A Cocktail of HPV-L1 and PD-L1 Proteins as Biomarkers for Improved Detection of CIN2+ after HPV Primary Screening
Zeng Xi1 and Xi Ming-Rong1. 1Sichuan University
Objective: To analyze the clinical performance of PD-L1 and HPV-L1 proteins dual-stained cytology and pathology triaging the high-risk human papillomavirus (hr-HPV) positive participants in Chinese women.
Methods: 1988 women (age range 20–64) attending HPV based primary screening were enrolled into a regional prospective study in 2017. A total of 307 HPV positive women were tested for liquid-based cytology (LBC) and biomarkers on residual ThinPrep material. All tests were performed on the same sample. Women infected with HPV 16/18 type or 12 other hr-HPV types with abnormal cytology (atypical squamous cells of unknown significance or worse) were referred to colposcopy and biopsy. We evaluated the accuracy of HPV-L1 and PD-L1 among all HPV-positive women for detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) during preliminary follow-up compared with cytology and HPV genotyping. All statistical tests were two-sided.
Results: The positivity of HPV-L1 decreased with histology severity, from 79.3% in normal, 58.7% in CIN1, 31.2% in CIN2, 7.4% in CIN3 to 4.9% in cervical cancer. And PD-L1 increased from 13.1% in normal, 25.3% in CIN1, 45.7% in CIN2, 68% in CIN3 to 100% in cervical cancer. The two markers’ expressions were significantly difference in HPV16/18 group (OR: 9.73 (95% CI: 7.62-18.82)) and other 12 hr-HPV types group (OR: 6.65(95% CI: 5.8-9.9)) compared with hr-HPV negative group. The sensitivity and specificity of HPV-L1 and PD-L1 to detect CIN2+ in HPV-positive women were 89.82% and 73.91% respectively.
Conclusions: HPV-L1 and PD-L1 dual staining provided a significantly higher sensitivity and non-inferior specificity. These two biomarkers might be considered as efficient triaging tools to perfect HPV primary screening, especially in settings where experienced cytopathologist is not available and probably allow longer intervals in HPV-positive, triage-negative women.
Cervical Cancer Screening in Transgender Men in El Salvador: A Pilot Study
Mauricio Maza1, Mario Melendez1, Alejandra Herrera1, Xavier Hernandez2, Bryan Rodriguez2, Montserrat Soler1, Karla Alfaro1, Rachel Masch1, and Miriam Cremer3. 1Basic Health International, 2Organización Generación Hombres Trans El Salvador, 3Cleveland Clinic
Objective: There is limited information on cervical cancer screening in transgender men in low and middle-income countries (LMIC). It has been reported that the use of the Pap smear in this underserved population provides a greater number of unsatisfactory Pap smear results than in non-transgender persons. The purpose of this pilot study is to assess the feasibility of cervical cancer screening among members of this group using a self-sampling HPV test.
Methods: Participants were transgender men of the Organización Generación Hombres Trans El Salvador (Trans Men Generation Organization of El Salvador) between the ages of 19 and 55. After providing informed consent, 24 participants were administered a questionnaire pertaining to sociodemographic information, lifestyle and sexual behaviors, and knowledge about cervical cancer prevention. Screening was performed with a vaginal self-sample careHPV test. Participants who had a positive HPV result were offered a colposcopy evaluation.
Results: Almost all participants (23 out of 24) agreed to conduct vaginal self-sampling with a careHPV brush. Of these, 3 out of 23 (13%) tested positive and the rest were negative. Colposcopies and biopsies were accepted by all 3. One was diagnosed with CIN3, while 2 were diagnosed with CIN 1.
Conclusions: The use of HPV self-sampling tests in transgender men is a viable method that can significantly improve the participation and acceptance of cervical cancer screening in a LMIC setting. HPV testing may reduce the number of unsatisfactory results generated when using Pap smears as a screening method.
Creating an Electronic Health Record-Based Tool for Tracking of Abnormal Cervical Cancer Screening Results
Sangini Sheth1, Caitlin Sculley2, Nitu Kashyap1, David Liu2, John Sinard1, Karen Brown2, Karen Otterson3, David Roth3, and Linda Fan1. 1Yale School of Medicine, 2Yale New Haven Health, 3Yale Health Plan
Objective: To develop an electronic tracking system to facilitate surveillance of abnormal cervical cancer screening results in order to improve patient safety, quality of care, and workflow efficiency in a large hospital system.
Methods: A multidisciplinary team was formed with clinicians from various obgyn and primary care settings, pathologists, and experts in health information technology (HIT). The team used stakeholder engagement, workflow analysis, and HIT and the existing electronic health record (EHR) system to develop an electronic tracking system for abnormal cervical cancer screening.
Results: The team met over 9 months in 2016–2017 to identify existing workflows for cervical cancer screening, and to develop and test new electronic tracking tools. Three complementary tools were developed: 1) modifiers within the “Health Maintenance” section of the EHR for clinicians to activate that identify patients with abnormal results requiring surveillance, 2) a customized interface between the pathology information system and EHR to send discrete data elements for cytology and HPV results, and 3) EHR-based workbench reports with data from the first two components along with other relevant data to be used as a tracking system. In October 2017, a workbench report from an early adopter hospital-based obgyn clinic showed 29% of abnormal results did not have the Health Maintenance section updated one month after implementing the tool compared with 19% of abnormal results 3 months after implementation.
Conclusions: A novel, comprehensive tracking system for abnormal cervical cancer screening embedded in an existing and widely used EHR platform was successfully developed for a large hospital system. Following implementation, high utilization of the new tool can be achieved.
Development of an LMIC-Adapted Thermoablation Device
Miriam Cremer1, Karla Alfaro2, Mauricio Maza2, Albert Zevallos3, Luis Taxa3, Ana Celia Uriarte4, Philip Castle5, Todd Alonzo6, Rachel Masch2, Gabriel Conzuelo2, Montserrat Soler2, Julia Gage7, and Juan Carlos Felix8. 1Cleveland Clinic, 2Basic Health International, 3Instituto Nacional de Enfermedades Neoplasicas, 4Instituto Salvadoreño del Seguro Social, 5Albert Einstein College of Medicine, 6University of Southern California, 7National Institutes of Health, 8Medical College of Wisconsin
Objective: Thermoablation has emerged as a viable alternative to cryotherapy in the treatment of cervical pre-cancer. However, protocols differ by probe tip size, shape and temperature. We modified the most widely-used device in collaboration with the manufacturer to meet the needs of low-resource settings.
Methods: Twenty-one patients aged 25–65 scheduled for hysterectomy for indications other than cervical pathology underwent thermoablation with a 16 mm flat tip at 120 °C for 40 seconds. In a second study, the probe tip was reshaped and 25 patients underwent thermoablation with a 20 mm conical tip at 100 °C for 40 seconds. Participants verbally rated pain during treatment on a scale of 0 (no pain) to 10 (worst pain). Subsequently, cervical samples were obtained by cone biopsy and prepared for routine histological processing. Depth of tissue necrosis was measured at its deepest point by expert pathologists.
Results: Initially, mean depth was 2.7 mm (SE = .26) in the anterior lip and 2.5 mm (SE = .15) in the posterior lip. After the tip was modified, mean depth increased to 4.0 mm (SE = .22) in the anterior lip (p < .001) and to 3.8 mm (SE = .19) in the posterior lip (p < .001). Pain intensity was similar in both studies at 3.1 (SE = .43) vs. 3.4 (SE = .35) (p = .53).
Conclusions: Treatment with the 20 mm conical tip at 100 °C resulted in greater depth of necrosis than the 16 mm flat tip at 120 °C. Further research is needed to determine the optimal treatment approach. Standardized guidelines for thermal ablation will eliminate variation in technique.
Evaluation of Folate Receptor-Mediated Staining Solution for Referral for Positive Triage in Cervical Cancer Screening
Yun Zhao2 and Mena Farag1. 1GY Highland Biotech LLC, 2Peking University People's Hospital
Objective: To evaluate the performance of the Folate Receptor-Mediated Staining Solution (FRD™) for detection of cervical high grade lesions and as the referral for positive triage in cervical cancer screening.
Methods: 1504 patients who had abnormal cytology results or/and positive human papilloma virus (HPV) test in primary screening from August, 2012 to September, 2013, were selected from Peking University People’s Hospital and other 12 top III hospitals. The FRD™ was applied in all the patients in this study to compare the detection rate, sensitivity, specificity, and coincidence rate with HPV and cytology test according to the results of the cervical biopsy.
Results: The detection rate of FRD™ increased with the severity of cervical lesion. The sensitivity of HPV, cytology test and FRD™ was 95.54%, 80.39%, and 77.72%, respectively, and the specificity was 14.95%, 30.12%, and 60.02%, respectively. To triage the HPV HC2 positive population, the coincidence rate of FRD™ (62.66%) was higher than cytology ≥ ASCUS (48.61%). The colposcopy referral rate of cytology as a triage & FRD™ as a triage was 78.56% (425/541) and 57.49% (311/541), thus the colposcopy referral rate decreased 21.07%. To triage the ASCUS population, the coincidence rate of FRD (63.45%) was higher than cytology ≥ ASCUS (35.92%). The colposcopy referral rate of HPV test as triage & FRD™ as triage was 90.13% (429/476), 49.58% (236/476), thus the colposcopy referral rate decreased 40.55%.
Conclusions: The FRD™ is a simple, easy to operate, and is more inclined to detect the high grade cervical lesion. It could be used in the triage of HPV positive population and ASCUS population. It is worthy of clinical application in low-resource settings.
Evaluation of Outcomes for Implementation of an HPV-Based Screen and Treat Program in a Low-Middle Income Country
Karla Alfaro1, Mauricio Maza1, Philip Castle2, Todd Alonzo3, Andrea Chacon4, Juan Carlos Felix5, Jane Kim6, Julia Gage7, and Miriam Cremer8. 1Basic Health International, 2Albert Einstein College of Medicine, 3University of Southern California, 4El Salvador Ministry of Health, 5Medical College of Wisconsin, 6Harvard School of Public Health, 7National Institutes of Health, 8Cleveland Clinic
Objective: To review findings and evaluate lessons learned from the Cervical Cancer Prevention in El Salvador (CAPE) program, a public, 3-phase HPV test-based regional intervention centered on rural women.
Methods: After ascertaining higher treatment follow-up rates at 6 months for screen-and-treat vs. colposcopy-based screening in previous phases (Phase I: 98.3 vs. 68.8%, n = 2288; Phase 2: 88% vs. 44%, n = 8050), screen-and-treat was scaled-up to reach 20,000 additional women aged 30–59. Women were invited by health promoters to schedule screening appointments at community clinics. Those who tested positive were contacted to receive results and undergo visual triage (VT); eligible women were treated with cryotherapy at the same visit. Ineligible women were referred for colposcopy and appropriate follow-up.
Results: In the third phase, 17,965 women (89.8% of the target) were screened. All samples were processed using a low-cost HPV test. Positivity rates were 12.3%, compared to 11.9% in Phase I and 11.4% Phase 2 in the screen-and-treat modality. Among positive women, 85.14% (1,667/1,958) received immediate cryotherapy and 14.86% (291/1,958) were referred to colposcopy because lesions were too large or suspicious for invasive cancer.
Conclusions: CAPE demonstrates the feasibility of large-scale deployment of a screen-and-treat strategy with existing Ministry of Health resources. This approach can increase follow-up in underserved populations. In the final scale-up, positivity rates increased and treatment completion follow-up rates remained stable. The experiences gained during CAPE provide valuable insights for low- and middle-income countries planning to introduce HPV testing as part of public cervical cancer control programs.
Evidence That Most Post-Colposcopy Patients Are at Low Risk of Cervical Cancer/Precancer
Maria Demarco1, Li Cheung1, Walter Kinney2, Nicolas Wentzensen1, Tom Lorey2, Barbara Fetterman2, Nancy Poitras2, Brian Befano3, Philip Castle4, and Mark Schiffman1. 1National Cancer Institute, 2Kaiser Permanente Northern California, 3Information Management Services Inc., 4Albert Einstein College of Medicine
Objective: Women referred to colposcopy clinic are often viewed as a “high risk” population, even when the initial colposcopy/biopsy shows < CIN2. To inform impending post-colposcopy guidelines, this analysis examined the subsequent risk of CIN3+ among women with < CIN2 colposcopy results, taking into account the referring results that brought them to colposcopy and cotest results post colposcopy.
Methods: We analyzed 111,480 women aged 25–65 in surveillance post-colposcopy at Kaiser Permanente Northern California. We estimated absolute risks of CIN3+ among women: 1) recommended for colposcopy (pre-colposcopy), 2) in the subset of those with colposcopy and histology results < CIN2 (post-colposcopy), and 3) in those with cotest results post-colposcopy (return cotest).
Results: The 3-year risk of CIN3+ in the subset of women under surveillance post-colposcopy was 2%, much lower than the overall risk for all women recommended for colposcopy (8%). Return negative cotest results 1-year following colposcopy identified a large group (54%) of women who, based on their CIN3+ risk (e.g., <0.2% at 3 years following the post-colposcopy cotest), are comparable to women with normal cytology in the screening population. The value of cotesting compared with HPV testing alone might be most prominent among women with continued HPV positivity, to distinguish those at highest risk of precancer.
Conclusions: Most women under surveillance post-colposcopy are at low risk of subsequent CIN3+ and many might not need yearly surveillance. We need further discussion of risk thresholds, and the clinical value of cotesting vs HPV testing alone especially for women who continue to be HPV-positive in post-colposcopy surveillance.
p16/Ki67 Dual Staining Improves the Detection Specificity of High Grade Cervical Lesions
Li Geng1, Ruiyi Zhang1, and Xuefei Ge1. 1Peking University Third Hospital
Objective: To investigate the specificity of p16/Ki67 dual staining in the detection of high grade cervical lesions.
Methods: A total of 223 patients were enrolled with an average age of 39 years old. All samples were detected by p16/Ki67 immunocytochemical dual staining, Liquid-based cytology and High-risk HPV test. And each patient had histopathological diagnosis.
Results: The specificity of p16/Ki67 dual staining was 68.33%, which was significantly higher than that of cytology 38.33% and 21.67% of high-risk HPV (P <0.05), and p16/Ki67 dual staining had similar sensitivity with HR-HPV test for CIN2+ detection (90.18% vs 93.87%, P = 0.286). In triage cases of ASC-US and LSIL liquid-based cytology, the specificity of p16/Ki67 double staining was significantly higher than that of HPV test(66.67% vs 3.70%, P <0.05) and its sensitivity was similar to that of HPV test. The sensitivity and specificity of dual staining for CIN2+ detection in triage of HR-HPV positive women were 90.85% and 70.21% which were higher than those of cytology (83.01% and 42.55%) and HPV16/18 test(70.59% and 44.68%).
Conclusions: p16/Ki67 dual staining could improve the specificity of high grade cervical lesions detection and have similar sensitivity to HPV test. When triaging women with ASC-US or LSIL liquid-based cytology, or positive HR-HPV, by p16/Ki67 dual staining, the specificity of lesion detection was increased. p16/Ki67 dual staining could reduce colposcopy referalls and avoid excessive diagnosis and treatment.
Performance of Two Alternative Treatments for Cervical Pre-Cancer Against Standard Gas-Based Cryotherapy
Montserrat Soler2, Miriam Cremer1, Karla Alfaro2, Mauricio Maza2, Albert Zevallos3, Luis Taxa3, Ana Celia Uriarte4, Philip Castle5, Todd Alonzo6, Rachel Masch2, Gabriel Conzuelo2, Julia Gage7, and Juan Carlos Felix8. 1Cleveland Clinic, 2Basic Health International, 3Instituto Nacional de Enfermedades Neoplasicas, 4Instituto Salvadoreño del Seguro Social, 5Albert Einstein College of Medicine, 6University of Southern California, 7National Institutes of Health, 8Medical College of Wisconsin
Objective: Gas-based cryotherapy, the standard treatment for cervical pre-cancer in low-resource settings, is problematic due to the need for cryogenic gas. To develop alternative treatments, we compared depth of necrosis (DON) and patient pain associated with gas-based cryotherapy, CryoPen® (a gasless cryotherapy device), and thermoablation.
Methods: Subjects were 126 women aged 25–65 scheduled for hysterectomy for indications other than cervical pathology. Patients were randomly assigned to five arms: single-freeze CO2 cryotherapy (Arm A), double-freeze CO2 cryotherapy (Arm B), single-freeze CryoPen (Arm C), double-freeze CryoPen (Arm D), and thermoablation applied at 100 °C for 40 seconds (Arm E). Pain was reported verbally on a scale of 0 (no pain) to 10 (worst pain). The deepest necrosis point in cervical samples was measured and recorded.
Results: Mean DON (in mm) achieved by all treatments was above our pre-determined benchmark of 3.5: A = 4.9 (SD = 2.0), B = 5.6 (SD = 1.3), C = 4.9 (SD = 1.6), D = 4.5 (SD = 1.2), E = 4.1 (SD = 1.1). Reported pain levels ranged from 1–8 and mean pain per treatment was A = 1.7 (SD = 0.8), B = 2.2 (SD = 1.0), C = 2.5 (SD = 1.4), D = 2.5 (SD = 1.4), and E = 3.4 (SD = 1.7).
Conclusions: CryoPen® and thermoablation achieved non-inferior DON to standard cryotherapy. Pain levels were tolerable for all treatments, although somewhat higher with thermoablation. Quality control is underway and results will be updated accordingly. These new treatments are potentially viable alternatives to the current standard of care.
Pooled Risk Estimates of CIN2+ and CIN3+ by Strata of Cytology, HPV16/18, and Colposcopy Impression
Michelle Silver1, Jeff Andrews2, Julia Gage1, Michael Gold3, Michelle Khan4, L. Steward Massad5, Rebecca Perkins6, Mark Schiffman1, Katie Smith7, and Nicolas Wentzensen1. 1National Cancer Institute, 2BD, 3Tulsa Cancer Institute, 4Kaiser Permanente Northern California, 5Washington University School of Medicine, 6Boston Medical Center, 7University of Oklahoma
Objective: In the United States, cervical cancer screening strateegies include colposcopy as a follow-up to certain abnormal results. As screening shifts to Pap/HPV cotesting or primary HPV testing, the volume and underlying risk of women referred to colpocopy will change dramatically. Thus, a precision medicine approach to triage and management is needed that accounts for varying levels or risk among a colposcopy referral population. We calculated pooled risk estimates for all possible combinations of cytology, HPV, and colposcopy impression of all currently available data to provide the basis for such targeted recommendations.
Methods: We performed a systematic review and meta-analysis to calculated stratum-specific pooled risk estimates. Eligible studies must have included colposcopic impression and either cytology results or HPV16/18 genotyp results as well as a histologic biopsy diagnosis for adult women. Abstracts were reviewed using an abstraction sheet to capture information on the following risk markers: cytology, HPV status with partial genotyping, and colposcopy impression, as well as age, number of women, and number of CIN2, CIN3, and cancer cases.
Results: We calculated the risk of CIN2+ and CIN3+ based on cytology, colposcopy, and HPV16/18 test results. We found a similarity in risk patterns across studies such that risk estimates were similar within strata despite different referral populations and study designs. Our results also demonstrated the rarity of extreme combinations such as normal or acetowhite colposcopies with HPV16/18+ and/or HSIL+, regardless of the referral strategy.
Conclusions: Our results provide support for a precision medicine approach to triage and management of cervical cancer screening at the lowest and highest risk levels. Women with a normal colposcopy impression (no acetowhitening), <HSIL cytology, and HPV16/18 negative are at low risk of prevalent precancer, and therefore do no require targeted biopsies. Our calculations also support immediate excisional treatment for the highest risk women (at least two of the following: HSIL cytology, HPV16 and/or HPV18 positive, high-grade colposcopy impression).
Risk Factors for Failing Cervical Cancer Screening in Occult Invasive Cervical Carcinoma at Time of Simple Hysterectomy
Tara Castellano1, Lisa Landrum1, and Kathleen Moore1. 1Oklahoma University HSC
Objective: To determine risk factors associated with inappropriate cervical cancer screening and/or risks for false negative screens in those with occult invasive carcinoma (OICC) at the time of simple hysterectomy for benign indications.
Methods: Single-institution retrospective review from 1990–2017 of subjects with OICC at the time of hysterectomy done for benign indications. Baseline demographics, pre-operative evaluations, histopathologic characteristics, and treatment and outcome data were recorded. Failures in following screening guidelines vs those with false negative screening were identified. Fisher Exact tests for association were performed to assess for independent risk factors according to age, insurance status, and histology for each class.
Results: 59 subjects with median age of 44 years (range 30–82) were identified. Abnormal uterine bleeding was the most common indication for hysterectomy (57%, n = 34) and cervical dysplasia was in 41% (n = 24). Of those with inappropriate screening, 35% (n = 16) didn’t have documented pap smear, 20% (n = 9) had inappropriately managed pap, 15% (n = 7) had colposcopy but not conization, and 21% (n = 10) had LEEP that wasn’t managed appropriately. False negative screening occurred in 22% (n = 13) subjects. There was no significant association with age, insurance status, or histology to risk of false negative screening or inadequate screening.
Conclusions: The most common cause of OICC at the time of simple hysterectomy was failure to adhere to screening guidelines. Less frequently, false negative screening was the cause. No independent risk factor in either group was able to be identified in this small single institutional study. Illustrated is the importance of continuing education of referring surgeons regarding adequate cervical dysplasia screening in the preoperative evaluation for benign hysterectomy.
Survival of Older Women With Cervical Cancer: What Is the Impact of Screening History?
Rachel Kupets1, Mitchell Clark1, Nathaniel Jembere1, Li Wang1, Lilian Gien2, Danielle Vicus2, and Joan Murphy1. 1Cancer Care Ontario, 2Sunnybrook Health Sciences Centre
Objective: A population level retrospective cohort study to determine the influence of cervical screening history on the survival from cervical cancer in women 50 and older.
Methods: Women aged 50 and over diagnosed with invasive cervical cancer in Ontario, Canada between 2005–2012 and followed up until 2016. Screening history was observed for the 5 years prior to diagnosis. Health care administrative databases were linked to determine demographic, affiliation with primary care physicians, stage (available 2010–12), treatment and survival data. Kaplan meier and multivariate analyses were carried out to evaluate the impact of cervical screening on survival.
Results: 1938 women aged 50 and over were diagnosed with invasive cervical cancer between 2005–2012. 748 women were screened within the 5 years prior to diagnosis (median age 59) compared to 1190 not screened (median age 64). Of the screened women, 42.9% presented with stage ≥ II and 69.3% of unscreened had advanced disease. Four year overall survival (OS) was significantly greater in the screened group: 75.3% (CI: 71.9-78.1) vs. 53.3% (CI: 50.5-56.1%). In our univariate analysis, screening was significantly related to survival (HR 2.1, p < 0.01). In our multivariate analysis after adjusting for age, treatment, affiliation with primary care and income, screening was still significantly associated with improved survival(HR 1.59, p < 0.01).
Conclusions: Our results demonstrate a survival benefit to cervical cancer screening in women aged 50 and over who are diagnosed with cervical cancer. Cervical cancer screening participation must be encouraged in women older than 50 as screening rates decline in this age group.
Use of HPV Genotyping in Primary HPV-Based Cervical Cancer Screening: A Study Among 10,762 HPV-Infected Women
Maria Demarco1, Noorie Hyun1, Tina R. Raine-Bennett2, Barbara Fetterman2, Tom Lorey2, Nancy Poitras2, Brian Befano3, Philip Castle4, Julia Gage1, Nicolas Wentzensen1, and Mark Schiffman1. 1National Cancer Institute, 2Kaiser Permanente Northern California, 3Information Management Services Inc., 4Albert Einstein College of Medicine
Objective: HPV testing is now recommended for primary cervical screening, but infection is common, necessitating triage methods to prevent overtreatment. We studied HPV genotyping for prediction of whether an HPV-positive test poses a risk of present or imminent precancer, or will likely “clear” if followed.
Methods: We typed 10,762 residual cervical specimens from HPV-infected women aged 30–65, tested as part of clinical cotesting between 2007–2011, and followed for up to 8.5 years in the NCI-Kaiser Permanente Northern California Persistence and Progression (PaP) study. Using a competing risk model, we estimated absolute risks of clearance, progression, or persistence.
Results: By year 3, most infections had cleared and a small percentage had caused precancer; long-term persistence was rare. Absent progression, viral clearance did not vary substantially by type. Risk of progression to CIN2+ differed substantially by type, with HPV16 conveying qualitatively highest and sustained risk (2.6% at 1 year and 5.5% at 3 years, with progression continuing throughout follow-up). The 12-type “other high risk” HPV group could be stratified into intermediate and low risk groups (with 1-5% versus <1% risks at 3 years); unlike HPV16, rate of progression slowed for the least carcinogenic types.
Conclusions: Distinguishing HPV16 is plainly valuable to predict precancer among HPV-positive women. The risks of HPV18 and HPV45 (disproportionately important for invasive cancer) cannot be properly assessed without even longer follow-up. The clinical usefulness of further HPV genotyping needs to be assessed relative to other triage strategies, to determine how long to wait for clearance before treatment.
Clinical Utility Pilot Study of a Novel Tissue-Trap Brush in Histologic Sampling of the Cervical Transformation Zone
Juan Felix2, Marc Winter1, and Neal M Lonky3. 1Orange Coast Women's Medical Group, 2Medical College of Wisconsin, 3University of California, Irvine
Objective: Multiple or random colposcopic biopsies in high risk cohorts with abnormal screening is preferred by the ASCCP. Locating the site for random sampling is both focal and not systematic. We evaluated the biopsy utility and experience of a novel tissue sampling brush to obtain diagnostic samples from the entire transformation zone of the cervix, “in-vitro” and “in-vivo”.
Methods: This is an IRB approved prospective colposcopy case cohort study in two settings: 1. Laboratory simulation (JF) of a colposcopic transformation zone biopsy and 2. Clinical use during colposcopy (MW) 1. A fresh discard hysterectomy specimen stained with 5 histologic dye colors (four quadrants and endocervix). 1 and 2: The brush head was moderately pressed on the central cervix and rotated 360 degrees clockwise and counter-clockwise. The brush head was detached, placed in formalin, and processed identically to conventional curettage specimens. Diagnostic quality and evaluation of the patient and clinician observed patient pain and cervical bleeding, as well as ease of use was evaluated (Likert Scale).
Results: Laboratory, and clinical use (6 cases) showed tissue excavation from all aspects of the cervical transformation grossly (Figure 1). The brush-trapped tissue samples in 6 cases (mean age 38.8 yrs) was consistently abundant and diagnostic (Figures 1 and 2), histologically trans-epithelial reaching into stroma with all 5 stain colors evident histologically in-vitro, with minimal in-vivo pain (mean 1.2/10) and bleeding (mean 1.8/10) with high ease of use documented.
Conclusions: This FDA compliant biopsy brush removes and traps diagnostic samples from the entire cervical transformation zone without aaparent trauma and could be considered for random sampling. Its correlation to loop excision pathology grade is being evaluated.
Comparison of Contrast Mediators on the Accuracy of a Pocket Colposcope in U.S., Peru, and Sub-Saharan Africa
John Schmitt1, Jenna Mueller1, Christopher Lam1, Jenna Peters1, Yannet Daniel1, Nimmi Ramanujam1, and Bariki Mchome2. 1Duke University, 2KCMC
Objective: Our goal is to create a tele-colposcopy platform for medically underserved regions both locally and globally. We previously reported on a portable pocket colposcope that allows for low-cost, high quality VIAM of cervical cancer precursors. We now focus on comparing acetowhitening, vascular features, and iodine uptake imaged with the pocket colposcope to determine what combination provides the highest accuracy for static image evaluation, by experts via SMS.
Methods: Images have been obtained from more than 500 patients in the U.S., Peru, and Sub-Saharan Africa using pairs of contrast mediators. Expert colposcopists provided a semi-quantitative evaluation in a blinded, randomized manner, classifying each image as normal, low grade dysplasia, high grade dysplasia, and suspicious for cancer. Results were compared to pathology when available.
Results: Blinded images read by three or more expert colposcopists showed high concordance (80-90%) between the pocket colposcope and a high-end colposcope for detection of VIAM positive results. When comparing specifically to pathology, images captured with the pocket colposcope and a high-end colposcope agreed 69% for acetic acid images, 72% for acetic acid and green light images, and 83% for acetic acid and Lugol’s iodine images.
Conclusions: This preliminary analysis suggests that the level of agreement between devices as well as pathology increased when expert colposcopists had access to additional sources of contrast. We recently collected 150 images using a combination of acetic acid, Lugol’s iodine and vascular imaging and analysis is underway. Our expectation is that using all three sources of contrast will be superior to paired contrast mediators.
Detecting Cervical Cancer Precursors in Women With ASC-US Cytology: Standard Colposcopy vs Digital Colposcopy With DSI
Karen E. Harris1, Mark D. Akin2, Emmanouil Papagiannakis3, and Sara DeNardis4. 1Unified Women’s Clinical Research Gainesville, 2Austin Area OB-Gyn, 3DYSIS Medical, 4University of Central Florida
Objective: To analyze detection of CIN3+ on women referred with ASC-US cytology.
Methods: IMPROVE-COLPO was an observational study of US community-based colposcopy. One arm recruited consecutive women examined with digital colposcopy and adjunctive dynamic spectral imaging (DSI). A control arm collected cases from preceding consecutive colposcopies with conventional methods (by the same colposcopists). The primary measure of this analysis was the number of women with CIN3+ histology on biopsy among ASC-US (persistent/HPV+) referrals. Secondary measure was the method and efficiency of detection.
Results: The study recruited 1327 retrospective and 1204 prospective patients with ASC-US, seen by 144 colposcopists at 41 clinics. Baseline characteristics and percentages of patients that were biopsied were comparable, but the average number of biopsies taken from biopsied patients increased from 1.43 to 1.72 in the prospective group. Colposcopic biopsy detected CIN3+ in more women who underwent colposcopy with DSI compared to those who did not. 30 (2.26%) women in the retrospective and 48 (3.99%) in the prospective arm were found with CIN3+ (p = 0.015, two-sided Fisher exact test), a 60% relative increase. Biopsy was less efficient in the retrospective arm, with 42.4 biopsies taken per CIN3+ case detected, vs. 30.3 in the prospective arm. The sensitivity of standard colposcopic impression was low in both arms (<10%), but in the prospective arm, when incorporating the DSI map, it reached 73%.
Conclusions: Colposcopic biopsy detected, at first appointment, significantly more cervical precancers in women who underwent colposcopy with DSI compared to those who did not.
Impact of Using Electrical Impedance Spectroscopy (EIS) on the Performance of Colposcopy in Diagnosing HSIL
John Tidy2, Charles Muszynski1, Benoit Vaysse1, Emma Ghib1, Segolene Delmas-Lanta1, Fabrice Sergent1, and Jean Gondry1. 1CHU Amiens-Picardie, 2Sheffield Teaching Hospitals
Objective: To compare the efficacy of colposcopy plus EIS (ZedScan) for detecting intraepithelial high-grade lesions compared to colposcopy alone.
Methods: Prospective study conducted at a University Hospital colposcopy clinic, CHU Amiens-Picardie, France. Patients referred following abnormal cervical cytology or colposcopic follow up were examined by colposcopy plus ZedScan to assess the cervix. Two colposcopists took part in the study. The results of ZedScan directed and colposcopically directed biopsies were compared.
Results: 91 patients were included. Median age was 33 (23–61) years. 80 (88%) were referred with abnormal cytology; low grade 72.5%, high grade 15.4% and 12% follow-up post conisation or colposcopic follow up. 30 had high grade disease, colposcopy alone detected 19 high-grade lesions. ZedScan increased detection of high grade lesions by 47.4% (p=0.01), identifying 28 high grade lesions including one case of invasive cancer. Two cases were missed by colposcopy and ZedScan, one with a TZ3 lesion. The increase in detection of high grade disease in women referred with low grade cytology was 50%. 56 women underwent biopsy, the number of biopsies per woman biopsied was 1.14 for colposcopy and 1.26 for colposcopy and ZedScan. The sensitivity and NPV for colposcopy were 61.3% and 81.7% and 93.3% and 91.3% for ZedScan. A combination of normal colposcopy practice and ZedScan had a sensitivity and NPV of 100%. No adverse events were reported.
Conclusions: ZedScan used in conjunction with the colposcopy improves sensitivity in detecting high-grade lesions at the expense of a slight increase in the number of biopsies.
Implementation of a Research-Robust Colposcopy Management Registry Program Within the Electronic Medical Record
Neal Lonky1, Nancy Cannizzaro1, Alicia Castaneda1, Tanya Stowe1, Sumi Hawk1, LanFang Xu2, and Chun Chao1. 1Kaiser Permanente, 2MedHealth Statistical Consulting
Objective: We recently deployed a colposcopy management registry that includes a Smart Form used during diagnostic, follow-up and therapeutic visits related to cervical neoplasia. The goals of this innovative tool, embedded within the electronic medical record (EMR), are to (1) streamline care, (2) standardize documentation, (3) facilitate communication between clinicians, nurse coordinators and patients, and (4) enable research to guide evidence-based practice. Here we described the experience and findings of the pilot deployment.
Methods: The colposcopy registry was developed in Clarity platform and integrated in the Kaiser Permanente (KP) EPIC EMR system. The registry was piloted as standard clinical work flow among 12 colposcopists at KP Orange County Medical Center, California since July 2017. The registry cues colposcopists to document, with user friendly boxes/buttons (Figure 1), the following information: patient clinical and sexual history, colposcopic practices, diagnostic approach and management decisions. Documentation includes crucial variables traditionally not readily extractable, such as age at sexual debut, lifetime sexual partners, age at first HPV vaccination, number/locations of lesions and biopsies, and histologic results.
Results: To date, the colposcopists efficiently completed records for 423 patients (median age 38.0 years; 39% white/61% non-white) and 445 visits (54% Diagnostic, 37% Follow-up, 8% Therapeutic). Detailed data on patient history, colposcopic findings and practice are automatically integrated into the EMR and available for analysis.
Conclusions: The pilot program facilitates systemic effective clinical care and communication and provides a data repository for retrospective comparative effectiveness research. Quality assurance and cost effectiveness audits may also be performed, defining a new value driven colposcopy care delivery system.
Increased Detection of Adenocarcinoma In Situ (AIS) by Electrical Impedance Spectroscopy (EIS)
John Tidy1, Brian Brown2, Jamie Healey1, and Julia Palmer1. 1Sheffield Teaching Hospitals, 2University of Sheffield
Objective: To establish the performance of colposcopy with EIS (ZedScan) in women referred with abnormal glandular cytology or diagnosed with AIS (high grade glandular intra-epithelial neoplasia (HG-CGIN)). To evaluate the electrical impedance spectra associated with AIS.
Methods: A prospective cohort study of women undergoing both colposcopic and ZedScan examination as part of the investigation of an abnormal cervical cytology result.
Results: 42 women were referred with cytology showing either AGC/glandular neoplasia (16), AGUS/borderline changes in endocervical cell (26). 25 were found to have SIL/CGIN, of whom 23 had HSIL/AIS. A further 10 women were found to have CGIN (9 had AIS) on biopsy or LEEP following investigation of an abnormal squamous cytology sample or clinical indication. There were 18 cases of pure AIS. 89% of HSIL/AIS was detected by a colposcopic impression of high grade disease and a positive ZedScan result. 90% of pure AIS was detected by a colposcopic impression of high grade disease and a positive ZedScan result. Four cases of pure AIS were detected only by a positive ZedScan result. EIS data for pure AIS is different from normal glandular tissue but similar to HSIL.
Conclusions: EIS can separate AIS from normal glandular epithelial. The performance of colposcopy in detection of AIS has previously been shown to be poor with sensitivity of 10% and 87% having a normal colposcopic impression. ZedScan identified 89% of AIS cases compared with 72% for colposcopy.
Correlation Research of Vaginal Microecology, HR-HPV and Cervical Intraepithelial Neoplasia
Ying Hong1, and Ying Hong1. 1Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
Objective: To investigate the relationship among vaginal microecology, high risk human papilloma virus (HPV) infection and Cervical intraepithelial neoplasia(CIN) to provide new idea for preventing cervical cancer.
Methods: 460 cases of outpatients of Nanjing Drum Tower Hospital from June,2016 to June,2017.162 of them were diagnosed with CIN and HPV positive (CIN and HR-HPV infection group) While 107 of them were no more than HPV positive with normal TCT results or colposcopy results (HR-HPV infection group).191 of them were normal women(control group). Among all 269 HPV infected women, some were tested negative in the HC2 test despite their positive results in the HPV genotyping. We therefore divided them into the HPV-HC2≥1 group and the HPV-HC2<1 group. Among all 269 HPV infected women, some were tested negative in the HC2 test despite their positive results in the HPV genotyping. We therefore divided them into the HPV-HC2≥1 group and the HPV-HC2<1 group.We analyzed the relationship among vaginal microecology, HPV infection and CIN.
Results: The incidence rates of the imbalance of vaginal microecology in the CIN and HR-HPV infection group, the HR-HPV infection group and the control group were 54.9% (89/162),35.5%(38/107) and 29.8% (57/191),with significant differences (P<0.05). The incidence rates of the imbalance of vaginal microecology in the HR-HPV infection group and the control group were not significantly different(P>0.05). The H2O2 and PH values in the CIN and HR-HPV infection group were higher than those in the HR-HPV infection group (P<0.05). The H2O2 and PH values in HR-HPV infection group and control group were not significantly different(P>0.05). The incidence rate of the imbalance of vaginal microecology in the HPV-HC2≥1 group 53.2% (109/205) was higher than that in negative HPV-HC2 group)(P<0.05). The incidence rate of the imbalance of vaginal microecology between the control group and the HPV-HC2≥1 group were significantly different(P<0.05). The incidence rate of the imbalance of vaginal microecology between the control group and the HPV-HC2<1 group were not significantly different(P>0.05).(4)The H2O2 and PH values in the HPV-HC2≥1 group were higher than that in the HPV-HC2<1 group (P<0.05). The H2O2 and PH values between the control group and the HPV-HC2<1 group were not significantly different(P>0.05).
Conclusions: The incidence of vaginal microecology and high load HR-HPV were closely related to the CIN. The incidence of vaginal microecology,especially changes of lactobacillus and PH,were risk factors of high load HPV infection.
Histopathologic Follow-Up and HPV Testing of ASC-US Pap Test in China’s Largest Academic Woman’s Hospital
Xiang Tao1, Hao Zhang1, Jianan Xiao1, Xianrong Zhou1, Li Wang1, and Chengquan Zhao2. 1Obstetrics and Gynecology Hospital of Fudan University, 2University of Pittsburgh Medical Center
Objective: Atypical squamous cells of undetermined significance (ASC-US) report rate and related parameters are critical in quality control of cervical cytology. The study investigated histopathologic outcomes as well as HPV testing for patients with ASC-US Paps in China’s largest women hospital.
Methods: A retrospective cohort study documented ASC-US Pap tests, age, HPV results, and histopathologic follow-up from 2011–2016 in the database of our hospital. Pap test methods include ThinPrep, SurePath and conventional Pap (CP) and HPV test methods include HC2, Cervista, and cobas 4800.
Results: During the study period, 1,095,022 Pap tests were performed. Overall ASC-US reporting rates was 3.0%, significantly higher in liquid-based cytology (LBC) (3.3%) than that in CP (1.2%), and relatively higher in teenagers (4.7%) and the women aged 60 years and above (5.0%). Of 6,836 ASC-US cases with HPV tests, overall HPV positive rate was 46.1% (HC2, 40.0%; Cervista, 56.6%; Cobas 44.8%; P<0.05). Among 13,746 ASC-US cases with histopathologic follow-up within 6 months, invasive cancer, CIN2/3, and CIN1 were detected in 0.8% (109 patients), 2.7%, and 25.6%, respectively. 1,890 cases with ASC-US/HPV+ and 1,774 cases with ASC-US Pap/HPV- had histological follow-up results within 6 months. CIN2/3 and CIN1 detection rates were significantly higher in HPV positive group than that in HPV negative group (table). Table Histopathologic follow-up results for women with ASC-US/HPV testing results, by different ages.
Conclusions: Our HPV positive rate of ASC-US Pap test was higher than that in the most labs in the USA. We were surprised to find that 4.0% women with ASC-US/HPV- had high grade cervical squamous lesion, including 4 cases of invasive squamous carcinoma, in immediate follow-up. The study results indicate that HPV test as the primary screening is not an appropriated approach in the current China.
HPV Screening and Management
Algorithm Models for Extended Genotyping Applications in High-Risk HPV Screening and Persistence Tracking
Jeff Andrews1 and Charles Cooper1. 1BD Diagnostics
Objective: Current SGO and ASCCP guidelines include recommendations for positive results of limited genotyping (16/18). Meijer criteria and VALGENT validation of HPV extended genotype (xGT) assays testing have been met by four assays. xGT for all hrHPV genotypes may be considered by future guideline panels.
Methods: Two principles for cervical cancer screening and management were accepted: programs will be risk-based; similar management for similar risk. The prevailing USA action thresholds for retesting in 12 months and referral to colposcopy were accepted. The current best evidence for risk of CIN3+ by genotype and cytology results was applied under 3 screening paradigms: cytology with HPV triage, cotesting, and primary HPV with cytology triage. The hierarchical method for assigning mixed infections to the genotype with highest positive predictive value was accepted. The discriminated risks were applied against the accepted action thresholds to generate algorithmic decision trees.
Results: Algorithmic decision trees are presented for ASCUS triage, LSIL triage, cotesting, and primary HPV with cytology triage, utilizing hrHPV xGT and cytology risk prediction. There are three possible actions: return to routine screening, retest in 12 months, and refer to colposcopy. There are 84 possible combinations of hierarchical hrHPV xGT results and cytology results; when sorted into 3 action bands, the test results are grouped in tiers.
Conclusions: The NCI and ASCCP have published collaborative plans to develop new decision support tools that utilize big data and mobile applications. Static decision tree algorithms may be replaced by these new modalities; in the interim, algorithms can support modeling and inform debate.
Clinical Utility of Detecting Human Papillomavirus (HPV) DNA in Urine Samples Including HPV 16 and 18/45 Genotyping
Radha Padhy1 and Adi Davidov1. 1Staten Island University Hospital
Objective: To detect high-risk human papillomavirus (hrHPV) DNA in urine samples and compare their concordance with hrHPV DNA in cervical samples including HPV 16 and 18/45 genotyping
Methods: Urine samples were collected from 123 women who had cytology results from the following groups: (1) abnormal and hrHPV positive, (2) normal and hrHPV positive, and (3) normal and hrHPV negative. Positive urine samples were genotyped for HPV 16 and 18/45. Samples were analyzed using mRNA reverse-transcriptase mediated amplification technology and the APTIMA HPV assay.
Results: A higher proportion of patients with abnormal cytology and hrHPV positivity had positive urine samples (41%; 17/41) versus patients with normal cytology and hrHPV positivity (32%; 10/41). The concordance rate was substantial between cervical and urine samples (k=0.75, CI: 0.71-0.80, P<0.005) with an overall percent agreement of 55%. The sensitivity of urine detection was 33% and specificity was 100%. The PPV of urine detection was 100% and NPV was 43%. There were no false positives detected. The prevalence of HPV in urine samples was equal (40%) in patients with benign histology versus CIN 2/3 histology on colposcopy (p=0.71). Of the cervical samples that had HPV genotyping, 25% (3/12) were positive for the same HPV genotype in the urine. The genotype-specific concordance for HPV 16 and 18/45 was 100% for all the urine samples when compared to the cervical samples.
Conclusions: The utility of mRNA reverse-transcriptase mediated amplification methodology is suboptimal in detecting hrHPV DNA in urine samples and therefore cannot be used for primary cervical cancer screening.
Concordance of Self- and Clinician-Collected Anorectal Swabs for HPV Detection in HIV-Negative Men Who Have Sex With Men
Nicholas Yared1, Keith Horvath1, Jason Baker1, and Shalini Kulasingam1. 1University of Minnesota
Objective: To determine the concordance of self-collected and clinician-collected anorectal swabs for the detection of human papillomavirus (HPV) DNA in a population of HIV-negative men who have sex with men (MSM).
Methods: Self-collected anorectal swabs obtained by participants using illustrated instructions were compared with subsequent clinician-collected swabs. Swabs were tested for type-specific HPV DNA. Categories of HPV types detected by both approaches were compared. Sensitivity and specificity of self-collection was calculated assuming clinician-collection as the gold standard.
Results: Seventy-eight participants had paired swab samples of adequate quality for analyses. Results are shown in Table 1. Table 1. Pairwise Comparisons of HPV DNA Prevalence For Self- and Clinician-Collected Anorectal Swabs Self-Collected, n (%) Clinician-Collected, n (%) p-value Sensitivity Specificity ______________________________________________________________ ______________________________________________________________ Any HPV 54 (69.2%) 57 (73.1%) 0.440 84.2% 71.4% Any HR-HPV* 33 (42.3%) 43 (55.1%) 0.012 69.8% 91.4% 4v HPV† 16 (20.5%) 23 (29.5%) 0.034 60.9% 96.4% 9v HPV‡ 25 (32.1%) 33 (42.3%) 0.090 62.5% 89.1% HPV Type 16 3 (3.8%) 8 (10.3%) 0.024 37.5% 100% HPV Type 18 3 (3.8%) 5 (6.4%) 0.159 60% 100% __________________________________________________________________ __________________________________________________________________ *HR-HPV = High-risk HPV types †4v HPV = 4-valent HPV vaccine types (6, 11, 16, 18) ‡9v HPV = 9-valent HPV vaccine types (6, 11, 16, 18, 31, 33, 45, 52, 58)
Conclusions: Self-collected anorectal swab samples showed lower sensitivity but moderate-to-high specificity for detection of high-risk and vaccine-preventable HPV types compared to clinician-collected swab samples. Self-collection instructional details may have impacted sensitivity and specificity, suggesting a need to optimize and standardize instructions.
Continuity of Care Heuristic Model for Sequential HPV Testing Over 3 Tests With Limited or Extended Genotyping
Jeff Andrews1 and Charles Cooper1. 1BD Diagnostics
Objective: Current guidelines focus on the point of care and a single screening encounter. Management guidelines include 1–2 rounds follow-up of abnormal results. In the real world, care of women involves continuity of care and serial testing.
Methods: The current best evidence was utilized for the natural history of HPV infection, clearance, reactivation, persistence, progression, and regression. The concepts of sexual debut, opt-in vaccination, and new exposure were utilized. A continuity of care extending for 3 testing occasions was selected. A heuristic algorithm was built to describe all possible testing results and underlying infection and disease over the continuity of care period.
Results: A heuristic algorithm graphic is presented with footnotes explaining the elements. Two tables are presented for all the modeled continuity of care results over 3 serial tests, applied to the 2012 ACS, ASCCP, ASCP screening guidelines for the prevention and early detection of cervical cancer and the 2012/2013 ASCCP consensus guidelines for the management of women with abnormal cervical cancer screening tests. The first table reports limited genotyping (16/18), yielding 8 possible results over 3 serial tests; the second presents results using extended genotyping, yielding 14 possible results over 3 serial tests.
Conclusions: Future guideline panels may choose to consider continuity of care and serial testing as an aspect of clinical decision making tools. A model for the natural history of HPV infection and the possible permutations supports the guideline panelist and stakeholder considerations.
Determining the Optimal Cervical Carcinoma Screening Method in HIV Positive and HIV Negative Cambodian Women
Lena Goldstein3, Sovannara Thay1, Andrew Goldstein2, Kruy Lim1, and Chanthou Seang1. 1Sihanouk Hospital Center of HOPE, 2Center for Vulvovaginal Disorders, 3McDonogh School
Objective: Logistical and economic issues make traditional cytology-based cervical cancer screening challenging in developing countries. Alternative screening strategies must be developed to screen millions of women in resource poor countries.
Methods: 250 Cambodian women (129 HIV+, 121 HIV-) underwent four alternative screening methods: 1) Self-sampled HPV testing (careHPVTM system, Qiagen, Maryland), 2) clinician-collected HPV testing, 3) Visualization with Acetic Acid (VIA) and 4) Digital Cervicography (DC) with the EVATMSystem (MobileODT, Israel).
Results: 56 of the 250 women tested positive for high-risk HPV (hrHPV). Self-sampling identified 50/56 (89%) whereas physician obtained specimens only identified 45/56 (80%). 36 women were VIA+ [23/129 (17.8%) HIV+], [13/121 (10.7%) HIV-]. 28 of the VIA+ underwent confirmatory biopsies (24 CIN1, 4 CIN2) [8 patients refused confirmatory biopsy]. DC was able to differentiate between high-grade (HGD) and low-grade dysplasia in all 28 women who had biopsies.
Conclusions: CareHPVTM allows rapid and inexpensive detection of HR+. The patient obtained samples detected more hrHPV than did provider obtained specimens. DC with EVATM was able to distinguish between low and high-grade cervical dysplasia and is therefore superior to VIA without adding significantly to the time or cost of screening. DC also allows women with probable HGD to have a LEEP rather than cryotherapy. DC is superior to VIA as images can be used for documentation, quality control, and telemedicine consultation. This study suggests that a combination of self-sampling HPV testing and subsequent DC of hrHPV+ women can be an efficient and cost-effective see-and-treat cervical cancer screening strategy.
HPV45 Why Does It Matter? Clinical Utility in Risk-Stratified Cervical Cancer Screening & Management: Systematic Review
Jeff Andrews1. 1BD Diagnostics
Objective: Cross-sectional prevalence studies reported a higher proportional risk of HPV 45 prevalence in cervical cancers than prevalence in CIN3 or NILM. This phenomenon is termed enrichment. Prevalence studies of adenocarcinoma reported a proportionally higher prevalence of HPV 45 in adenocarcinoma, compared to overall invasive cervical cancer. Prospective clinical trials and retrospective studies of preserved samples could supplement the prevalence data to determine prognostic risk discrimination utility of HPV 45, and provide evidence needed by screening guideline panels.
Methods: PubMed, Cochrane Database of Systematic Reviews, and Health Technology Assessment database were searched from 2001 through 2017 for relevant studies. Hand-searching of retrieved article reference lists was used to supplement the search. Eligible studies included prospective studies of women and retrospective studies of residual specimens from women that were screened or tested using HPV tests that reported HPV 45 individually. The reference standard was CIN2, CIN3, CIN2+, CIN3+, AIS, or invasive cervical cancer. The timeframe for screening paradigms was baseline, 1-year, 3-year, 5-year.
Results: A PRISMA flow diagram is presented for this systematic review. Seventeen original research articles met inclusion and exclusion criteria. Reporting HPV 45 results provides discrimination of both current and future CIN2+ risks. HPV 45 risks are compared to HPV 18 risks under the principle of equal management for equal risk. HPV 45 identification during screening could be utilized for risk discrimination and to permit follow-up of type-specific persistence, to support risk-based clinical decisions.
Conclusions: Guideline panels must decide on recommendations for HPV 45 results. Models for different screening paradigms are described.
Impact of Patient Directed Cytology Results Correspondence Program on Appropriate Management of High Grade Cytology
Rachel Kupets1, Simon Tavasoli2, and Eli Kane2. 1Toronto-Sunnybrook Regional Cancer Center, 2Cancer Care Ontario
Objective: Proper follow-up of High Grade (HG) Pap test result is critical to the prevention of cervical cancer. The purpose of this study was to evaluate the impact of a patient based results correspondence program on appropriate and timely follow-up of HG Pap test among at risk women aged 21–69 in Ontario, Canada.
Methods: A cohort study with a historical control was used to investigate the impact of a result letter on adherence to follow-up after a HG Pap test. Analyses were conducted in an intention-to-treat basis. The intervention group was defined as women with a HG Pap test in 2014–2016 and the control group included women with a HG Pap test in 2010–2012. Follow-up was defined as a colposcopy or related treatments within 6 months of a HG Pap test. Factors that might influence adherence to follow-up were included as covariates in a multivariable logistic regression model.
Results: The study population comprised of 7,088 women in the intervention group and 6,887 women in the control group. Follow-up rate in the intervention group was 86.2% compared to 81.0% in the control group. Controlling for covariates, women in the intervention group were more likely to have a follow-up (AOR=1.4, 95% CI 1.3–1.6). Other significant factors included being registered to a specific family physician and physician’s gender.
Conclusions: The patient based correspondence program which provides cytology results directly to the woman has reduced loss to follow-up for a HG abnormality with an increase in colposcopy and appropriate treatments.
Improving Follow-Up and Treatment of HPV Positive Women in Guatemala’s Public Medical System
Francesca Holme1, Claudia Camel2, Rose Slavkovsky1, Jose Jeronimo3, and Silvia de Sanjose1. 1PATH, 2Instancia por la Salud y el Desarollo de las Mujeres, 3The Global Coalition Against Cervical Cancer
Objective: Guatemala is implementing HPV testing to screen for cervical cancer in four provinces. Follow-up and treatment of HPV-positive women has been a challenge for the public medical system. Our aims were to support the Ministry of Health (MOH) to improve follow-up and treatment rates and document successful strategies.
Methods: We worked with MOH officials to streamline patient management algorithms, engage local leadership in follow-up decision-making, contact HPV-positive women by deploying health care personnel to their homes, advocate for municipal governments to sponsor procurement of cryotherapy gas, and introduce thermal coagulation as a non-gas-dependent treatment option. We used MOH data to assess follow-up and treatment rates before and after these interventions and assembled field- worker observations to understand how different interventions contributed to improvements.
Results: Follow-up and treatment rates improved from a baseline of 63.6% and 47.0%, respectively, in December 2015, to 74.2% and 84.7% in June 2017. Most significant improvements occurred in provinces where follow-up and treatment were set as priorities, patient algorithms were simplified to eliminate the triage step, and thermal coagulation was implemented.
Conclusions: Follow-up and treatment rates for HPV-positive women can be improved in the context of a public medical system in a lower-middle-income country. A combination of proactive leadership, appropriate policy, and supportive technology yielded the greatest improvements in the Guatemalan context. Other low- and middle-income countries facing barriers to follow-up of screen-positive women in cervical cancer prevention programs can learn from the Guatemalan experience.
Long Term Risk Prediction of p16/Ki-67 Dual Stain in Triage of HPV-Positive Women
Megan Clarke1, Barbara Fetterman2, Philip Castle3, Mark Schiffman4, Eric Stiemerling2, Diane Tokugawa2, Nancy Poitras2, Walter Kinney1, Tom Lorey2, and Nicolas Wentzensen4. 1,2Kaiser Permanente Northern California, 3Albert Einstein College of Medicine, 4National Cancer Institute
Objective: HPV cervical cancer screening requires triage markers to distinguish who should be referred to colposcopy. p16/Ki-67 dual stain (DS) cytology has previously shown good risk stratification for triage of HPV-positive women. We evaluated the long-term risk prediction of DS in a large population of HPV-positive women.
Methods: 1,509 HPV-positive women screened with HPV/cytology co-testing were enrolled in 2012. DS cytology was performed on residual Surepath material and slides were evaluated for DS positive cells. Cervical endpoints were ascertained from the clinical database with follow-up through 2017. We conducted a Kaplan Meier analysis to estimate risk of CIN3+ by DS and cytology compared to clinical management thresholds.
Results: Baseline risk of CIN3+ in DS positives was 13.9% and 2.7% in DS negatives. For ASC-US+, risk was 12.4% and 2.9% for NILM. The 5-year risk of CIN3+ in DS positives was 20.4% and 4.9% in DS negatives. For ASC-US+, 5-year the risk was 16.8% and 6.7% for NILM. Among DS negatives, the risk remained below the colposcopy referral threshold for 5 years while in women with NILM cytology, the colposcopy referral threshold was crossed after year 3.
Conclusions: In the first study evaluating long-term risk stratification of p16/Ki-67 DS, DS negativity provided reassurance against CIN3+ for at least five years. In contrast, the risk in women with negative cytology results exceeded the colposcopy referral threshold after three years. These data support use of DS for triage of HPV-positive women with the possibility of extending surveillance intervals compared to cytology.
Prevalence of Insufficient Pap Smears in an OBGYN Resident Teaching Clinic
Nia Thompson1, Eliza Rodrigue1, Markeiya Polite1, and Stacey Holman1. 1LSUHSC
Objective: The Pap Smear is the primary cervical cancer screening tool. On average 2% of pap smears collected are insufficient/unsatisfactory, leading to missed diagnoses, increased healthcare burden, and patient inconvenience. Red blood cells, vaginal atrophy, inflammation, proteinaceous material, neoplasia, and provider error are the most common reasons for insufficient samples. In the resident teaching clinic, a 4-fold increased rate of unsatisfactory results prompted investigation.
Methods: Pap smear data collected from the University Medical Center - New Orleans resident clinic from January to June 2017 were reviewed by the Cytopathology department. Insufficient specimens were identified with reasons cited including inflammation, scant cellularity, obscured by lubricant or blood, atrophic pattern, thick preparation, or a combination of the above reasons. The classifications were further stratified by provider post graduate year.
Results: 691 pap smears were reviewed with an 8.1% (n=56) unsatisfactory rate. Scant cellularity (35.7%), blood (33.9%), and lubricant (10.7%) were the leading causes of insufficiency. Less common causes (<10%) were inflammation, atrophy, and thick preparation. PGY 1 residents accounted for more than half (52.7%) of insufficient pap smears.
Conclusions: Educational opportunities are being initiated for all level residents and nurses in the clinic. We hope to provide information that will decrease rates of insufficient Pap smear results. In conjunction with the Cytopathology department, education on specimen collection will be implemented and tracking of results will continue after education is complete.
Effectiveness of Human Papillomavirus (HPV) Vaccine Against HPV16/18-Positive High-Grade Cervical Lesions
Julia Gargano1, Michelle Johnson Jones1, Linda Niccolai2, Marie Griffin3, Ina Park4, Nancy Bennett5, Melissa Powell6, Angela Cleveland1, Troy Querec1, Elizabeth Unger1, and Lauri Markowitz1. 1CDC, 2Yale School of Public Health, 3Vanderbilt University Medical Center, 4University of California at San Francisco School of Medicine, 5University of Rochester School of Medicine and Dentistry, 6Oregon Health Authority
Objective: To estimate HPV vaccine effectiveness (VE) against vaccine-type cervical lesions by timing of vaccination and birth cohort.
Methods: We analyzed data on histologically confirmed cervical intraepithelial neoplasia (CIN) grades 2–3 and adenocarcinoma in situ (CIN2+) collected via population-based surveillance in five U.S. communities, 2008–2014. Archived diagnostic specimens from cases age-eligible for vaccination were tested for 37 HPV types. Intervals between dates of first vaccination and screening that led to diagnosis were categorized as <1/unvaccinated, 1–11, 12–23, 24–35, 36–47, and ≥48 months. We compared vaccination history between HPV16/18-positive and HPV16/18-negative CIN2+ cases using logistic regression, adjusting for site, insurance, and race, overall and stratified by birth cohort (1979–1986, 1987–1995). VE was estimated as 1-adjusted odds ratio (aOR).
Results: We included data on 1569 HPV16/18-positive and 1749 HPV16/18-negative CIN2+; 341 and 595 had a vaccination-to-screening interval ≥1 month. HPV16/18-positive CIN2+ had significantly lower aOR for vaccination 24–35, 36–47, and ≥48 months before screening (aOR=0.56 [95% CI 0.40-0.80], 0.39 [0.27-0.58], and 0.24 [0.18-0.33]) than HPV16/18-negative CIN2+; VE was 44%, 61%, and 76%, respectively. No significant VE was seen with vaccination-to-screening intervals <24 months. Women born in 1987–1995 had higher VE than women born in 1979–1986 (≥48 month interval: aOR=0.16 [0.11-0.25], VE=84% for 1987–1995; aOR=0.41 [0.27-0.63], VE=59% for 1979–1986 cohort).
Conclusions: Significant effectiveness against vaccine-type lesions was evident when vaccination was initiated ≥24 months before abnormal screen result. VE was higher with longer vaccination-to-screening intervals, and in younger cohorts (initiated vaccination median 19 years) than in older cohorts (initiated vaccinated median 23 years).
HPV Vaccination Status and Attitudes Towards HPV Vaccination Among Low Income, Urban Women Undergoing Colposcopy
Mary Duarte Thibault1, and Kimberly Gecsi1. 1University Hospitals Cleveland
Objective: Multiple factors influence HPV vaccination uptake including physician recommendation, friend or family member endorsement, and parental acceptance. The objective of this study was to explore the relationship between HPV vaccination status and attitude towards HPV vaccination of one’s future male and female children in women with known cervical cytologic abnormalities undergoing colposcopic examination.
Methods: A survey was administered to women who underwent colposcopic examination in a resident-run, urban, Medicaid-based clinic at a tertiary care university hospital. Survey measures included HPV vaccination status, reason for receiving or not receiving the vaccine, previous history of abnormal cervical cytology, obstetric history, and anticipated plan for HPV vaccination of any current or future children.
Results: Of the 40 patients surveyed, only 7 (17.5%) had received at least 2 doses of the vaccine. Of the women who did not receive the vaccine, 25% cited “I did not think I needed the vaccine” and 14.3% cited “my parent did not want me to get the vaccine” as reasons for not getting vaccinated. Thirty-two percent of women did not associate HPV vaccination with cervical cancer prevention. The majority of women had at least one child and most intended to vaccinate their female and male children (75.7% vs 73.7%).
Conclusions: Education about vaccination is needed to improve uptake, especially in this population. The colposcopic exam is an opportunity to educate parents about vaccination of the next generation.
Uptake of HPV Vaccination in High-Risk Vulnerable Women: Intersection of Reproductive Health and Preventative Care
Jessica Madrigal1, Lisa Henry-Reid1, and Ashlesha Patel1. 1John H. Stroger, Jr. Hospital of Cook County
Objective: We aimed to determine HPV vaccination rates in women presenting for reproductive health services and to identify facilitators and barriers to vaccination.
Methods: Women between 13 to 25-years-old who presented for abortion care at a county hospital in 2015–2016 had a one-on-one encounter with a health educator about sexually transmitted infection (STI) prevention. A health interview was conducted to gather information on history of STI testing and HPV vaccination. Information collected included age, race/ethnicity, and education. Contingency tables and log-binomial regression modeling were used to estimate prevalence ratios and determine factors associated with receipt of HPV vaccine.
Results: We completed health interviews with 4,039 women during the study period. On average, women were 21 (SD=2.3) years old, 89% African American, and 76% had Medicaid insurance. Overall, 25.3% (n=1,020) had previously received the HPV vaccine. Roughly half of these women (n=570; 55.9%) reported receiving three doses of the vaccine. A majority of women (n=3,200) reported having received STI testing in the previous two years, and 74.5% (n=3,008) reported having a primary care physician. In an adjusted multivariable model, younger age, lower educational attainment, being uninsured, and not having a primary care doctor were significantly associated with being unvaccinated (p-values <0.0001 to 0.02).
Conclusions: Despite being in the appropriate age range for vaccination and reporting regular access to healthcare services, women presenting for abortion care in our clinic have low HPV vaccination rates. Abortion care settings may be a unique opportunity to offer and provide the first dose of vaccine for young women. Further collaboration between reproductive health and primary care providers may improve access and uptake of this vaccination in young women.
AGC Subclasses and Risk of Invasive Cancers: A Prospective Case Series Study
Xuezhi Jiang1, Laura E. Smith1, and Peter Schnatz1. 1Reading Hospital
Objective: Atypical Glandular Cells (AGC) is a rare Pap smear finding that is associated with a high rate of clinically significant disease. Previous research recognized an association between AGC and primary malignancies, but whether each AGC-subclass (Endocervical [EC], Endometrial [EM], or Not Otherwise Specified [NOS]) carries a similar risk of post-AGC invasive cancers has not been assessed. The objective of this study is to assess the risk of invasive cancers associated with Atypical Glandular Cell (AGC) subclasses.
Methods: A prospective case series was designed to identify cases of AGC through the pathology database at The Reading Hospital and Medical Center between 1/1/2005 and 6/1/2017. The AGC pathology report included patient’s age, date of initial AGC Pap, AGC subclass, provider, and cytopathologist recommendations. Additional information including demographics, pathologic and follow-up data was gathered by chart review via the Reading Hospital Electronic Medical Record System. A multivariate survival analysis was conducted using SAS; P<0.05 was deemed as statistically significant. Covariates adjusted in the survival analysis included age, body mass index (BMI), hypertension, diabetes, smoking, dyslipidemia, polycystic ovarian syndrome (PCOS), oral contraceptive use, and intrauterine device (IUD) use.
Results: Of the women diagnosed with AGC between 1/1/2005 and 6/1/2017 (n=656), 641 received at least one follow up visit. Mean (SD, median, min-max) follow up time after AGC diagnosis are 4.7(3.2, 5.2, 0.01-10.4) years. Of the 641 women who received a follow up visit, 397 received an endometrial biopsy and were classified into AGC subclasses AGC-EC (n =81, 20.4%), AGC-EM (n=141, 35.5%), AGC-NOS (n=175, 44.1%), and a total of 91 women (14.2%) were diagnosed with at least one invasive cancer post-AGC diagnosis. The majority of the 91 women had endometrial cancer (n=53), with the number of women diagnosed with breast (n=11), skin (n=9), cervical (n=8), thyroid (n=2), Hodgkin’s lymphoma (n=2), and other (n=6) cancers occurring at lower rates. Cochran-Armitage trend test showed that in the 397 women with endometrial biopsy after AGC diagnosis, the risk of endometrial cancer increased in a stepwise manner across AGC subclasses from AGC-EC, to AGC-NOS, to AGC-EM (p=0.0025). In addition, in the 641 women who received at least one follow up visit after AGC diagnosis, the risk of all invasive cancers increased in a stepwise manner across AGC subclasses from AGC-EC, to AGC-NOS, to AGC-EM (p=0.005). Log Rank test which analyzed time-to-endometrial cancer in women with endometrial biopsy (n=397) showed a distinct survival curve of AGC-EC from AGC-NOS and AGC-EM (p=0.014, Fig.1). Furthermore, Log Rank test which analyzed time-to-all invasive cancers in women with at least one follow up visit post-AGC (n=641) showed a distinct survival curve of AGC-EC from AGC-NOS and AGC-EM (p=0.012, Fig.2).
Conclusions: The incidence of AGC (0.2%) in our institution was similar to the incidence in previous reports. Each of the AGC subclasses carries a different risk for post-AGC endometrial cancers and all cancers. The risk profile of AGC-EC for developing and time-to-developing, post-AGC cancers is distinctly less severe than AGC-NOS and AGC-EM. 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 post-AGC malignancies across AGC subclasses from AGC-EC to AGC-NOS to AGC-EM. The risk profiles of AGC-NOS should not be underrated, thus AGC-NOS may warrant the similar initial workup as AGC-EM. Further large population based prospective studies are needed to confirm the study findings.
Coriolus Versicolor and Treatment of HPV (High Risk)
Margarita Riera Blasco1, Ruperez Perez Blas1, Isabel Lazaro Vicario1, Ana Felgueroso1, Esther Fontanet Perez1, and Ana Aguayo Alba1. 1ICCS Institut Català de la Salut
Objective: Objective: evaluate the efficacy of Coriolus Versicolor vaginal gel in patients with positive HPV (high risk).
Methods:− Target population: Patients who come to the cervical patology unit (positive HPV) for high risk between 20 and 65 years, regardless of the grade of cervical lesion and who have been treated with Coriolus Versicolor vaginal gel for three weeks and then alterning days until the next control at 6 months. From December 2016 to October 2017. Inclusion criteria: Patients between 20 and 65 years old with high-risk HPV with normal cytology or with cytologic diagnosis of ASCUS, ASC-H, L-SIL, H-SIL (CIN II-III) as well as patients with a history of cervical conization. - Exclusion Criteria: patients vaccinated with Bivalent, Tetravalent or Nonavalent vaccine, and pregnant patients. - Retrospective descriptive observational study: We performed controls to determinate the HPV-high-risk by hybrid capture, cytology, colposcopy and biopsy (if applicable) following the protocols of the ICO (Instituto Catalán de Oncología). Study with authorization was performed. - We introduce the cases in database and we obtain the following results:
Results: Total patients: 91 -HPV + with cytology lesion 46 (50.5%) -HPV + with normal cytology 45 (49.5%) ASCUS: 17 (18.6%) Normalize 11 (64.7%) Are worse 3 (17%) Persistence degree of injury 3 (17%) L-SIL: 19 (20.8%) Improve or normalize 13 (68.4%) Worsted 1 (5.2%) Persistent degree of injury 5 (26.3%) H-SIL: 10 10.8% Persistence degree of injury 9 (90%) Worsted 1 (10%) HPV clearance are 53 cases (58.2%) in total, with pathological cytology 24 (52.1%) and with normal cytology 29 (64.4%).
Conclusions: CONCLUSIONS Coriolus Versicolor vaginal gel appears to be effective against ASCUS and L-SIL lesions caused by high-risk HPV. It is not effective in diagnosed H-SIL lesions. In HPV positive patients with normal cytology, there is a clearance of the virus at 6 months after starting treatment.
Prevalence of Concurrent or Previous High-Grade CIN in Women With High-Grade AIN and or Anal Carcinoma
Crystal Reese1, Evelyn Reynolds1, Emily Wang1, and Michelle Uzor1. 1Morehouse School of Medicine
Objective: The incidence of anal carcinoma has grown 2.2% each year over the last ten years among women from the United States. 1 In a study by Coffey et al., a historical diagnosis of cervical intraepithelial neoplasia (CIN) 3 was the strongest predictor of risk of anal cancer in women aged 50 or above.2 Human papilloma virus (HPV) infection is the major inciting factor for both CIN and anal intraepithelial neoplasia (AIN).3 While the majority of HPV anal infections clear, persistent anal dysplasia is a precursor to anal cancer 4. There continue to be few studies in heterosexual women, even though they are more likely to be affected by anal carcinoma. Objectives:
- Determine prevalence of previous or concurrent high-grade cervical intraepithelial lesion (CIN 2 and 3) in women diagnosed with high-grade anal intraepithelial neoplasia or anal carcinoma
- Determine prevalence of high risk HPV positivity in women with both high-grade cervical and anal intraepithelial neoplasia or anal carcinoma
Methods: Institutional review board approval was obtained. We conducted a chart review of patients seen in the Grady Health System from January 1, 2006-December 31, 2015. Inclusion criteria was women over the age of 18 diagnosed with AIN 2/3 or anal carcinoma. We then reviewed those records for documentation of the patient’s Pap smear history, any colposcopic procedures, and any treatment for cervical dysplasia including cervical excisional biopsy Charts without a previously documented Pap smear, colposcopy, cervical excisional biopsy for treatment of cervical dysplasia were excluded from the analysis. We also reviewed the included charts for a documented high risk HPV test and demographic information including HIV status, age, race, and smoking status. Data analysis was completed by Morehouse School of Medicine Biostatistics Department. Descriptive statistics were used to summarize the data. Mean with standard deviation was used for continuous variables and frequency with percentage was used for categorical variables.
Results: We identified 53 patients with the diagnosis of high-grade anal dysplasia or anal carcinoma during the study time period. Fifty-two patients, or 98.1%, of our study population were Black or African-American. Of the 53 patients, 16 had a previous or concurrent diagnosis of high-grade cervical dysplasia for a prevalence rate of 30.2%. We had data on high-risk HPV positivity on XX patients. The overall prevalence rate of past high risk HPV positivity in these women with high-grade cervical and anal intraepithelial neoplasia or anal carcinoma was 31.3%. Of the 16 patients with a history of cervical dysplasia, 87.5% were HIV+.
Conclusions: Currently, there are no standardized guidelines to screening for anal dysplasia or carcinoma. This may be in part because to date there no randomized clinical trials demonstrating the efficacy of any screening method. However; due to the increase in the incidence of anal carcinoma, some experts have advocated screening certain high-risk populations (such as women with prior CIN, HIV positive patients, and men who have sex with men) with anal pap smears and high-resolution anoscopy with anal pap smears or anoscopy. men who have sex with men) with anal pap smears and high-resolution anoscopy. In our study population the majority of the women with concurrent CIN and AIN or anal cancer (87.5%) were co-infected with HIV. Thus, there is a definite role for screening HIV-positive women for both cervical and anal dysplasia. We plan to conduct a prospective study of women with high-grade cervical dysplasia and cervical cancer to determine the rates of concurrent anal dysplasia, to begin to address the question of whether all women with these diagnoses should routinely be screened.
Undeserved Populations (Transgender, Homeless, Native American, etc)
Anal Cancer Risk Factors and Utilization of Anal Pap Smear Screening Among Transgender Persons
Lydia Fein1, Adriana Wong1, Isabella Rosa Cunha1, Brian Slomovitz2, and JoNell Potter1. 1University of Miami Miller School of Medicine, 2Sylvester Comprehensive Cancer Center
Objective: To identify risk factors for and understanding of anal cancer and associated screening tests among transgender persons.
Methods: An anonymous survey was designed and distributed with SurveyMonkey.com to transgender persons recruited at health fairs, surgical clinics, and self-referral by word of mouth. Descriptive statistical analysis was performed.
Results: 24 transgender women (TGW), age 23–67 years old (mean=42) and 13 transgender men (TGM), age 18–59 years old (mean=29) participated. The majority were Caucasian [TGW, 15 (63%); TGM, 12 (92%)], and insured [17(71%) TGW; 10 (77%) TGM]. Reported risk factors for anal cancer included smoking history [(14 (58%) TGW; 7(54%) TGM], past STI diagnosis [9(38%) TGW; 1(8%) TGM], HIV positivity (1(4%) TGW), receptive anal intercourse [17(71%) TGW, 7(54%) TGM], and inconsistent condom use [10(42%) TGW; 7(54%) TGM]. Only 4(17%) TGW perceived themselves to be at risk for anal cancer. Most TGW reported little to no knowledge of anal cancer (16, 67%) or anal pap smears (18, 75%). While five (21%) reported past screening, most expressed willingness to undergo future testing (n=19, 79%). Among TGM, only two (15%) perceived themselves to be at risk for anal cancer; five (38%)were familiar with anal pap smears; and only one (8%) person reported past testing. Eight (62%) reported willingness for future screening.
Conclusions: Transgender persons have multiple risk factors for anal cancer, yet self-perceived risk is low. Most are unfamiliar with anal cancer screening and have not been tested. This suggests transgender persons would benefit from increased awareness of anal cancer risk and screening methods.
Cervical and Anal Cancer Screening in Transgender Individuals
Lauren Abern1 and Karla Maguire1. 1Harvard Vanguard Medical Associates
Objective: Transgender individuals face many barriers to care. As a result, they can be hesitant to seek health care. The goal of this study is to evaluate barriers to care, determine rates of cervical and anal cancer screening, and if this screening was addressed by providers.
Methods: Transgender patients ages 21–64 participated in an online survey which included demographics, medical history, and perceptions of the healthcare system.
Results: 99 transgender men and 24 transgender women completed the survey. Mean age of transgender men was 28.8 (SD 10), and women 39.0 (SD 16). The majority of transgender men and women were white (84%, 91%), had private health insurance (71%, 58%) and graduated from college (54%, 58%). 29 (66%) transgender men reported having had cervical pap smears, and 1 (2%) an anal pap smear. Providers discussed a need for cervical pap smears with 60% and anal pap smears with 11% of transgender men. Transgender women have not had anal pap smears 0 (0%). Providers did not discuss need for pap smear of the anus with transgender women. Of the respondents, 90 (73%) experienced barriers to care. The majority (78, 87%) reported cost as a factor while 52 (58%) had problems with access to care.
Conclusions: Many transgender people face barriers to care that can limit their ability to access screening for cervical and anal cancer. Educational interventions for both physicians and patients are needed to ensure screening and follow up are performed for this community.
Findings of a Cervical Cancer Screening and Prevention Clinic at the University of Buea, Cameroon
Cortney Eakin1, Rodrigue Ekollo, MD2, Derick Nembulefack2, Gregory Halle-Ekane2, Gracious Tangui3, R. Brady4, and David Greenspan5. 1Maricopa Integrated Health Sys, 2University of Buea, 3Cameroon Baptist Convention Health Services, 4St. Joseph Hospital, 5University of Arizona
Objective: To determine the prevalence of precancerous lesions among a university-based population in the Southwest region of Cameroon.
Methods: In this pilot program, a public-private partnership was established between the University of Arizona, University of Buea and the Cameroon Baptist Convention Health Services (CBCHS). A one-day screening clinic using visual inspection with acetic acid (VIA) and Lugol’s solution (VILI) was provided at the University Student Health Center. Screening impressions were documented as negative, low-grade, high-grade or suspicious for cancer. Thermocoagulation was available for low-grade lesions. LEEPs were arranged for high-grade lesions. University faculty, staff and students were invited.
Results: Among 114 patients screened, three (2.6%) were HIV positive. The majority were married (51%) and had 0–2 sexual partners in the past 5 years (65%). One patient had received HPV vaccination. One hundred and seven patients (93.9%) were negative. Of those that were screen positive, six (5.3%) had low-grade lesions and one (0.9%) had a high-grade lesion. Five low-grade lesions were treated with thermocoagulation with one not treated due to young age. One screen negative patient had LEEP performed as recent pap smear was suspicious for cervical adenocarcinoma. Thus, two patients underwent LEEP.
Conclusions: Cervical cancer is the second leading cause of cancer deaths in women in Cameroon. The prevalence of precancerous lesions among our screened population was 6.14%. All lesions were successfully treated and adequate follow-up was arranged. This study validates the success of public-private partnerships in establishing cervical cancer screening and treatment programs in low-resource regions.