specimens are being stored for testing with HPV triage markers, including p16/Ki-67, HPV genotyping, and methylation. Records will be followed for at least 5 years with follow-up sample collections; demographic, clinical, co-test, and histopathology data will be obtained through electronic medical record linkage. IRB approval obtained.

Results: As of October 2018, the baseline database includes 9,680 women. Most women (58%) are black, followed by white (26%), and the mean age is 37 years. Overall, 82.6% have normal cytology, and 1.4% have high-grade cytology. Of those with HPV testing, approximately 22% were positive (5% HPV16/18). The prevalence of HPV was significantly higher in Black compared to White women (p<0.0001). Linkage to histopathology data is underway.

Conclusions: Our initial baseline data reflect the high disease burden in this population, indicating potential racial differences in the prevalence of HPV. Prospective data collection will enable risk estimation and assessment of the performance of triage-biomarkers.

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Uterine Cervical Cancer Screening Evaluation in Xingu Indigenous Park

Neila Speck2, Ana Carolina Scopin1, Adhemar Longatto3, Fernanda Tso2, Fernanda Munari3, Julisa Chamorro Ribalta2, Claudia Porto2, Douglas Rodrigues2, and Gustavo Focchi2. 1, 2UNIFESP, 3Barretos Cancer Hospital

Objective: To evaluate 13 years of cervical cancer screening actions and assistance in the Xingu Indigenous Park, through cytological alterations analysis, correlating age and DNA-HPV test.

Methods: This is an observational, transversal and retrospective study conducted by data analysis of screening and control actions of uterine cervical cancer in the scope of the Xingu project of the Universidade Federal de São Paulo (UNIFESP). The population studied consisted of indigenous, sexually active women, aged 11 years or older, belonging to 16 ethnic groups residing in the middle, lower and east Xingu regions. The study was developed with the analysis of the results obtained by conventional cervical screening test (Pap smear) and basic DNA-HPV test.

Results: The population coverage of cytological examination in the period averaged 89.4%. In all actions, there was a higher percentage of normal cytological results. In 2005 and 2010 years, occurred the largest number of cytological alterations, with high-grade squamous intraepithelial lesion (HSIL) and low-grade squamous intraepithelial lesion (LSIL), respectively. Only 3 cases of cervical cancer were documented over the 13 years of follow-up. The HPV positivity rate was 24.5% and latency 22.9%.

Conclusions: In this study, was observed that the high coverage of the population was valuable in maintaining the quality of screening because of the large number of normal exams and rare cases of cancer compared to the national incidence. The extremes of the ages showed a higher percentage of LSIL and HSIL respectively. The basic DNA-HPV test, without genotyping, confirmed a higher percentage of positivity in those who had HSIL.

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Vulvar Intraepithelial Lesions and Neoplasia

Extramammary Paget’s Disease of the Vulva: A Singaporean Perspective

Li Min Lim1, Rachel Lee1, Joseph Ng1, Ilancheran Arunachalam1, Jeffrey Low1, and Ida Ismail-Pratt1. 1National University Hospital

Objective: We aim to identify the current practice and outcomes for women diagnosed with extramammary Paget’s disease (EMPD) of the vulva in a tertiary institution in Singapore and to provide evidence-based recommendations for the management of this condition.

Methods: This is a 5-year retrospective case series conducted in a tertiary institution in Singapore diagnosed from January 2012 to December 2017. All women who were diagnosed with EMPD of the vulva were identified by a computerised coding system.

Results: There were 8 cases of EMPD of the vulva diagnosed. The age of diagnosis ranged from 42 to 84 years. The presenting complaint for half of the patients was vulvar pruritus. Out of the 8 patients, 2 underwent surgical excision, 4 opted for medical treatment with imiquimod and 2 declined treatment. Recurrences were detected in both patients who underwent surgical excision requiring repeat surgeries. All 4 patients who had medical treatment were offered surgery for persistent lesions, out of which 3 proceeded with surgical excision while 1 declined surgery. Screening for concurrent cancers were performed for all patients, detecting invasive ductal carcinoma of the breast in 1 patient and caecal intramucosal carcinoma in another.

Conclusions: This is the largest case series of EMPD of the vulva in Singapore, the management of which is currently controversial. In view of the refractory nature of EMPD of the vulva, surgical treatment should be recommended as first-line and consideration for long-term usage of medical treatment with imiquimod could be a solution to reduce recurrence risks.

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Health Disparities in Louisiana Women: A Population Based Study Analyzing Incidence of Invasive Vulvar Cancer

Crystal Nhieu1, Tammy Dupuy1, Ferney Moore1, and Xiao-Cheng Wu1. 1LSU HSC

Objective: To describe and compare the incidence, age and stage of diagnosis, relative survival and mortality of invasive vulvar cancer in Louisiana as it compares to the national US population.

Methods: Descriptive study analyzing the incidence, mortality and relative survival rates of invasive vulvar cancer in Louisiana from 2000-2014. Data analyzed was from Louisiana Tumor Registry, SEER program and CDC Cancer Registries.

Results: The U.S incidence of vulvar cancer was 2.4 and Louisiana incidence was significantly higher at 2.8 per 100,000 person years (P<0.05). In Central Louisiana, incidence rates for all races was significantly higher than general Louisiana rates (3.6 vs 2.8, P<0.05). In Louisiana mortality rates were significantly lower than national mortality rates (0.4 vs 0.5, p<0.05). White females’ mortality rates were also significantly lower than national mortality rates (0.4 vs 0.5; p<0.05). For females aged <60, Louisiana incidence rates were significantly higher than their national counterparts (30-39 years, 1.6 vs 0.7; 40-49 years, 3.3 vs 2.0; and 50-59 years, 4.5 vs 3.5; p<0.05). 61.6% of the new cases in Louisiana were diagnosed in the localized stage, and 30.1% in the regional stage. The incidence of cases diagnosed with localized (1.7 vs 1.4) and regional cancer (0.8 vs 0.7) are significantly higher than national incidence rates (p<0.05).

Conclusions: Louisiana has higher incidence rates of vulvar cancer as compared to U.S national counterparts. More specifically, Central Louisiana has the highest incidence rate in the state. Although unclear, it is likely secondary to lack of resources and access to a tertiary healthcare system.

Copyright © 2019 by the American Society for Colposcopy and Cervical Pathology