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2016 ASCCP Oral Presentations

Journal of Lower Genital Tract Disease: April 2016 - Volume 20 - Issue 2 - p S1–S9
doi: 10.1097/LGT.0000000000000197
2016 ASCCP Oral Presentation Abstracts
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Towards an International Consensus of Practice Standards in the Detection of Anal Cancer Precursors

Richard Hillman 1,2, Naomi Jay3, Tamzin Cuming4, Mayura Nathan4, Stephen Goldstone4, and Joel Palefsky3. 1Western Sydney Sexual Health Centre, Western Sydney Local Health District, Parramatta, New South Wales 2137, Australia, 2Centre for Infectious Diseases and Microbiology, Westmead Clinical School, University of Sydney, New South Wales 2006, Australia 3UCSF ANCRE Center, Mount Zion Hospital, 1701 Divisadero Street, UCSF, San Francisco, CA 94115 4Homerton Anal Neoplasia Service, Homerton University Hospital, London E96SR, United Kingdom, 4Laser Surgery Care 420 W 23rd St, New York, NY 10011 -on behalf of the International Anal Neoplasia Society.

Objective: Using high resolution anoscopy (HRA), the aim for anal dysplasia service providers is to find the most amount of histologic anal high-grade squamous intraepithelial lesions (HSIL) possible, with the goal of identifying patients at high risk of anal cancer, or treating HSIL to attempt to reduce the risk of progression to anal cancer. HRA is currently provided by a diverse group of professionals from varying backgrounds. We set out to define minimum service standards for anal cytology collection and HRA.

Methods: Experts from North America, Europe and Australasia pooled their clinical expertise and developed provisional guidelines. These were reviewed by the board of the International Anal Neoplasia Society (IANS). Draft guidelines were then sent to the entire IANS membership for comments and the final draft ratified by the board.

Results: The exact nature of an adequate HRA was defined, as were minimum standards of service, required practical competencies and key training components. Quality assurance metrics and minimum standards were established. These will be presented.

Conclusions: Whilst we await the outcomes of several trials to determine the most appropriate algorithms for screening and treatment of anal HSIL, we have developed some provisional metrics for HSIL diagnosis. These will allow professionals to readily compare their practice performance with others. They will also facilitate the interpretation of research data and the development of multicenter, multinational trials focused on HSIL diagnosis and management. The establishment of standards may allow the provision of evidence of competence, that can ultimately lead to formal HRA certification.

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Virologic Correlates Strongly Support the Use of Composite Cytology-Histology in the Diagnosis of Anal High Grade Squamous Intraepithelial Lesions

Richard J Hillman 1,2, Dorothy A Machalek3,4, I Mary Poynten3, Fengyi Jin3, David J Templeton3,5, Carmella Law6, Jennifer Roberts7, Sepehr N Tabrizi4,8, Suzanne M Garland4,8, Annabelle Farnsworth7, Christopher K Fairley9, Andrew E Grulich1, and on behalf of the SPANC study team. 1Western Sydney Sexual Health Centre, Western Sydney Local Health District, Parramatta, New South Wales 2137, Australia 2Centre for Infectious Diseases and Microbiology, Westmead Clinical School, University of Sydney, New South Wales 2006, Australia 3HIV Epidemiology and Prevention Program, The Kirby Institute for infection and immunity in society, University of New South Wales, Sydney, Australia 4Department of Infectious Diseases and Microbiology, Murdoch Childrens Research Institute, Melbourne Australia 5RPA Sexual Health, Sydney Local Health District, Sydney, Australia 6St Vincent’s Hospital, Sydney, Australia 7Douglass Hanly Moir Pathology, Sydney, New South Wales, Australia 8Department of Microbiology and Infectious Diseases, Royal Women’s Hospital; Department of Microbiology, Royal Children’s Hospital and Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia 9Melbourne Sexual Health Centre, Carlton, Victoria, Australia.

Objective: Although High Resolution Anoscopy (HRA)-directed biopsy is regarded as the gold standard against which the accuracy of anal cytology is measured, both techniques can potentially miss anal HSIL (aHSIL). HPV 16 is the commonest causal agent of aHSIL. We therefore evaluated the separate and combined diagnostic accuracies of cytology and histology, based on a comparison with the prevalence of HPV16 and other high risk (HR)-HPV, and examined trends in HPV prevalence across combinations of cytology(c) and histology(h).

Methods: A community-based cohort of HIV infected and uninfected homosexual men aged 35 years and older underwent anal swabbing for cytology + HPV genotyping, and HRA-guided biopsy of lesions suspected of being HPV-related.

Results: Data were included on 605 of the 617 (98.4%) participants, each of whom who had an anal swab, HRA and HPV genotyping results available. The prevalence of cHSIL (17.9%) was lower than hHSIL (31.7%, p<0.001). The prevalence of composite-HSIL (i.e. HSIL detected by either method) was 37.7%. The prevalence of HPV16 in the swab declined from 50.0% in men with composite-HSIL to 31.1% in men with composite-atypical squamous cells suggestive of HSIL, to 18.5% in men with composite-low grade SIL, to 12.1% in men with composite-negative results (p-trend<0.001).

Conclusions: Significantly more HSIL was detected when a composite cytology-histology endpoint was used. Increasing grade of composite endpoint was associated with increasing HPV16 prevalence. These data suggest that a composite cytology-histology endpoint reflects meaningful disease categories and is likely to be an important biomarker in anal cancer prevention.

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Basic Science

Screening for Pre-Invasive and Invasive Glandular Lesions of the Cervix: Pap Test Results and Time to Diagnosis

Lea Moukarzel, MD1, Ana M Angarita, MD1, Anne F Rositch, PhD, MSPH2, Christopher VandenB, MD3, Reinou Groen, MD1, Amanda Ramos, MD1, Amanda Nickles Fader, MD1, and Kimberly L Levinson, MD, MPH1. Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, USA1; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA2; Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA3.

Objective: The objective of this study was to evaluate the result of the screening Pap test immediately prior to diagnosis and its association with the time to diagnosis of adenocarcinoma (AdCa) or adenocarcinoma in situ (AIS).

Methods: This is a retrospective cohort study of patients diagnosed with AdCa and AIS from 2005–2015 at a single large-volume institution. Pathologic data was combined with medical record abstraction to determine demographic and disease characteristics, Pap test immediately prior to diagnosis, and time from last screening to diagnosis. The average time from last pap to diagnosis of AdCa vs. AIS were compared using a student’s t-test.

Results: Of 117 cases (63 AdCa, 54 AIS) identified during the study period, 74% (37 AdCa, 50 AIS) had a record of the Pap test result preceding diagnosis. Median age was 39, 73% were Caucasion, and 16% were smokers. Women with AdCa were significantly older (mean 45 years) than those with AIS (mean 31years). The average time to diagnosis differed among women diagnosed with AdCa and AIS, with longer time to development of AdCa than to AIS. For both AdCa and AIS, the time to diagnosis decreased with increasing severity of cytology (Figure 1).

Conclusions: The time to diagnosis of AIS or AdCa is associated with the result of the Pap test immediately prior to diagnosis. Further investigation is needed to determine if additional screening tests, including HPV testing, can decrease the time to diagnosis of glandular lesions, particularly among women with low grade and normal Pap tests.

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Basic Science

The Study of Folate Receptor-Mediated Staining Solution (FRDTM) Testing Used in Cervical Cancer Screening

Yun Zhao, Mingzhu Li, Shuhui Cui, Chao Zhao, Lihui Wei. Department of Gynecology and Obstetrics, Peking University People’s Hospital, Beijing, China.

Objective: A multicenter clinic trail to evaluate the sensitivity and specificity of Folate Receptor-Mediated Staining Solution (FRDTM ) in detecting cervical intraepithelial neoplasia (CIN).

Methods: FRDTM is a special staining method for rapid visualization of CIN. The stain was recorded as positive or negative based on the color changes. HR-HPV tests and Pap liquid-based cytology were performed shortly before or concurrent with FRD testing. The colposcopy was performed for the patients with either ASC-US and above Pap test, or positive HPV testing or positive FRD.

Results: 1926 women with histological findings were included in the study. CIN2+ was found in 655 patients (34.0%) including 71 cervical cancers (3.7%). CIN1 and negative cases accounted for 27.1% and 38.9%, respectively. Pap results included NILM in 561women (29.7%), ASC-US in 543(28.7%), LSIL in 447 (23.6%), ASC-H in 109 (5.8%), AGC in 13 (0.7%), HSIL and above in 219 (11.6%). HPV positive rate was 88.9% (1643/1849). Positive FRD test was determined in 53.6% women (1032/1926). The sensitivity to detect CIN2+ lesions for abnormal Pap, positive HPV and positive FRD was 79.3%, 95.5%, and 77.9%, respectively. The specificity to detect CIN2+ lesions for abnormal Pap, positive HPV and positive FRD was 34.2%, 4.5%, and 58.9% respectively.

Conclusions: Compared with LBC and HPV test, FRD method has compatible sensitivity and high specificity to detect high grade cervical lesions. In addition, FRD is a very inexpensive and easy method, which can be used in less-developed counties or areas that lack the resources and trained personnel required for routine cervical screening.

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Cervical Cancer

AGC Subclasses and Risk of Invasive Cancers: A Prospective Case Series Study

Xuezhi Jiang 1,3, Emily J Amendola1, Andrew Boyd1, Peter F. Schnatz1-4. Reading Hospital, Department of Obstetrics and Gynecology1 and Internal Medicine2, Reading, PA Sidney Kimmel Medical College of Thomas Jefferson University, Department of Obstetrics and Gynecology3 and Internal Medicine4, Philadelphia, PA.

Objective: To assess the risk of invasive cancers associated with Atypical Glandular Cell (AGC) subclasses.

Methods: All cases of AGC were identified from a pathology database between 1/1/2005 – 01/1/2009. Demographics, cytology, histology findings, and final diagnosis of invasive cancers were recorded from the initial AGC diagnosis until 07/01/2015. A multivariate survival analysis was conducted using SAS v. 9.3.

Results: Of 230,780 Pap smears that were evaluated, a total of 444 patients (0.2%) were diagnosed with AGC. Of the 444, 429 patients had at least one follow up visit after AGC diagnosis. Mean (SD, Median, Min-Max) follow up time are 6.1 (2.7, 6.6, 0.1-10.4) years. Of the 429, 169(39.4%), 82(19.1%), 178(41.5%) were classified as AGC-endocervical origin (AGC-EC), AGC-not other specified (AGC-NOS), AGC-endometrial origin (AGC-EM), respectively. A total of 63 (14.7%) had at least one invasive cancer diagnosed after AGC, including 42 endometrial cancer, 10 breast cancer, 8 skin cancer, 2 cervical cancer, 2 thyroid cancer, 2 Hodgkin’s lymphoma, and 4 others. While analyzing Time-to-First invasive cancer, the survival curve of AGC-EC is clearly distinct from AGC-NOS and AGC-EM (log rank test, p=0.0009, Fig. 1). The risk of invasive cancer increases in a stepwise manner across AGC subclasses from AGC-EC, AGC-NOS, to AGC-EM (Cochran-Armitage trend test, p=0.001). Similar findings and stepwise trends were seen in the 272 women who had an endometrial biopsy done, while analyzing Time-to-Endometrial cancer (log rank test, p=0.024, Cochran-Armitage trend test, p=0.013).

Conclusions: The three AGC subclasses may carry different risk profiles for developing, and time to develop, post-AGC invasive cancers, including but not limited to endometrial cancer. There may be a stepwise increase in the risk of cancers across AGC subclasses from AGC-EC to AGC-NOS to AGC-EM.

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Cervical Cancer

Cervical Cytology Progression in Women Following Solid Organ Transplant

Margaret E Long 1, Paula D Chantigian1, and Amy L Weaver2. 1Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN; and 2Department of Statistics and Bioinformatics, Mayo Clinic, Rochester, MN.

Objective: Estimating the cumulative risk incidence of high grade cervical intraepithelial neoplasia cytology (HSIL) in women following solid organ transplant (SOT) will help guide recommendations for cervical cancer screening in this population.

Methods: After institutional review board approval, we identified women, ages 18–60 years, who received a kidney, liver, or pancreas transplant at a large academic center between January 1995 and December 2011. The study cohort consisted of HIV negative women with cervical cytology following the transplant. The cumulative incidence or risk of HSIL cytology following the first post-transplant cervical cytology was estimated using the Kaplan-Meier method.

Results: Of the 460 women who met the study criteria, mean age at transplant was 43.9 years. The first post-transplant cervical cytology was at a median of 1.2 years (IQR, 1.0-2.7), of which 419 (91.1%) were benign. 41 (8.9%) were ASCUS-HPV positive/favor dysplasia or higher for which immediate colposcopy is recommended.

Of the 419 with benign findings at the first post-transplant cytology, 316 had subsequent cytologic follow-up. Among these 316, the cumulative incidence of subsequent HSIL cytology was 1% (0–2.1%), 2% (0.4-3.6%) and 9.8% (5.7-13.8%) at 1, 2, and 5 years, respectively.

Women with HPV negative versus positive results had benign cytology 98.6% versus 33.3% (p<0.001).

Conclusions: Even with normal initial cytology after transplant, women with SOT have a five year risk of HSIL cytology of 9.8% The current recommendation for annual cytology for this group is not excessive.

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Cervical Cancer

Conservative Treatment of Adenocarcinoma In Situ: Post-Cone Surveillance and Time to Recurrence

Ana Angarita, MD1, Lea Moukarzel, MD1, Anne F Rositch, PhD, MSPH2, Christopher VandenB, MD3, Reinou Groen, MD, Amanda Ramos, MD, Amanda Nickles Fader, MD1, and Kimberly L Levinson, MD, MPH1. Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, USA1; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA2; and Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA3.

Objective: The natural history of AIS after conservative treatment with conization is not well understood. This study evaluates recurrence of dysplasia following conservative management of AIS and possible predictors of recurrence.

Methods: Retrospective cohort analysis of women treated with conization for AIS from 2005 to 2015 at a single large-volume institution. Recurrence was defined as abnormal cytology/biopsy, or positive human papillomavirus test. Fisher’s exact test was performed to evaluate the association of recurrence with clinico-pathologic features.

Results: Sixty-four women were diagnosed with AIS. The median age was 34 (18–61), 81.9% were Caucasian, and 12.7% were smokers. Of these 64 women, 32 (50%) underwent surveillance after conization. Among all 32 women, the median time to first post-treatment surveillance was 4.3 months (IQR: 2.3-6.3). A subsequent abnormal surveillance was observed in 19/32 women (59.4%) at a median of 8 months (IQR: 0.3-15.7) after conization. Abnormal screening results were ASCUS (11), LSIL (3), AGC (3), AIS (1), and endocervix curettage (ECC) with CIN1 (1). There was no association between the cytologic result and time to recurrence (p=0.06). ECC at first surveillance was performed in 10/19 women (52.6%); all were benign. Eight women with positive margins on initial cone recurred; four of these eight women were initially treated with a second cone.

Conclusions: More than half of women undergoing conservative treatment for AIS will develop abnormal cytology, and the majority within 8 months of treatment. Although no predictors of recurrence were identified in this small cohort, larger studies are needed to identify predictive features.

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Cervical Cancer

Effect of Structured Guidelines for Immediate LEEP After HSIL Pap on Patient Outcomes

Ali McGregor 1, Megan Guetzko2, Kimberly Gecsi3. Department of Obstetrics and Reproductive Biology, University Hospitals Case Medical Center, Cleveland, OH.

Objective: Determine the effect of immediate LEEP after HSIL pap on patient outcomes in an urban, Medicaid-based patient population.

Methods: Retrospective chart review of all patients seen in the resident clinic with HSIL pap results from June 2011 – June 2015, two years before and after the introduction of structured guidelines for immediate LEEP for HSIL in patients age 25 or older. Primary outcome was percentage of patients who received indicated excisional procedure. Secondary outcomes include percentage of patients lost to follow up and percentage of patients who underwent LEEP and did not have at least CIN2 on pathology result. Results were compared between groups using Chi-squared and Fisher’s exact tests. P value of 0.05 was considered significant.

Results: Of the 119 women that had HSIL pap during the time period, 40 never sought follow up. Of the women over 25 years of age who returned for care, 5/29 (0.172) women in the pre-intervention group did not get an indicated LEEP versus 1/16 (0.063) women in the post-intervention group (P=0.23). When comparing LEEP pathology results between groups, 9/24 (0.375) of the specimens were less than CIN 2 on pathology prior to our intervention versus only 2/15 (0.133) of the specimens after the intervention (P=0.08).

Conclusions: Performing an immediate LEEP does not increase the amount of unnecessary LEEPs performed and may decrease the number of patients that do not obtain an indicated procedure. This data supports ASCCP guidelines for immediate LEEP for HSIL pap in women over 25.

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Cervical Cancer

Evaluation of Risk-Based Colposcopy in the ALTS Trial

Angela H Liu 1, Mark Schiffman1, Julia C Gage1, Philip E Castle2, and Nicolas Wentzensen1. 1Division of Cancer Epidemiology and Genetics, National Cancer Institute; and 2 Department of Epidemiology and Population Health, Albert Einstein College of Medicine.

Objective: Women referred to colposcopy have a wide spectrum of underlying risk of precancer that could influence colposcopic practice and management. We sought to evaluate risk-strata based on HPV status, cytology, and colposcopic impression in women undergoing colposcopy.

Methods: Among participants in the ASCUS-LSIL Triage Study (including the immediate colposcopy and HPV triage arms), we stratified women based on enrollment HPV typing, study cytology, and colposcopic impression. In each group, absolute risk of CIN3+ at enrollment colposcopy and cumulative risk over 2-year follow-up were estimated.

Results: We observed substantial differences in risk of precancer across strata. Women with HSIL cytology, who were HPV16-positive, and high-grade colpscopic impression had a 71% baseline and 78% 2-year risk of CIN3+, respectively. HPV16-positive women with HSIL cytology and low-grade impression, and women with high-grade impression and either HSIL cytology or HPV16 infection, also showed significant CIN3+ risk exceeding the risk of HSIL. In contrast, women with normal colposcopy, <HSIL cytology, and absence of HPV16 infection had the lowest baseline CIN3+ risk (3.2%), below the colposcopy referral threshold in ALTS.

Conclusions: Risk assessment at colposcopy can inform colposcopy-biopsy practice and guide management. In the low-risk group, a normal colposcopy may confer higher reassurance that CIN3+ is not present; while in the highest risk groups, immediate treatment without biopsy confirmation could be considered according to current guidelines. Analyses evaluating the benefit of multiple biopsies in these strata are underway and will be presented at the meeting.

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Cervical Cancer

High-Grade CIN Detected by Colposcopic Directed or Random Biopsy Relative to Patient Age, Cytology, HPV 16, and Lesion Size

Ruifang Wu, MD1, 2, Qing Chen, MD1, Hui Du, MD1, 2, Robert G. Pretorius, MD3, Bin Yang, MD, PhD4, Xinfeng Qu, MD1, 2, Guixiang Wang, MD1,2, and Jerome L. Belinson, MD5,6. 1Peking University Shenzhen Hospital, Shenzhen, PR China; 2Shenzhen Key Laboratory on Technology for Early Diagnosis of Major Gynecological diseases, Shenzhen, PR China; 3Department of Obstetrics and Gynecology, Kaiser Fontana California, Fontana, California, USA; 4Department of Anatomic and Molecular Pathology, Cleveland Clinic, Cleveland, Ohio, USA; 5Women’s Health Institute, Cleveland Clinic, Cleveland, Ohio, USA; 6Preventive Oncology International, Inc., Cleveland Heights, Ohio, USA;

Objective: Determine whether p16 positive/CIN 2, CIN 3, and cancer (p16+CIN 2/CIN 3+) detected by colposcopic directed or random biopsy differ by age, referral cytology, HPV 16, and lesion size.

Methods: Data from the Shenzhen Cervical Cancer Screening Trial II where, at colposcopy, women who had directed and random cervical biopsies were reviewed to find women with CIN 2, CIN 3, or cancer; 227 such women identified had their paraffin embedded tissue blocks re-cut, reviewed, and then immune-stained for p16. Data was analyzed by Chi Square, Fisher Exact, and Linear regression.

Results: Following histopathologic review and p16 staining of CIN 2, 175 women were diagnosed with p16+CIN 2/CIN 3+. When compared to those diagnosed by colposcopic directed biopsy (n=138), those diagnosed by random biopsy (n=37) were more likely to have Cytology-Lo (cytology of Negative, ASC-US, or LSIL) (p=.07), less likely to have HPV 16 (p=.041), more likely to be ≥51 years of age (p=.022), and more likely to have 1 quadrant lesions (p<.001). Logistic regression analysis showed p16+CIN 2/CIN 3+ diagnosed by random biopsy was predicted by 1 quadrant lesions (p<.0001) and age ≥51 years (p=.03) but not by Cytology-Lo (p=.71) nor HPV 16 (p=.26).

Conclusions: Women with p16+CIN 2/CIN 3+ diagnosed by random biopsy are older and less likely to have HPV 16; hence CIN diagnosed by random biopsy may not be as virulent as CIN diagnosed by colposcopic directed biopsy. Regardless, we advise that CIN diagnosed by random biopsy be viewed like CIN diagnosed by colposcopic directed biopsy.

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Cervical Cancer

HPV/Cytology Cotesting at 3-year Intervals Results in Reduced Yield of Precancer per Screen Over Time

Michelle I. Silver 1, Mark Schiffman1, Barbara Fetterman2, Nancy Poitras2, Julia C. Gage1, Nicolas Wentzensen1, Thomas Lorey2, Philip E. Castle3, and Walter Kinney2. 1Clinical Genetics Branch, National Cancer Institute; 2Kaiser Permanente Northern California; 3Albert Einstein College of Medicine.

Objective: Cervical screening aims to detect and treat precancer to prevent cervical cancer mortality and morbidity, while minimizing overtreatment. HPV/cytology cotesting is now a preferred screening method, but the optimal interval is being questioned. Realistic longitudinal data are needed. We examined the population level effect on detection of precancer using Pap/HPV cotest performed at 3-year intervals since cotesting was introduced in 2003 at Kaiser Permanente Northern California (KPNC).

Methods: We calculated the annual rates of precancer detection for all women who received cervical cancer screening from age 30 onward at KPNC from 2003 to 2013, including >1.5 million screening visits. To estimate the cumulative impact of repeated screening at 3-year intervals, we also calculated precancer rates for a “closed cohort” that included only the subset of women who were first cotested in 2003-4.

Results: Rates of CIN2 and CIN3 detection remained steady in the total KPNC screening population as new women not previously cotested entered the population, bringing a continued influx of new disease to detect. In the stable, closed cohort, following only women who were enrolled in 2003-4 and continued to be cotested regularly, rates of CIN3 declined (2004-6 = 224/100,000; 2007-9 = 160/100,000; 2010-12 = 115/100,000), a decline not explained by age-adjustment.

Conclusions: Repeated cotesting at a 3-year interval drives down rates of precancer substantially, such that precancer rates are much lower in subsequent rounds than at the initial screen.

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Cervical Cancer

Impact of Guideline Changes on CDSS for Cervical Cancer Screening and Surveillance

Kathy L. MacLaughlin, MD1, Ravikumar Komandur Elayavilli, PhD1, Kavishwar B. Wagholikar, MD, PhD2, Marianne R. Scheitel1, Hongfang Liu, PhD1, and Rajeev Chaudhry, MBBS, MPH1. 1Mayo Clinic, Rochester, MN, USA 2Massachusetts General Hospital, Boston, USA.

Objective: Clinical decision support systems (CDSS) offer potential to improve guideline compliance and patient outcomes. We developed and previously assessed performance of a CDSS to automate standard cervical cancer screening guidelines based on electronic medical record data.1 Here we studied accuracy of CDSS after updates to include the latest revision of guidelines for screening and management of abnormal cervical cytology, HPV and colposcopic biopsy.

Methods: CDSS extracts data elements from structured and unstructured sources and provides care recommendations based on decision rules2 which are implemented in Drools rule engine3. CDSS system was run on 2453 patients. Stratified sampling done on 191 patients to cover all decision end-points. Clinician expert evaluated recommendations by reviewing medical record for each patient, comparing against ASCCP guidelines4; allowing identification of errors in CDSS. CDSS corrections were made and then CDSS was run on 3009 patients with random sampling of 395.

Results: CDSS-generated decision was correct in 161/191 initial cases (accuracy of 84%). We observed a 3% drop in accuracy compared to our earlier reported results1 which may be due to increased complexity of the updated ASCCP guidelines4. Accuracy improved to 94% after CDSS corrections.

Conclusions: Revision of practice guidelines resulted in increased complexity that impacted performance of CDSS. A systematic error analysis coupled with stratified sampling helped us understand micro behavior of CDSS and allowed us to improve accuracy. We will deploy the system in a big data environment and evaluate impact of clinical care recommendations for cervical cancer prevention at point of care.

Acknowledgement: Agency of Health Care Research and Quality (AHRQ R21HS022911) and National Library of Medicine, NIH (K99LM011575) supported this research.

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Cervical Cancer

Is Negative Co-Testing in HIV+ Women Associated with a Low Three-Year Risk of Cervical Pre-Cancers?

Elizabeth Stier, MD, Rachel Alade, MS, and Olivera Vragonic, MBA. Department of Obstetrics and Gynecology, Boston University School of Medicine, Boston, MA.

Objective: HIV+ women are more likely to have persistent cervical HPV infections, cervical neoplasia, and cervical cancer compared with HIV- women. Cervical cancer screening guidelines for HIV+ women include annual cytology. The role of HPV co-testing is undefined. We assessed whether HIV+ women, ≥30 years with normal cytology/negative HPV (-/-) co-testing could safely lengthen the screening interval to three years.

Methods: We conducted a retrospective chart review of HIV+ women aged ≥30 with normal cytology between 11/2008-12/2010 (index cytology) and at least 1 subsequent cytology at Boston Medical Center. Based on the HPV co-testing result associated with index cytology, we compared the incidence of subsequent histologic CIN-2+ through 12/2014.

Results: 48 of the 326 (14.7%) HIV+ women with normal index cytology tested HPV+. Subsequent diagnosis with CIN-2+ in HIV+/HPV+ women compared with HIV+/HPV- women was (4/48(8.33%) vs (9/278(3.24%) respectively (OR: 2.78 (95%CI: 0.80-9.21)). Mean interval for diagnosis of CIN2+ in HIV+/HPV+ women compared with HIV+/HPV- women was 338 days (121-538) vs. 1080 days (503-2036) respectively (p<0.025).

Conclusions: This clinical data supports findings from the US cohort of Women’s Interagency HIV study– HIV+ women undergoing cervical cancer screening with normal cytology and HPV- co-testing have a low risk of being diagnosed with CIN-2+ within the next 3 years. Thus, the cervical cancer screening interval for HIV+ women with -/- co-testing may be safely increased from 1 to 3 years. However, HIV+ women with normal cytology and +HPV testing should be followed more closely given the shorter interval to diagnosis of CIN-2+.

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Cervical Cancer

Office Hysteroscopy in the Diagnosis of Cervical Intra-Epithelial Neoplasia

Ahmad Sameer Sanad. Department of Obstetrics and Gynecology, Minia Maternity University Hospital, Minia University, Egypt.

Objective: To suggest and substantiate office hysteroscopy as a diagnostic tool for cervical glandular intraepithelial neoplasia in patients with cervical intraepithelial neoplasia.

Design: Prospective study

Setting: The early cancer detection unit (ECDU), Minia Maternity University Hospital, Minia University.

The study population was recruited from the attendees of the outpatient clinic of Minia Maternity University Hospital, in the periods of May 2013 and November 2014. The present study included 124 patients with an abnormal Pap smear results or positive results with visual inspection of the cervix with acetic acid.

Interventions: Hysteroscopic evaluation of the endocervical mucosa, performed with an office continuous-flow hysteroscopy after application of acetic acid 5% through operative channel. Patients with abnormal cervical findings underwent guided biopsies of the visualized abnormalities. Negative patients at hysteroscopic evaluation underwent blind endocervical curettage.

Main Outcome Measures. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of hysteroscopy plus guided biopsy.

Results: Cervical hysteroscopy diagnosed 9 cases of positive endocervical abnormalities. Guided biopsies agreed with hysteroscopy in 6 cases and 3 cases were negative. On the other hand, hysteroscopy failed to prove lesion present in blind endocervical curettage. The test performance showed a sensitivity of 86%, a specificity of 98 %, a PPV of 67 %, a NPV of 99% and diagnostic accuracy of 97.1%.

Conclusions: Hysteroscopy appears to be a reliable office technique, improving the detection of cervical intraepithelial lesions. The accurate localization of the lesions facilitates the depth of cone excision to be designed, thus leading to a more preservative treatment for the future fertility.

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Cervical Cancer

Population-Based Incidence Rates of Cervical Intraepithelial Neoplasia Post-HPV Vaccine Era in New Mexico, 2007-2013

Vicki Benard 1, Phil Castle2, Steve Jenison3, William Hunt4, Jane Kim5, Scott Norville6, Jacki Cuzick7, and Cosette Wheeler4. 1Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, Georgia 2Albert Einstein College of Medicine, New York, New York 3University of New Mexico, Department of Internal Medicine, Division of Infectious Disease 4House of Prevention Epidemiology (HOPE), University of New Mexico Health Sciences Center, Albuquerque, New Mexico 5Harvard T.H. Chan School of Public Health, Boston, Massachusetts 6Infectious Disease Prevention and Control Bureau, New Mexico Department of Health, Santa Fe, New Mexico 7Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, Charterhouse Square, London, UK.

Objective: Measuring the population impact of the human papillomavirus (HPV) vaccine adjusting for shifts in cervical cancer screening according to national guidelines is a critical need. The New Mexico Pap Registry (NMHPVPR), currently the only U.S. surveillance system that captures population-based estimates of both screening prevalence and cervical cancer precursors was used to compare rates using census- and screening-based denominators.

Methods: Incidence rates for cervical intraepithelial neoplasia grades 1, 2 and 3 (CIN1, CIN2, CIN3) were calculated by year and age group for women age 15 to 29 years with the denominator as the (1) total NM population from US Census and (2) total number of women with cervical cytology results. Annual percentage change was calculated to determine trends over time.

Results: From 2007 to 2013, 12,650 CIN1, 3867 CIN2, and 2445 CIN3 were diagnosed among women aged 15-29 years. The youngest age group (15-19 year olds) had the greatest CIN reductions; the case count decreased by year for all grades of CIN (CIN1: 598 to 36; CIN2: 145 to 5; CIN3 38 to 3). Incidence rates calculated based on the whole population significantly decreased annually for all age groups and grades of CIN; however when adjusting for screening only decreases in rates for the youngest age group were significant.

Conclusions: Even at this early stage, these data highlight issues related to measuring the impact of HPV vaccination in the context of changing practices in screening. NMHPVPR offers a unique opportunity to consider data driven risk-based modifications of screening strategies in partially vaccinated populations of young women.

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Cervical Cancer

Predictors of Recurrent or Persistent Disease After LEEP Procedure

Helen E. Cejtin, MD, Lindsay Zimmerman, MPH, Melissa Ann Matthew, MBBS, and Ashlesha Patel, MD, MPH. Northwestern University Feinberg School of Medicine.

Objective: Follow up recommendations after an excisional procedure vary depending on whether or not there is a positive ectocervical or endocervical margin or endocervical curettage (ECC). The purpose of this study is to evaluate the importance of these findings in predicting recurrent/persistent (r/p) disease in a sample of HIV seropositive and negative women.

Methods: LEEP procedures with a concurrent ECC performed at the Cook County ambulatory clinic between 9/29/08 and 4/15/14 were included in this study. Chart review was performed to collect demographic data, pathology results, and all subsequent cytology or histology. We examined the association of these factors with recurrent/persistent disease using chi-square and Fisher’s exact tests, and log-binomial regression.

Results: There were 242 women included for analysis. Of these, 9 LEEP specimens showed invasive cancer or adenocarcinoma in situ, and 15.7% were HIV-positive. Mean follow-up was 16.4 months. On bivariate analysis, HIV serostatus, LEEP histology, ectocervical margin, endocervical margin, and ECC were all associated with r/p disease. On multivariate regression, only HIV serostatus and ECC were associated with r/p disease. Among women with either a positive endocervical or ectocervical margin or ECC, the prevalence of r/p disease is 29% if they are HIV negative, and 75% if they are positive.

Conclusions: In our study, ECC seems more predictive of r/p disease than margin status. The majority of HIV positive women with positive margins or ECC have r/p disease, while most HIV negtive women do not. One should consider HIV-serostatus when deciding whether or not to perform repeat excision.

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Cervical Cancer

Risk-based action thresholds for cervical cancer screening and management in two large U.S. practice settings

Julia C. Gage 1, William C. Hunt WC2, Mark Schiffman1, Hormuzd A. Katki1, Li C. Cheung3, Orrin Myers4, Jack Cuzick5, Walter Kinney6, *Philip E. Castle7, *Cosette M. Wheeler8, and for The New Mexico HPV Pap Registry Steering Committee9. 1Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD; 2Department of Pathology. University of New Mexico Health Sciences Center, Albuquerque, NM; 3Information Management Services Inc., Calverton, MD; 4Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM; 5Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, Charterhouse Square, London, UK; 6Division of Gynecologic Oncology, Kaiser Permanente Medical Care Program, Oakland, CA; 7Albert Einstein College of Medicine, New York, NY; 8New Mexico HPV Pap Registry Steering Committee Members.

Objective: Current U.S. cervical screening guidelines based screening and management recommendations utilize comparative risks of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) after screening. Few cohorts are large enough to provide estimations for important risk-based management thresholds based on real-life clinical practice. Two of the largest U.S. clinical practice datasets are the New Mexico Human Papillomavirus (HPV) Pap Registry (NMHPVPR), a state-wide registry representing a diverse population with varied clinical practices, and Kaiser Permanente Northern California (KPNC), a large integrated health delivery system practicing routine co-testing since 2003.

Methods: A logistic-Weibull survival model was used to estimate and compare the cumulative 5-year CIN3+ risks among women age 21-64 screened in 2007-2011 in NMHPVPR and 2003-2013 in KPNC. Results were stratified by age and baseline screening results: negative cytology, atypical squamous lesion of undetermined significance (ASC-US) (with or without HPV triage), low-grade squamous intraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL).

Results: Among 453,618 women in NMHPVPR and 1,307,528 women at KPNC, the 5-year CIN3+ risk stratification by screening results was similar across populations: cytology negative=0.52% and 0.30% (p=<.0001), HPV-negative/ASC-US=0.72% and 0.49% (p=.5), ASC-US=3.43% and 3.39% (p=.8), HPV-positive/ASC-US=7.7% and 7.1% (p=.3), LSIL= 6.5% and 5.4% (p=.009), and HSIL=53.1% and 50.4% (p=.2). Age stratified analyses showed more variability, especially among women age <30, but patterns were comparable.

Conclusions: CIN3+ risks between NMHPVPR and KPNC were remarkably similar, suggesting that the absolute risks underlying risk-based management thresholds are possibly generalizable across US clinical populations and practice settings.

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Cervical Cancer

Sustainable Cervical Cancer Prevention Clinics Using the World Health Organization ‘See and Treat’ Methods: A Five Country Experience

Steven Morris 2, Jacquelyn Dang2, Jennifer Lang2, Patricia Gordon2, and Caroline Nitschmann 1,2. 1Division of Gyecologic Surgery, Department of Obstetrics and Gynecology, Rochester MN 2Cure Cervical Cancer, Beverly Hills, CA.

Objective: Cervical cancer is the leading cause of cancer deaths among women worldwide. CureCervicalCancer (CCC), a 501(c)(3) nonprofit organization, is dedicated to sustaining cervical cancer prevention clinics by utilizing local recourses and training native healthcare providers in the ‘See and Treat’ method as reported by the World Health Organization (WHO). We sought to describe our experience of five international clinics.

Methods: Patients screened and treated for precancerous cervical lesions at CCC clinics were retrospectively identified from March 2013 to August 2015. Clinic locations included Vietnam, Haiti, Kenya, Ethiopia, and Guatemala for a total of 46 clinics. Patients were screened by visual inspection with acetic acid (VIA). If patients screened positive they were offered treatment with cryotherapy. Local healthcare provider training was offered via intensive education presented in the native language in both visual and written forms in addition to hands on training. Continued education and support was provided in exchange for ongoing screening and creation of reliable patient registries.

Results: A total of 31,237 patients were screened. 3,630 (11.6%) patients were found to be VIA positive, of which 2,716 (8.7%) received cryotherapy treatment. Due to advanced disease, refusal, or equipment failure, 914 (2.9%) of these patients did not receive cryotherapy treatment. After local training, 223 healthcare providers were considered proficient in “See and Treat”. Data from prospective screening was collected and reported electronically on a monthly basis.

Conclusions: The unique CCC organizational model demonstrates that it is possible to maintain sustainable cervical cancer screening clinics through ongoing education and support.

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Cervical Cancer

The Effects of an Educational Intervention on Self-Sampling for Human Papillomavirus Acceptability: RCT

Eribeth Peñaranda, MD, Jennifer Molokwu, MD, MPH, Silvia Flores, MD, MS, PhD, Theresa Byrd, DrPH, and Navkiran Shokar, MD, MPH. Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, TX.

Objective: Compare the effectiveness of a high-intensity educational intervention with a low-intensity intervention on US-Mexico women’s attitudes towards self-sampling.

Methods: Design: RCT. Setting: Low-income communities in El Paso, Texas. Participants: Women 30-65 years who had not had cervical cytology in > 3 years. Intervention: Women were randomized to either in-person education by a community outreach worker (high-intensity) about HPV, self-sampling, and self-collection or written instructions only (low-intensity) education. All women performed self-sampling using an FDA-approved device. Outcomes: self-sampling acceptability scores, HPV and cervical cancer knowledge, perceived susceptibility and perceived severity of HPV infection and intention to use self-sampling.

Results: 201 women were enrolled, (100 high-intensity and 101 low-intensity), mean age was 46 years (SD 8.3). Intervention had no effect on self-sampling acceptability scores, or testing preference: Pap vs. self-sampling; but it did increase HPV knowledge scores which was 0.729 (95% CI 0.377 to 1.081, p <.001) higher in high intervention group compared to low intervention group after adjusted for significant confounders. Self-sampling was regarded as less painful and less embarrassing than pap by all participants (p<0.05). The majority of women reported that they would recommend self-sampling to others (97.5%), would use it if it were available over-the-counter (90.7%) and would use it if doctor recommends it (97.0%).

Conclusions: Intense education about self-sampling for HPV infection promotes an increase in knowledge about HPV and cervical cancer. Underscreened/unscreened women reported high intention to use self-sampling if it becomes available.

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Emancipatory Praxis for Cervical Cancer Health Equity in Guatemala

Susan D. Driscoll1, and Rhonda L. Goodman1. 1Florida Atlantic University, Christine E. Lynn College of Nursing, Boca Raton, FL.

Objective: Cervical cancer is the leading cancer diagnosis and cause of cancer death among women in Guatemala and other low resource countries.Women’s inability or reluctance to access cervical cancer screening (CCS) contributes to cervical cancer morbidity and mortality. TheWHO (2010) estimated that only 50% of Guatemalan women had pelvic exams and 35% had effective CCS coverage, despite its efficacy and availability. Fatalism, mistrust of healthcare providers, masculine/feminine beliefs, limited knowledge, and community/social support are reported barriers and facilitators to CCS in high incidence populations. However, no research on beliefs and attitudes toward CCS in Guatemala has been reported. This study explored women’s beliefs and attitudes affecting their ability to access CCS inGuatemala to guide practice and reduce disease burden among thesewomen.

Methods: Data was gathered over six weeks of observation and two weeks of active participation. Informal and semi-structured interviews with women who helped organize community CCS clinics were conducted. Field notes and interview transcriptions were analyzed for themes.

Results: Five barriers and facilitators were revealed: fear/shame, “machismo”, education/experience, cost, and self efficacy. Results suggest that sustainable CCS through community collaboration and education for women and men may empower participation in CCS.

Conclusions: Emancipatory praxis within Guatemala’s more peaceful postwar recovery is needed to deliver sustainableCCS grounded in cultural humility. Building knowledge and trust between providers and community could create a forum for culture care, lessening oppression, empowering women, and reducing cervical cancer health disparities and disease burden among Maya women.

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Agreement Between Endocervical Brush and Endocervical Curettage in Patients Undergoing Repeat Endocervical Sampling

David W. Doo 1,2, Meredith J. Alston1,2, Sara E. Mazzoni2, and Elaine H. Stickrath2. 1Department of Obstetrics and Gynecology, University of Colorado, Aurora, CO 2Department of Obstetrics and Gynecology, Denver Heath Medical Center, Denver, CO.

Objective: Evaluate agreement between an abnormal endocervical brush (ECB) collected at the time of colposcopy and subsequent endocervical curettage (ECC).

Methods: All women evaluated for lower genital tract disease at a single academic institution were prospectively entered into a database. The database was queried for all women who had a colposcopic exam with ECB between April 2013 and June 2015 and subsequently returned for an ECC to further evaluate eligibility for expectant management or ablative therapy. ECB and ECC results were divided into two groups: “low-grade” included low-grade squamous intraepithelial lesions (LSIL) or atypical squamous cells of undetermined significance (ASCUS); “high-grade” included high-grade squamous intraepithelial lesions (HSIL) or atypical squamous cells-cannot exclude high-grade (ASC-H). Women with atypical glandular cells and unsatisfactory ECB results were excluded. Percent agreement between ECB and ECC were calculated based on these categories.

Results: Seventy-nine women were included: 54 (68%) had a low-grade ECB and 25 (32%) had a high-grade ECB. Of those who had a low-grade ECB, 4 had an LSIL ECC, 3 had an HSIL ECC and 46 were negative, resulting in an agreement of 7.4% (4/54). Of those who had a high-grade ECB, 1 had an LSIL ECC, 4 had an HSIL ECC and 20 were negative, resulting in 16% (4/25) agreement.

Conclusions: Our data suggest that ECB collected at the time of colposcopy over-estimates the presence of endocervical disease, and therefore ECC may be a better choice for endocervical sampling in those women otherwise eligible for expectant management or ablative therapy.

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Are Women with Abnormal Pap Smears Being Discharged from Colposcopy too soon?

Anna Kone1,2, Li Wang1, Julia Gao1, and Rachel Kupets 1,3. 1Cancer Care Ontario, Toronto, ON, Canada, 2University of Toronto, Toronto, ON, Canada, 3Sunnybrook Cancer Center/University of Toronto, Toronto, ON, Canada.

Objective: This study aims to determine the subsequent cervical cancer (CCA) risk of women discharged from colposcopic units without treatment after index abnormal cytology as compared to those who are treated.

Methods: A retrospective cohort study identified women who had a first time cytologic abnormality between 2007 and 2010 and underwent colposcopy within one year. The end of the colposcopic episode was defined as no colposcopic activity for 14 months. Treatment status was determined within the episode of care. The cohort was followed up to March 2015 and incidence of CCA post colposcopy was determined. Logistic regression assessed impact of colposcopic care, screening and patient factors on subsequent cervical cancer risk.

Results: 62% and 28.5% of HG (n=14,787) and LG (n=41,916) had treatment. 28% and 37% of women with HG and LG abnormalities had only one colposcopic evaluation. Subsequent cancer incidence in the untreated HG group was 1.1% vs. 0.3% in the treated HG group. For the LG group, cancer rates were 0.08% in both treatment groups. In the multivariate analysis in HG group, adjusted impact of treatment was reduced and no longer statistically significant OR=1.2 (95% CI 0.6-2.4). Other factors associated with CCA in the HG group were advancing age as compared to 21–29 years old, no screening post colposcopy (OR 2.0; 95% CI 1.2- 3.3) and duration of colposcopic episode 0 month (one evaluation only) vs >= 2 years (OR 8.7; 95% CI 2.8- 26.7). The effect of colposcopy duration was also significant in LG (OR 5.1; 95% CI 1.3- 20.8).

Conclusions: Women who are untreated, with index high grade cytology remain at elevated risk for cervical cancer when the colposcopic episode is limited to one exam. Centralized programs are required to ensure that such women are not discharged prematurely or lost to follow up from colposcopy and subsequent screening.

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Evaluation of the Practice Patterns of Practitioners Performing Cervical Biopsies

Kristen Mosier, M.D.1, and Michael Gold, M.D.2. 1Department of Obstetrics and Gynecology, University of Oklahoma School of Community Medicine, Tulsa, OK.; and 2Department of Obstetrics and Gynecology - Gynecology Oncology, University of Oklahoma School of Community Medicine, Tulsa, OK.

Objective: Studies demonstrate improved sensitivity for cervical HSIL detection when multiple colposcopic biopsies are performed. Little data exists regarding current practice patterns of practitioners performing cervical biopsy procedures (CBP). Additionally, biopsies may be sent individually or combined as a single specimen. The objective of this study is to evaluate the practice patterns of practitioners performing CBP regarding both number and collection method.

Methods: A retrospective computer database review was performed on cervical biopsy specimens processed by Regional Medical Laboratory between 01/01/2012 - 06/30/2015. All data is de-identified. The number of specimens per case, including the incidence of ECC, was evaluated by provider and preceding cytology.

Results: 8,225 CBP were performed among 299 providers, including 30.2% for ASCUS, 42.4% for LSIL, 8.6% for HSIL+. Mean and median numbers of CBP performed per provider was 27.5 (range 1-487) and 6, respectively. Overall, 35.9% included 1 biopsy, 18.1% 2, 6.8% 3, and 48.3% 4+. Multiple biopsies were significantly more common among patients with HSIL (79%) than ASCUS (60%) (p < 0.01). It appears that 51.7% of the time multiple specimens were sent within 1 container. More specimens were batched with HSIL (62.1%) than ASCUS (49.4%) (p < 0.01). Overall, 68.8% of procedures included an ECC, with more performed with ASCUS (70.8%) than HSIL (65.5%) (p < 0.05).

Conclusions: Most providers performing CBP do so rarely (<2 per year), but most included multiple biopsies and an ECC. Further evaluation needs to be performed to determine the varying effectiveness of these practices.

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p16 Expression in Colposcopically-Directed and Random Cervical Biopsies of CIN2 and CIN3

Cynthia Arvizo, MD1**, Qing Chen, MD2**, Hui Du, MD2, Bin Yang, MD, PhD3, Robert G. Pretorius, MD4, Ruifang Wu, MD2, and Jerome L. Belinson, MD1,5. 1Women’s Health Institute, Cleveland Clinic, Cleveland, OH, USA; 2Department of OB/GYN, Peking University Shenzhen Hospital, Shenzhen, China and the Key Laboratory on Technology for Early Diagnosis of Major Gynecological diseases, Shenzhen, PR China; 3Department of Anatomic and Molecular Pathology, Cleveland Clinic, Cleveland, OH, USA; 4Department of Obstetrics and Gynecology, Kaiser Fontana California, Fontana, CA, USA; 5Preventive Oncology International, Inc., Cleveland Heights, OH, USA **Contributed equally to this work.

Objective: The significance of small, thin, colposcopically undetectable CIN2/3 lesions has been questioned, so we investigated if colposcopically-directed biopsies and random (colposcopically-undetectable) biopsies of CIN 2/3 express p16 similarly.

Methods: Patients diagnosed with CIN2 and CIN3 by exocervical biopsy were identified from the SHENCCAST II (Shenzhen Cervical Cancer Screening Study II) database, a large population-based clinical trial in Guangdong Province in China. Blocks from each cervical quadrant with CIN2 and CIN3 were recut, reviewed, and immunostained for p16. Diffuse staining was considered p16 positive, whereas focal or no staining was considered p16 negative. The pathologist was blinded to initial colposcopic impression.

Results: There were 232 exocervical biopsies from 125 patients showing CIN 3 (76 biopsies with CIN2). The proportion of random cervical biopsies showing CIN 3 that were p16 positive (91.7%, 55/60) was similar to that of colposcopically-directed biopsies (97.7%, 168/172, p=.052, Fisher Exact). The proportion of random cervical biopsies showing CIN2 that were p16 positive (82.8%, 19/23) was similar to that of colposcopically-directed biopsies (86.8%, 46/53 directed p=.73).

Conclusions: Random biopsies of both CIN2 and CIN3 demonstrate similar p16 expression as colposcopically visible lesions, and are therefore expected to behave similarly. We continue to advocate the POI (Preventive Oncology International) micro-biopsy protocol for colposcopy that includes both directed and random biopsies.

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HPV Diseases

Detection of HPV Infection in Oropharyngeal and Oral Cavity Cancers

Elizabeth A. Kostas-Polston, PhD, APRN, WHNP-BC, FAANP, FAAN(1,2), Joy N. Miedema, MPH(1). Daniel K. Inouye Graduate School of Nursing; Uniformed Services University of Health Sciences; Bethesda, MD(1), Robert Wood Johnson Foundation Nurse Faculty Scholar.(2)

Objective: The study was conducted to compare the performance (i.e. sensitivity, specificity) of molecular assay and cytological evaluations to identify HPV infection using tissue, exfoliated cells and saliva collected from the oropharynx and oral cavity.

Methods: Using a cross-sectional design, this exploratory pilot study included 41 individuals with a lesion in their mouth or on their tonsils recruited from the Saint Louis University Head & Neck Cancer Clinic. Participants provided exfoliated cells from the lesion, saliva samples, and tissue (routine biopsy). Analytic methods and biological samples were tested in various combinations and compared to the gold standard (biopsy tissue/p16 IHC Staining) (refer to Table 1). The sensitivity and specificity, with 95% confidence intervals (Clopper-Pearson), for all of the combinations were calculated.

Results: The sensitivities for the Oragene-Saliva-CervistaHR, ThinPrep-Saliva-CervistaHR, ThinPrep-Scraping-CervistaHR, and ThinPrep-Scraping-Cytology were 100%, 50%, 73.68%, and 36.84%, and specificities were 23.81%, 66.67%, 80.95%, and 71.43%, respectively. There were no statistically significant differences between their performance when testing oropharyngeal and oral cavity lesions (p > 0.05).

Conclusions: Of the four combinations tested, we recommend further investigation of the ThinPrep-Scraping-CervistaHR test. If proven to be effective, this mildly invasive, readily available, and cost effective method can promote early detection and improve prognosis for the new generation of OPSCC patients.

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HPV Diseases

The Proportion of CIN3 and Cancer Caused by HPV16/18 and Other High Risk Genotypes Might Vary by Race/Ethnicity

Julia C. Gage 1, Mark Schiffman1, Tina Raine-Bennett2, Orestis A. Panagiotou1, Barbara Fetterman3, Joan L. Walker4, Rosemary E. Zuna5, Michael A. Gold6, Terence Dunn5, Brian Befano7, Nancy E. Poitras3, Thomas Lorey3, Philip E. Castle8, and Nicolas Wentzensen1. 1Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD, USA; 2Division of Research, Kaiser Permanente Northern California, Berkeley, CA, USA; 3Regional Laboratory, Kaiser Permanente Northern California, Berkeley, CA, USA; 4Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA; 5Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA; 6Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, Tennessee, USA; 7Information Management Services Inc., Calverton, MD, USA; 8Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.

Objective: Cervical cancer prevention programs prevent or detect HPV infection using vaccines and screening tests that target different oncogenic genotypes. Their effectiveness may vary if genotypes are not equally prevalent across populations. Some studies suggest genotype attribution in precancers, and possibly cancers, might vary by race/ethnicity. We examined this question in 4 US studies.

Methods: Within PaP, ALTS, and SUCCEED studies the fraction of cases caused by different types was estimated using HPV genotyping from exfoliative specimens. HPV genotypes detected in cervical cancer specimens from The Cancer Genome Atlas (TCGA) were included. By study and within disease category, the prevalence of HPV genotypes was compared by race/ethnicity using the prevalence difference. HPV genotypes were grouped according to oncogenic genotypes in current HPV vaccines: HPV16/18 and HPV16/18/31/33/45/52/58. Study-specific prevalence differences (PD) were combined through random-effects meta-analysis.

Results: Compared to Non-Hispanic (NH)-Whites [n=396], the prevalence of HPV16/18 among cancers was lower in Blacks, but not statistically significant [n=35; PD=−16%,p=.1] and similar in Hispanics [n=85;PD=+7%,p=.4], Asians [n=53; PD=+2%,p=.8]. Compared to NH-Whites [n=2,033], the prevalence of HPV16/18 among CIN3 cases was lower in Blacks [n=317; PD=−13%,p<.001] and Asians [n=495; PD=−11%,p<.001] and similar in Hispanics [n=576; PD=−2%,p=.6]. The prevalence of HPV16/18/31/33/45/52/58 was similar among both cancer and CIN3 cases (for all comparisons with NH-Whites: PD<=4%,p>.2). Findings were similar after age-adjustment.

Conclusions: In cancer and CIN3 cases, Blacks had less HPV16/18 (particularly HPV16) but a similar proportion of HPV16/18/31/33/45/52/58 compared to NH-Whites. Analysis of cancers was limited by smaller numbers but consistent with accumulated international data.

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HPV Diseases

The Risk Factors of Progression for HPV 16 Infected Women with ASC-US or LSIL

Kyeong A So, Ki-Heon Lee, In-Ho Lee, Mi Kyung Kim, Yoo Kyung Lee, and Tae-Jin Kim. Department of Obstetrics and Gynecology, Cheil General Hospital & Women’s Healthcare Center, College of Medicine, Dankook University, Seoul, Korea;

Objective: To evaluate the risk factors of progression for atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL) in HPV 16 infected women.

Methods: We analyzed the data showing HPV 16 infection from the Korean HPV cohort study. The Korean HPV recruited women aged 20 to 60 with abnormal cervical cytology (ASC-US or LSIL) between April 2010 and October 2014 from five institutions nationwide. Women of the cohort were followed up every six month interval with cervical cytology and HPV DNA testing.

Results: Among enrolled 1,158 women, one hundred forty-three women showed HPV 16 positivity (85 of single infection and 58 of multiple infection) at enrollment. Among HPV 16 positive women at 6 months follow-up, cervical cytology showed progression in 27.0%, unchange in 23.0%, and regression in 50.0%. HPV 16 infected women showed higher progression rate than other types of HPV infected women (relative risk [RR], 1.75; 95% confidence interval [CI], 1.08-2.84, P=0.028). Persistent HPV 16 infections for 6 and 12 months were found more progression rate than incidental infection or clearance group, relatively (P<0.0001). Logistic regression analysis showed a significant relationship between cigarette smoking and cytological progression (RR, 4.15; 95% CI, 1.01-17.00).

Conclusions: HPV 16 positive women with ASC-US/LSIL showed higher progression rate of the cervical cytology. In addition cigarette smoking may play role a risk factor of cytological progression.

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HPV Screening and Management

The Development and Evaluation of a New Solid Media Specimen Transport Card for Population Based Cervical Cancer Prevention

Kathryn Maurer 1, Hongxue Luo2, Zhiyong Shen3, Guixiang Wang2,4, Hui Du2,4, Chun Wang2,4, Xiaobo Liu1, Zhihong Liu2, Lijie Zhang2, Yanqiu Zou2, Xinfeng Qu6, Ruifang Wu2,4, and Jerome Belinson1,6. 1Gynecologic Oncology Division, Women’s Health Institute, Cleveland Clinic, Cleveland, OH, USA; 2Department of Ob/Gyn, Peking University Shenzhen Hospital, Shenzhen, PR China; 3Hyde Biomedical Corporation, Wuhu City, Anhui, PR China; 4Shenzhen Key Laboratory on Technology for Early Diagnosis of Major Gynecological diseases, Shenzhen, PR China; 5Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA, e Preventive Oncology International, Cleveland Heights, OH, USA; 6Preventive Oncology International, Inc., Cleveland Heights, Ohio, USA.

Objective: To develop and evaluate a low-cost solid media transport card for use in high-risk human papillomavirus detection (HR-HPV).

Methods: The Preventative Oncology International (POI) card was constructed using PK 226 paper® treated with cell-lysing solution and indicating dye. Randomized vaginal samples from women referred for colposcopy were applied to the POI card and the indicating FTA (iFTA) elute card. A cervical sample was placed in liquid media prior to colposcopy. All specimens were tested for HR-HPV with a PCR-based HPV genotyping assay. Color change was assessed at sample application and in the laboratory. Color stability of the POI card and iFTA elute card was tested at 75% and 90% humidity.

Results: 319 women were enrolled. Twelve women had at least one insufficient sample with no difference between media (p=0.36). 91.2% of POI and 99.9% of iFTA elute cards changed color (p<0.001). When compared to liquid samples, there was good agreement for HR-HPV detection with kappa of 0.81 (95% CI 0.74-0.88) and 0.71 (95% CI 0.62-0.79), POI and iFTA respectively. Sensitivity for ≥CIN2 was 100% (CI 100-100%), 95.1% (CI 92.7-97.6%), and 93.5% (CI 90.7-96.3%) for the HR-HPV PCR-based for the direct sample (SurePath), POI card, and iFTA card respectively. There was no color change in the POI card noted at 75% or 90% humidity; but the iFTA changed within 24 hours at 90% humidity.

Conclusions: The POI card is suitable for DNA transport and HR-HPV testing. This low-cost card has the potential to make cervical cancer screening programs more affordable worldwide.

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HPV Vaccination

Impact of a Prior History of HPV Vaccination on the Prevalence of HPV and Cytological Abnormalities in Women 21–35 Years

Thomas C Wright, Jr1, Valentin Parvu2, Charles Cooper2, Karen Yanson2, and Salma Kodsi2. 1Department of Pathology and Cell Biology, Columbia University, New York, NY, 2BD Diagnostics, Sparks, MD.

Objective: The HPV vaccine was FDA-approved in June 2006. Routine vaccination is recommended for girls 11-12 years and "catch-up" vaccination through age 26 years. Few studies have assessed vaccine impact on the prevalence of HPV genotypes and cytological abnormalities in women 21-35 years in the U.S.

Methods: The BD HPV Onclarity study is an ongoing U.S. study involving 31 collection sites in 18 states. 33,858 women 21-83 years were enrolled between August 2013–June 2015. At enrollment, women had a gynecologic examination including a SurePath cytology specimen that was tested for high-risk HPV genotypes using the BD HPV Onclarity assay that provides genotyping information for HPV 16, 18, 31, 33/58, 35/39/68, 45, 51, 52, 56/59/66. We compared the prevalence of HPV genotypes and cytological abnormalities in women 21-35 years stratified by self-reported HPV vaccination history.

Results: The Table shows significant differences between unvaccinated (UV) and vaccinated (V) women.

Minor differences were observed in the prevalence of other HPV genotypes.

Conclusions: A prior history of HPV vaccination is associated with significant reductions in the prevalence of HPV 16, 18, 31 and ASCUS-HPV(+)/LSIL+ and HSIL+ in women 21-34 years of age.



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HPV Vaccination

Impact of Number of HPV Vaccine Doses on Genital Warts Diagnoses Among Urban US Adolescents

Rebecca Perkins (1), Aaron Legler(2), and Amresh Hanchate(2). (1) Department of Obstetrics and Gynecology, Boston University School of Medicine/Boston Medical Center (2) Department of General Internal Medicine, Boston University School of Medicine/ Boston Medical Center.

Objective: WHO guidelines allow a two-dose schedule for HPV vaccination based on immunogenicity studies, but effectiveness data are limited.

Methods: We conducted a retrospective cohort study of females aged 15-26 years old, with no prior history of genital warts, receiving care at 7 health centers between 2007-2014. Patients were assigned an HPV vaccination state of 0, 1, 2, or 3 doses based on the last dose recorded in the medical record with ≥6 months of follow-up after that dose. Subjects were followed until they were diagnosed with genital warts or reached age 27. Multivariable Poisson regression was performed to determine the risk of genital warts associated with vaccine dose and age at vaccination.

Results: We examined 8924 subjects. Mean age was 18, 59% were Black, 10% White, and 10% Hispanic. 27% of subjects received 0 doses, 7% received 1 dose, 9% received 2 doses, and 58% received 3 doses. 2.3% were diagnosed with genital warts during the study period (mean exposure 34 months). Receiving 0, 1 or 2 doses was associated with twice the risk of developing genital warts compared with receiving 3 doses (P<0.01). Completing 2 or 3 doses prior to age 14 did not improve effectiveness. Median time between receipt of doses 1 and 2 was 154 days.

Conclusions: Completion of 3 doses of HPV vaccine appears necessary for maximum protection. Prospective effectiveness studies of two-dose schedules are necessary prior to enacting policy changes.

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HPV Vaccination

Racial/Ethnic Differences in the Prevalence of Prior HPV Vaccination in Females 18 years of Age in Two Large Integrated Health Care Systems in California

Chun Chao1, Tracy Becerra1, Michael Silverberg2, Virginia Quinn1, Douglas Corley2, Christopher Jensen2, Qiaoling Chen1, Natalia Udaltsova2, Angela Li1, and Neal Lonky 3. 1Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA, 2Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA, 3Department of Obstetrics and Gynecology, Orange County Medical Center, Kaiser Permanente Southern California, Anaheim, USA.

Objective: The human papillomavirus (HPV) vaccine has the potential to substantially reduce the clinical and economic burden of cervical cancer. National surveys indicate variations in HPV vaccine uptake by race/ethnicity. Yet, it is unclear if the variations were due to differential healthcare coverage/access. Here, we determined the prevalence of HPV vaccination by race/ethnicity in young female members of Kaiser Permanente (KP) Southern & Northern California who have relatively equal healthcare coverage including free HPV vaccination.

Methods: Females who reached age 18 in 2010-2013 and had continuous KP membership since the approval of Gardasil (June 2006) were included. Information on age, race/ethnicity and vaccination history (0, 1, 2, 3+ doses) was collected from KP’s electronic medical records. Differences in vaccination history by race/ethnicity were tested using chi-square tests.

Results: The study population included 110,166 eligible women: 34% white, non-Hispanic, 12% black, 35% Hispanic, 11% Asian, and 8% other/unknown. Prevalence of HPV vaccination was 74% overall; 72% in whites, 70% in blacks, 80% in Hispanics, and 76% in Asians (p<0.01). Prevalence of three-dose completion was 52% overall; 52% in whites, 44% in blacks, 57% in Hispanics, and 55% in Asians (p<0.01).

Conclusions: Despite having continuous access to health care and free HPV vaccines, there were racial/ethnic differences in HPV vaccine uptake and completion. Hispanics had the highest uptake, and blacks had the lowest proportion completing three doses. These results suggest the need for interventions to increase vaccine uptake and completion, especially among certain racial/ethnic subgroups such as blacks.

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Inhalant Allergy in Chronic Vaginitis; Diagnoses, Sensitivities, Co-Morbidities and Response to Sublingual Immunotherapy

Demetrios S. Theodoropoulos 1, Colleen K. Stockdale2, Daniel R. Duquette3, and Mary S. Morris1. 1Allergy Associates of La Crosse, Onalaska, WI; 2University of Iowa Hospitals and Clinics, Department of Obstetrics & Gynecology, Iowa City, IA; and 3Department of Health Education and Health Promotion, College of Science and Health, University of Wisconsin, La Crosse, WI.

Objective: Atopy is present in 25-54% of patients with Chronic Vaginitis Syndrome (ChVS). The objective of this study is the characterization of sensitization patterns and diagnoses, and the evaluation of inhalant allergen immunotherapy used in ChVS.

Methods: Methods: Fifty two patients referred for allergy evaluation over a 44 month period were studied. Charts were reviewed and patients contacted to establish: i) gynecological diagnoses, ii) allergic-immunological diagnoses, iii) IgE-mediated sensitivity to airborne allergens, and iv) response to sublingual immunotherapy.

Results: Recurrent vulvovaginal candidiasis was identified in 34 (65%); vestibulodynia in 12 (23%); and contact dermatitis in 10 (19%) patients. Co-morbidities included: non-reflux gastrointestinal complaints in 11 (21%), gastroesophageal reflux in 5 (9%), migraines in 9 (17%), chronic non-migrainous headaches in 8 (17%), and chronic sinusitis in 6 patients (11%). Asthma was diagnosed in 8 patients (15%). Oral allergy syndrome was present in 6 (11%).

Most frequent sensitivities were to: ragweed in 33 (63%), molds in 26 (50%), dust mites in 23 (44%), and grass in 12 (23%) patients. Mono-sensitization was demonstrated for ragweed in 7 (13%), and for molds, dust mites and grass for 3 (5%) patients each. Candida sensitization was present in only 15 patients (28%). Response to immunotherapy was generally favorable with pruritus/irritation being more responsive than visceral pain.

Conclusions: In a Midwestern referral population, ChVS compounded by inhalant allergy showed: i) high incidence of recurrent vulvo-vaginal candidiasis without commensurate rates of Candida IgE-mediated sensitization, ii) frequent co-morbid conditions, and iii) sensitization to allergens typical for the Midwest.

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