Journal of Lower Genital Tract Disease

Increases in Human Papillomavirus Testing Preceding Diagnosis of Cervical Precancer in 5 US States, 2008–2016

Objective The aim of the study was to describe trends in human papillomavirus (HPV) testing preceding diagnosis of cervical precancer during a time of changing screening recommendations. Materials and Methods We conducted a cross-sectional analysis of data from active, population-based, laboratory surveillance among 1.5 million residents of 5 areas in the United States. We included women aged 21–39 years diagnosed with cervical intraepithelial neoplasia grades 2, 2/3, or 3 or adenocarcinoma in situ (collectively, CIN2+) during 2008–2016, who had a cytology and/or HPV test before diagnosis (n = 16,359). Results The proportion of women with an HPV test preceding CIN2+ increased from 42.9% in 2008 to 73.3% in 2016 (p < .01); testing increased in all age groups (21–24 y: 35.3% to 47.6%, 25–29 y: 40.9% to 64.1%, 30–39 y: 51.7% to 85.9%, all p < .01). The HPV testing varied by cytology result and was highest among women with atypical squamous cells of unknown significance (n = 4,310/4,629, 93.1%), negative for intraepithelial lesion or malignancy (n = 446/517, 86.3%), and atypical glandular cells (n = 145/257, 56.4%). By 2016, at least half of all cases in every surveillance area had an HPV test before diagnosis. Conclusions During 2008–2016, the proportion of women with an HPV test preceding CIN2+ increased significantly for all age groups, cytology results, and surveillance areas. By 2016, most (85.9%) women aged 30–39 years had an HPV test, consistent with recommendations. Increasing utilization of HPV tests, which have demonstrated improved sensitivity for detecting cervical disease, may in part explain increasing rates of cervical precancer among women 30 years and older.

Management of Vulvar Cancer Precursors: A Survey of the International Society for the Study of Vulvovaginal Disease

Objective The aim of the study was to determine how experts treat vulvar high-grade squamous intraepithelial neoplasia (VHSIL) and differentiated vulvar intraepithelial neoplasia (dVIN). Method A 26-question survey was designed through a literature review, reviewed by the Survey Committee of the International Society for the Study of Vulvovaginal Disease (ISSVD), and distributed to all ISSVD members via e-mail in January 2019. Results Overall, 90 of 441 physician members consented to participate and 78 of 90 were eligible to complete the survey. Most respondents were gynecologists (77%), followed by dermatologists (12%). Forty-five percent responded that their pathology was being reported using the 2015 ISSVD terminology of vulvar squamous intraepithelial lesions. The most common first-line treatments were as follows: unifocal VHSIL—excision (65%), multifocal VHSIL—imiquimod 5% (45%), VHSIL in a hair-bearing area—excision (69%), and clitoral disease—imiquimod 5% (47%). In the recurrent VHSIL, excision was favored (28%), followed by imiquimod 5% (26%) and laser (19%). Differentiated vulvar intraepithelial neoplasia was most often first treated with excision (82%), and more patients were referred to gynecologic oncology. Most patients were seen in follow-up at 3 months (range: 1 week–6 months). Sixty-seven respondents provided 26 different ways to follow treated patients, which were most commonly every 6 months for 2 years and then yearly (25%), followed by every 6 months indefinitely (18%). Conclusions Treatment of VHSIL and dVIN varies among vulvar experts with excision being the most common treatment, except in multifocal VHSIL where imiquimod is commonly used. There is wide variation in how patients are followed after treatment.

Development of an Algorithm for Cervical High-Grade Squamous Intraepithelial Lesion Based on Breath Print Analysis

Objectives This study was designed to develop an algorithm for the diagnosis of cervical high-grade squamous intraepithelial lesions (HSIL), based on patterns of volatile organic compounds, evaluated using an e-nose. Methods For this pilot study, the study population consisted of a group of 25 patients with histologically confirmed HSIL and a group of 26 controls. Controls consisted of women visiting the outpatient department for gynecological complaints unrelated to cancer. Women had a negative high-risk human papillomavirus and/or normal cytology (negative for intraepithelial lesions of malignancy) of their most recent test performed in the context of participation in routine cervical cancer screening. Breath tests were performed and labeled with the correct diagnosis. Machine-learning techniques were used to develop a model for predicting HSIL. Based on the receiver operating characteristics curve, both sensitivity and specificity were calculated. Results Individual classifications of all patients with HSIL and controls, as calculated by the model, showed a sensitivity of 0.88 (95% CI = 0.68–0.97) and specificity of 0.92 (95% CI = 0.73–0.99). The positive predictive value and the negative predictive value were 0.92 (95% CI = 0.72–0.99) and 0.89 (95% CI = 0.70–0.97), respectively. The Cohen κ coefficient was 0.80. Conclusions E-nose can detect distinctive patterns of volatile organic compounds between cervical HSIL patients and controls. Validation of the algorithm in further studies is necessary before possible implementation into daily practice.

Cervical Cancer Among Women With HIV in South Carolina During the Era of Effective Antiretroviral Therapy

Objectives We aimed to determine whether women with HIV (WWH) and cervical cancer were more likely to experience cancer-related death and to be diagnosed with cervical cancer at a younger age and in more advanced stages. Materials and Methods This is a retrospective cohort study of all women diagnosed with cervical cancer in South Carolina from 1998 to 2018. Deidentified data were obtained from 2 statewide databases. A survival analysis was performed to evaluate differences in cancer survival between women with and without HIV. Wilcoxon rank sum test was used to determine differences in the median age at cancer diagnosis. χ2 test was used to assess differences in cancer stage according to HIV status. Results Four thousand three hundred fourteen women were diagnosed with cervical cancer, and 53 (1.2%) had HIV infection. Survival time in months was similar between WWH and HIV-negative women (86 months [interquartile range {IQR} = 32–146] and 62 months [IQR = 18–153], p = .37; log-rank p = .26). Compared with HIV-negative women, WWH were less likely to experience cervical cancer–related death (36% vs. 19%, p = .005). Women with HIV were diagnosed with cervical cancer at a younger age (44 [IQR = 37–54] vs. 49 [IQR = 39–61], p = .02). Cervical cancer stage was similar at diagnosis between groups (tumor node metastasis stage, p = .97, and Surveillance, Epidemiology, and End Results summary stage, p = .41). Conclusions Women with HIV were younger at diagnosis than HIV-negative women, but they were no more likely to die from or have more advanced cervical cancer. Women with HIV were not more likely to develop cervical cancer before the age of 21 years and earlier screening is likely unnecessary.

Applying Results of Extended Genotyping to Management of Positive Cervicovaginal Human Papillomavirus Test Results: Enduring Guidelines

Objective The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for the use of extended genotyping results in cervical cancer prevention programs. Methods Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated using data obtained with the Onclarity HPV Assay from large cohorts. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Risk estimates were reviewed in relation to clinical action thresholds and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group. Results Colposcopy is recommended after positive tests for human papillomavirus (HPV) types 16 and 18. For those positive for HPV 45, 33/58, 31, 52, 35/39/68, or 51 but negative for 16 or 18, triage with cytology or dual stain testing is recommended. When screening with primary HPV testing, for patients who test positive for HPV types 56/59/66 and no other carcinogenic types, repeat HPV testing in 1 year is recommended. When screening with cotesting, for those who test positive for HPV types 56/59/66 and no other carcinogenic types, 1-year return is recommended for negative for intraepithelial lesion or malignancy, atypical squamous cells of undetermined significance, and low-grade squamous intraepithelial lesion, and colposcopy is recommended for atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H), atypical glandular cells, high-grade squamous intraepithelial lesion, or carcinoma. When patients without prior high-grade cytology (atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, atypical glandular cells, high-grade squamous intraepithelial lesion, or carcinoma) or histology (cervical intraepithelial neoplasia [CIN]2, CIN3, or adenocarcinoma in situ) are being followed, use of extended genotyping results is acceptable. When high-grade cytology or histology results are present, or when patients are being followed after treatment of CIN2+, management using the 2019 guidelines is recommended. Conclusions Human papillomavirus extended genotyping can guide clinical management in the setting of a positive HPV test result.

Reduction in Unindicated Cervical Cancer Screening in Adolescents in a Large Health Care System

Objectives Evidence-based guidelines recommend against screening for cervical cancer (Pap testing) in average-risk adolescents <21 years old. Despite this, many still undergo unindicated screenings with subsequent detrimental reproductive health and economic consequences. The authors’ aim was to reduce unindicated cervical cancer screening in individuals <21 years old in a large health care system by utilizing an electronic provider notification. Methods Starting in July 2020, a Best Practice Advisory (BPA) appeared in the electronic medical record (EMR) if providers ordered Pap testing on individuals <21 years old. This BPA reiterated that screening was not indicated for average-risk adolescents and prompted users to choose an indication if they wanted to proceed. A retrospective chart review, pre/post intervention study was performed comparing individuals <21 years old with Pap testing performed before and after intervention (January 2019–June 2020 and July 2020–June 2021, respectively). Patient characteristics were extracted from the EMR and analyzed using Fisher exact tests, Kruskal-Wallis tests, and logistic regression. Results There were 140 subjects included: 106 preintervention and 34 postintervention. There were no differences in baseline characteristics. Neither Pap nor human papillomavirus testing results differed between the groups. Preintervention, 6.6% of cytology tests were indicated compared to 20.6% postintervention (p = .042). The proportion of indicated human papillomavirus testing did not differ preintervention and postintervention at 65% and 45%, respectively (p = .295). The overall reduction in unindicated cervical cancer screening postintervention was 13.9% (95% CI = 4.0–23.7). Conclusions The authors demonstrated that incorporating a BPA to the EMR reduces unindicated cervical cancer screening.

Understanding Sexual and Gender Minority Populations and Organ-Based Screening Recommendations for Human Papillomavirus–Related Cancers

Objectives Sexual gender minority (SGM) populations are at risk for human papillomavirus (HPV)–related cancers of the anogenital tract and oropharynx and often face barriers to health care. The goals of this document are to clarify language to provide inclusive care for SGM populations and to provide recommendations for screening and prevention of HPV-related cancers in SGM populations. Materials and Methods An expert committee convened by the American Society for Colposcopy and Cervical Pathology performed a narrative review of the literature through February 2023. A comprehensive MEDLINE database search was performed for relevant studies. The literature review was divided into categories by organ/topic and by SGM population. Given the variability in available data for several of the categories, recommendations were made based on national guidelines where appropriate or expert opinion where there were less data to support risk-based guidelines. Results Definitions and terminology relevant to SGM populations are presented. The authors advocate the adoption of sexual orientation gender identity data collection and an organ-based screening approach, which is possible with knowledge of patient anatomy, sexual behaviors, and clinical history. This includes screening for cervical cancer per national recommendations, as well as screening for anal, vulvar, vaginal, penile, and oral cancers based on risk factors and shared clinical decision making. The authors recommend consideration of HPV vaccination in all SGM individuals up to age 45 years old who are at risk. Conclusions An organ-based screening approach is part of a global strategy to create an inclusive care environment and mitigate barriers to screening and prevention of HPV-mediated cancers in SGM populations.

Cervical Cancer 2010–2019: An Upper Midwest Catchment of 40,000 Square Miles

Objectives American Indian (AI) women have a higher incidence and mortality from cervical cancer than non-Hispanic White (NHW) women in the US. This article’s purpose is to detail the clinical events in the cervical cancer prevention continuum among the AI and White women with cervical cancer on the US frontier. Materials and Methods A cancer center with a nearly 40,000 square-mile catchment area maintained a detailed cancer registry connected to the clinic records of all cervical cancer patients between 2010–2019. This catchment area provided records of both an AI and a White population. Descriptive and inferential statistics and modeling predictions detailed the prevention continuum. Results Among the 126 with cervical cancer, 20% were AI, and 78% were White. Sixty percent did not participate in cervical cancer screening within the 5 years before their diagnosis, and on average, 9.2 years passed since the last cervical cancer screening. 91% presented with symptoms, and most women presented with 2 or more symptoms. Thirteen percent underwent a colposcopic diagnostic step, significantly delaying the time to diagnosis compared to other diagnostic steps. Sixty-nine percent of the histopathologic diagnoses were squamous cell carcinoma, and 27% were adenocarcinoma. Forty-nine percent presented at stage I regardless of histopathology. Chemotherapy and radiation therapy were most commonly combined. Sixty-three percent of the population survived, and 42% survived at least 3 years from diagnosis. Younger age and earlier stages at diagnosis were the significant adjusted predictors of survival. Conclusions The authors’ detailed cervical cancer prevention continuum events provide new data questioning the use of colposcopy for women symptomatic at presentation.

Impact of Vulvar Cancer Surgery on Quality of Sex Life: A Review of Literature

Objectives Vulvar cancer is a gynecological cancer for which posttreatment morbidity must be known to propose the appropriate medical strategy. The objectives of this article were to review and to summarize the available studies evaluating the impact of vulvar surgery on the quality of sex life. Materials and Methods We searched MEDLINE abstracts (source PubMed) and included all studies published between 1990 and 2020 that evaluated the impact of vulvar surgery on the patients’ sex life. Articles were selected in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. We evaluated the quality of the studies using the “study quality assessment tools” established by the National Heart Lung and Blood Institute and the health-related quality-of-life score. Summary statistics were used to report the results of the studies selected. Results A total of 41 articles were screened, and 15 studies were included in this review. Two questionnaires, that is, European Organization for Research and Treatment of Cancer QLC C30 and Female Sexual Function Index, were used in 60% of the studies. The quality of the studies was heterogeneous. None of them had a high level of evidence. Eleven of the 16 studies reported an impairment of quality of sex life, mainly related to the size of the initial lesion and the type of surgery performed. Preoperative sexual status, that is, active sex life, age, and morbidity seemed to be important factors. Conclusions None of the studies had a high level of evidence, and their methodological quality was heterogeneous. More powerful studies using validated questionnaires are necessary. Because this is essential surgery, patients should be informed that if it impacts their sexual life, management strategies will be part of their postoperative care.

An Alternative to Cytology in Triaging Cisgender Men and Transgender Women With HIV for High-Resolution Anoscopy

Objectives To evaluate high-risk human papillomavirus testing (hrHPV) as an alternative for anal cytology in screening for high-grade anal neoplasia (AIN2–3) among males with HIV. To identify predictive risk factors for AIN2–3 and develop a clinical tool to triage males with HIV for high-resolution anoscopy (HRA) without cytology. Design Retrospective cohort study of 199 adult cisgender men and transgender women with HIV referred to an anal neoplasia clinic in the Southeastern United States between January 2018 and March 2021. Methods Each subject underwent cytology, hrHPV, and HRA. Clinical and sociodemographic risk factors were collected for each subject. Significant risk factors for AIN2–3 were identified using logistic regression, and a triage tool incorporating these factors was developed. Screening test characteristics were calculated for cytology with and without adjunct hrHPV, hrHPV alone, and the triage tool. Results In multivariate analysis, significant predictors of AIN2–3 were hrHPV positivity (odds ratio [OR] = 11.98, CI = 5.58–25.69) and low CD4 count (OR = 2.70, CI = 1.20–6.11). There was no significant difference in positive or negative predictive values among the tool, stand-alone hrHPV, and anal cytology with adjunct hrHPV. Sensitivity and specificity were not significantly different for stand-alone or adjunctive hrHPV testing. Compared with cytology, stand-alone hrHPV and the novel triage tool reduced unnecessary HRA referrals by 65% and 30%, respectively. Conclusions Stand-alone hrHPV would have missed 11 of 74 AIN2–3 and generated 74 fewer unnecessary HRAs than current cytology-based screening patterns, which led to 115 unnecessary HRAs in our cohort. We propose triaging those with low CD4 count, hrHPV positivity, and/or smoking history for HRA.

Predictive Value of an Alternative Strategy for Measuring Depth and Size of Stage 1 Vulvar Squamous Cell Carcinoma

Objectives Despite poor reproducibility for measuring vulvar cancer depth, 1-mm or greater invasion triggers lymphadenectomy for small tumors. Previous literature suggests that measuring depth from the nearest dysplastic rete peg (alternative method) rather than highest dermal papilla (conventional method) may be acceptable. Methods Pathologic staging and follow-up information were recorded for 100 pT1 vulvar squamous cell carcinoma (SCC) resected from 1990 to 2019. Conventional depth, alternative depth, gross/clinical size, and size of the invasive component were measured for each tumor. In this retrospective study, we evaluated which clinicopathologic factors were most predictive of lymph node involvement and recurrence. Results Depending on the measurements used (conventional vs alternative depth, clinical lesion size vs cumulative extent of invasive component), between 1 and 18 cases were downstaged to pT1a. All such cases were pN0, without lymphovascular or perineural invasion. Infiltrative cords (hazard ratio [HR] = 5.15; 95% CI = 1.63–16.2; p = .005) and perineural invasion (HR = 3.16; 1.18–8.45; p = .022) were most strongly associated with groin recurrence. Of staging criteria evaluated, only cumulative extent of the invasive component 2 cm or greater was significantly associated with groin recurrence (HR = 2.87; 1.01–8.17; p = .048). The Kaplan-Meier curves for local recurrence-free survival by stage did not show significant separation regardless of method. Conclusions Patients downstaged using alternative measurement techniques lacked nodal disease/recurrence; one-third of those with nodal sampling experienced postoperative morbidity. Our data suggest that the use of alternative depth and cumulative extent of invasion could safely allow some conventional stage IB vulvar SCC patients to avoid groin surgery, thereby reducing treatment-related morbidity.

Effects of Adherence to Colposcopy Guidelines on the Detection of Cervical Intraepithelial Neoplasia

Objectives Practice recommendations for the minimum steps to perform a colposcopy were published in 2017. The goals of this study are to assess whether adherence to these guidelines correlates with detection of cervical intraepithelial neoplasia and to analyze factors associated with rates of biopsy during colposcopy. Methods All colposcopies performed at 2 academic medical centers between 2018–2023 were identified by billing code. Patient demographics, cervical cancer screening, medical history, colposcopy details, and pathology were collected from retrospective medical record review. Adherence to guidelines was determined by the number of criteria met on colposcopy documentation. The outcomes assessed were grade of pathology and rate of biopsy. Results In univariable regression analysis, no association between adherence to guidelines and detection of cervical intraepithelial neoplasia 2+ was identified (odds ratio [OR] = 1.11, p = .12). When controlling for race, ethnicity, insurance type, Pap test cytology, and human papillomavirus vaccination status in multivariate analysis, there remained no statistically significant correlation (adj. OR = 1.11, p = .14). Black patients (OR = 0.66, p = .039), publicly insured patients (OR = 0.38, p < .001), and patients with HIV (OR = 0.39, p < .001) were each significantly less likely to have a biopsy taken during colposcopies compared to White, privately insured patients, or HIV-negative patients. In multivariate analysis, HIV and public insurance remained factors associated with lower rates of biopsy (adj. OR = 0.46, p < .001 and adj. OR = 0.63, p = .035, respectively). Conclusions The study found insufficient evidence to support current colposcopy guidelines. The analysis revealed disparities in the execution of biopsies during colposcopies, particularly in Black, publicly insured, and HIV-positive patients, underscoring the importance of standardization of colposcopic practices.

Feasibility and Acceptability of Human Papillomavirus Based Self-sampling in Underserved Minorities in the United States: A Scoping Review

Objective The aim of the review evaluates the feasibility and acceptability of human papillomavirus (HPV) self-sampling in underscreened communities to increase cervical cancer screening rates in the United States. Methods Database searches were conducted on PubMed, CINAHL, MEDLINE, CENTRAL, and ClinicalTrials.gov using the following search terms: HPV or human papillomavirus viruses, self-sampling, self-swabbing, or self-collection, acceptability, feasibility, and United States. The study aims to identify factors related to the feasibility and acceptability of HPV self-sampling uptake. Results Sixteen studies were included in this scoping review. Most studies reviewed associated factors, such as demographic data (age and ethnicity), and socioeconomic data (income, education level, and insurance status). There was a higher HPV self-sampling rate (75%–100%) in the 11 studies where there was an in-person component including completing self-sampling kits in-person after recruitment, scheduled appointments or education sessions compared with studies where kits were returned by mail (3%–93%). Eleven studies measured acceptability and/or feasibility, and subjects reported the self-sampling process and devices were acceptable and easy to use. Of the 11 that measured feasibility and acceptability, 3 studies noted that the majority preferred self-sampling over clinician-collected Pap tests. Six studies incorporated community health worker–led education prior to distributing self-sampling kits, and improved attitudes toward self-sampling. Two studies evaluated the incidence of abnormal results between self-sampling and clinician-collected Pap test and found no difference. Conclusions HPV self-sampling is seen as an acceptable and feasible option for cervical cancer screening for underscreened individuals. Furthermore, patient-facing education components led by community health workers greatly influenced participants' decision to self-sample.

Evaluating the Benefits of Endocervical Curettage in Women Infected With HPV16/18

Objective This study evaluates the effectiveness of endocervical curettage (ECC) in detecting additional high-grade squamous intraepithelial lesions or worse (HSIL+) in women infected with human papillomavirus (HPV) types 16 and 18, which may be missed by biopsy alone. Methods A retrospective cohort study analyzed the medical records of 4,811 women referred for colposcopy due to HPV16/18 infection from January 2019 to December 2023. Patients underwent both biopsy and ECC. Statistical comparisons of various clinical factors between HSIL+ and low-grade or normal lesions were performed using χ2 tests and logistic regression analyses, with stratified analysis to determine ECC's additional detection rate under different clinical conditions. Results Endocervical curettage detected an additional 6.46% of HSIL+ lesions missed by biopsy alone, with the highest rates in women with normal colposcopic impressions (23.1%), those aged 50 or older (12%), type 3 transformation zones (9.5%), and postmenopausal women (11.9%). In contrast, younger women under 30 and those with type 1 or 2 transformation zones had significantly lower detection rates (2.9%). Logistic regression indicated that older age, type 3 transformation zone, higher grade cytological results, and abnormal colposcopic impressions are significant risk factors for HSIL+ detection via ECC (p < .001). Conclusions Data from this study indicate that ECC would be beneficial for women over 30 with HPV16/18 infections, particularly those with type 3 transformation zones or normal colposcopy, as it enhances HSIL+ detection. However, it offers minimal benefit for younger women or those with type 1 or 2 transformation zones.

The Significance of Extended HPV Genotyping for Detecting Endocervical Glandular Neoplasia for Atypical Glandular Cells

Objectives This study aims to evaluate the risk of cervical glandular neoplasia with extended high-risk human papillomavirus (hrHPV) genotyping, in patients with atypical glandular cells (AGC) cytology. Methods Cervical AGC cases with concurrent extended HPV genotyping between October 2017 and October 2023 were retrieved from the archives of Department of Pathology, Obstetrics, and Gynecology Hospital of Fudan University (OGHFU). Results A total of 497 AGC cases with extended hrHPV genotyping showed an hrHPV-positive rate of 32.0%. The top 4 hrHPV types were HPV18, 16, 52, and 59. A total of 304 cases had histological follow-up. A total of 72 cases (23.7%) had cervical adenocarcinoma in situ/cervical intraepithelial neoplasia3 or worse (AIS/CIN3+) lesions with 43 endocervical carcinoma (EC-ADC), 28 AIS, and 1 CIN3. Cervical AIS/CIN3+ lesions were detected in 50.5% (55/109) of the hrHPV-positive group. Women with HPV18/16/45 positivity had 77.6% cumulative risk of cervical AIS/CIN3 + lesions (52/67), accounting for 94.6% (52/55) of the total hrHPV-associated cervical AIS/CIN3+ lesions. For all 15 other hrHPV types, the overall risk of AIS/CIN3+ was 7.1% (3/42 cases). The sensitivity, specificity, PPV, and NPV of the composite HPV18/16/45 group for detecting endocervical glandular neoplasia was 71.8%, 93.1%, 76.1%, and 91.6%, respectively. Endocervical carcinoma was found in 17 of 195 (8.7%) women with negative hrHPV testing, accounting for 39.5% EC-ADC (17/43) cases. Conclusions Atypical glandular cells was rarely related to CIN3. Atypical glandular cells was strongly related to AIS and EC-ADC. Women aged 30–49 years had highest risk for AIS/CIN3+ lesions. Although HPV test can be helpful, there were still some cases of HPV-negative endocervical adenocarcinomas. Extended HPV genotyping in AGC cases identified certain HPV types associated with a higher risk of cervical glandular lesions, potentially assisting with risk stratification.

Diagnosis to Excision: Estimates for Guideline-Concordant Treatment of High-Grade Cervical Intraepithelial Neoplasia

Objective To estimate the proportion of participants with high-grade cervical intraepithelial neoplasia (CIN 2/3) who completed indicated therapeutic procedures. Methods This was a retrospective observational cohort study of the National Institutes of Health's All of Us database enriched for racial and ethnic minorities historically underrepresented in biomedical research. The study included female participants aged 25 and older with a diagnosis of CIN 2/3 only, excluding invasive malignancy. The authors conducted both univariate and multivariate logistic regression to identify background characteristics associated with guideline-concordant ablative and excisional procedures. Results Of 1,764 participants with CIN 2/3, only 27.7% of participants underwent a therapeutic procedure in the 12 months following a diagnosis of CIN 2/3. The study found that Hispanic participants had a 1.48 increased odds ratio (OR) (95% CI = 1.18–1.85) of undergoing therapeutic procedures (compared to non-Hispanic). Participants residing in the Midwest had a 2.04 OR (95% CI = 1.6–2.6) of undergoing a therapeutic procedure compared to the Northeast. After adjustment for race, ethnicity, region, and smoking status, Hispanic ethnicity remained associated with therapeutic excision (OR = 2.37, 1.13–4.78). Geography was significant with 2.37 (95% CI = 1.17–3.29) increased odds of therapy completions for Midwest residents but 0.52 (95% CI = 0.27–0.96) decreased odds for Western residents. Conclusion In this large US national database enriched for racial and ethnic minorities, the authors found that 3 of 4 participants with cervical precancer did not undergo a therapeutic procedure in the 12 months following their first diagnosis. Increased efforts to promote access to and completion of treatment of CIN 2/3 are needed to prevent cancer.

Safety of LEEP in Treating CIN 2–3 During Pregnancy

Abstract Cervical intraepithelial neoplasia (CIN) 2–3, a premalignant lesion usually treated by Loop Electrosurgical Excision Procedure (LEEP) in nonpregnant women, is addressed differently in pregnant women. Data from 2006 to 2023 on 178 pregnant women with CIN 2–3 were provided by the Israeli Society of Colposcopy. Sixty-seven underwent LEEP within 15 weeks of gestation with only minor complications. Of the 57 continuing pregnancies, 53 (93%) delivered at term, 2 (3.5%) at 34–37 weeks, and 2 (3.5%) experienced missed abortions. One hundred eleven women were followed through pregnancy without LEEP. Of that group, 5 women were lost to follow-up. From 173 women on whom the authors have follow-up data, 9 (5.2%) were finally diagnosed with cervical cancer, 132 women (76.3%) remained CIN 2–3, and 32 women (18.5%) were CIN 1 or normal. Loop Electrosurgical Excision Procedure (LEEP) performed within the first 15 weeks of pregnancy in 67 women was safe. In 5.2% of pregnant women with CIN 2–3, the final diagnosis was invasive cancer.

Distribution and Severity of Cervical Intraepithelial Neoplasia in Women With Different Human Papillomavirus: An Analysis From Liaoning Province of Northeastern China

Objective Persistent infection with high-risk human papillomavirus (HPV) is a key contributor to cervical intraepithelial neoplasia (CIN), but the relation between high-risk HPV genotypes and the location of CIN lesions remains unclear. The aims of this study were to investigate the most frequent biopsy site of CIN lesions in women with different HPV infection and to analyze the biopsy times, CIN frequency, and the clustering of CIN frequency based on 12-o'clock sites and cervical quadrant locations. Materials and Method We conducted a retrospective study of HPV detection and genotyping at the virology department of our hospital. Colposcopy exams were performed by specialists according to a standardized protocol, and all visually abnormal areas were further biopsied. Pearson chi-squared tests and cluster analyses were implemented to analyze the data. Results Among 1,381 women enrolled in this study, 933 cases infected with HPV. HPV16, HPV58, and HPV18 were the most common genotypes. The most frequent biopsy site was the 6 o'clock position. The highest frequency of high-grade CIN findings in single-genotype HPV groups was the 6 o'clock position and that for multiple-genotype HPV group was the 12 o'clock location. All CIN clusters were found in the 6 and 12 o'clock biopsy sites, except in the HPV18 group. Quadrant 2 and 4 were clustered in most groups. Conclusions The 6 and 12 o'clock sites in cervical quadrant 2 and 4 should be targeted during cervical biopsy procedures. These findings can provide clinicians with specific recommendations on the optimal site for CIN biopsy when considering the HPV genotype.

Vulvar Inspection During Cervical Cancer Screening Procedures: The Ugly Reality

Abstract Vulvar examination during procedures for cervical carcinoma screening (CCS) can be a valid chance for early diagnosis of vulvar diseases and precancerous lesions. With this aim an online questionnaire was sent to the members of the Italian Cervical Carcinoma Screening Group (GISCi) from either first level group (FLG, Pap/human papillomavirus test sampling) or second level group (SLG, colposcopy and treatments) to assess if and how vulvar examination was performed. 86% of FLG and 90.2% of SLG report performing vulvar examination prior to CCS procedures. 15% of SLG cannot manage basic vulvar diseases and they refer patients to specialized center. 54.3% underline lack of standardized protocol in case of vulvar disease detection. Despite most health care professionals report examining the vulva during CCS procedures, vulvar cancer early diagnosis is still challenging.

Management of Malignant Vulval Melanoma: A Retrospective Case Series and Review of the Literature

Objectives The aims of the study were to evaluate clinicopathologic features, management, and outcomes in vulval melanoma and to review the literature. Materials and Methods Data were collected retrospectively on patients with vulval melanoma from 2001 to 2017 in 5 gynecological oncology cancer centers (Bristol, Taunton, Truro, Plymouth, and Cheltenham). SPSS software was used for univariate and multivariate statistical analysis. Disease-specific median survival was calculated using Kaplan-Meier curves. Results Forty-four patients with vulval melanoma were included, with a median age of 71 years. Forty-three of 44 had wide local excision with full inguinal lymphadenectomy if abnormal lymph nodes. Seven patients had sentinel lymph nodes. However, 2 patients with negative sentinel lymph nodes had distant recurrences within 16 months. On univariate analysis, presence of ulceration (p = .012), perineural invasion (p = .03), and area of lesion (p = .016) were associated with risk of recurrence but only presence of microsatellites (p = .01) was associated with risk of death. There were 31 deaths (70%): 29 (94%) of 31 from melanoma and 28 (64%) of 44 recurrences: 17 local (10 groin, 7 vulval) and 9 distant. Overall median survival was 32.5 months (95% CI, 17.8–46.5 months) and median recurrence-free survival 12.6 months (95% CI, 7.7–17.4 months). Conclusions This retrospective multicenter study highlights the high recurrence rate and poor prognosis of vulval melanoma. Lymph node surgery did not make any difference to recurrence-free survival or overall survival. The presence of microsatellites was associated with a statistically increased risk of death.

Time Differences From Abnormal Cervical Cancer Screening to Colposcopy Between Insurance Statuses

Objective Screening and diagnostic follow-up to prevent cervical cancer are influenced by socioeconomic and systemic factors. This study sought to characterize intervals from abnormal cervical cancer screening to colposcopy between practices differing by insurance status at a large, urban academic center. Materials and Methods This retrospective cohort study included patients aged 21–65 who presented for colposcopy between January 1, 2021, and January 1, 2022, at the resident and faculty gynecology practices of a single large urban academic medical center. Patient characteristics were compared using t tests or Wilcoxon rank sum tests for continuous measures and χ2 or Fisher exact tests for categorical measures. Intervals from abnormal cervical cancer screening to colposcopy were compared using the Wilcoxon rank sum test and linear regression analysis with multivariable models adjusted for age, cervical cytology result, human papillomavirus result, and HIV status. Results Resident practice patients were publicly insured and more likely to be Black or Hispanic (p < .0001); rates of high-risk human papillomavirus and smoking were similar. Resident practice patients had longer intervals from abnormal cervical cancer screening to colposcopy compared with faculty practice patients (median 79.5 vs 34 d, p < .0001). On adjusted analysis, resident practice patients faced a 95% longer interval (p < .0001). Conclusions Publicly insured patients of a resident-based practice faced significantly longer intervals from abnormal cervical cancer screening to colposcopy than faculty practice patients at a single urban academic center. Effort to address these differences may be an area of focus in improving health disparities.

The Incidence of Cervical Intraepithelial Neoplasia or Cervical Cancer in Women Referred With Postcoital Bleeding

Objectives The incidence of cervical cancer among patients with postcoital bleeding (PCB) was the primary objective of this study. Furthermore, the proportion of cervical intraepithelial neoplasia requiring treatment and the correlation between PCB and the presence of high-risk human papillomavirus (HPV) was determined. Lastly, the study aimed to identify risk factors among the referred women. Methods A retrospective cohort study was conducted at a university hospital in Denmark between January 1, 2017 and December 31, 2019. Women referred with PCB were identified with the ICD diagnosis codes “DN930 Postcoital and contact bleeding” and “DN930B Contact bleeding.” Demographic and paraclinical data were extracted from the journals and the supportive systems: Patoweb and the Danish Microbiology Database. Results A total of 789 women were included in this study, with only 0.25% (n = 2) diagnosed with cervical cancer and 2.5% (n = 20) diagnosed with cervical intraepithelial neoplasia II–III and adenocarcinoma in situ. Human papillomavirus testing was only conducted in a minority of cases, and a low incidence of high-risk human papilloma virus was detected in the 22 cases, n = 5. Conclusions A very low incidence of cervical cancer and high-grade cervical intraepithelial neoplasia reported among women referred with PCB. Prognostic factors as body mass index, smoking, and HPV vaccination status may predict the risk of cervical cancer. Selection criteria like primary testing for hrHPV and cytology as cotests before referral to colposcopy may reduce the number of unnecessary colposcopies.

Awareness Level of Cervical Cancer Patients Referred to Radiation Oncology Outpatient Clinics—A Multicenter Study

Objective The study aimed to assess the level of knowledge of patients with cervical cancer referred to radiation oncology outpatient clinics in Turkey regarding screening methods and human papillomavirus (HPV) vaccination and increase social awareness based on the findings. Methods A descriptive cross-sectional survey was conducted from January to June 2022 involving 300 patients in various regions. Data on demographics, cervical cancer screening and HPV vaccination knowledge, and recommendations to relatives were collected through a questionnaire-based interview. Univariate logistic regression analyzed the impact of independent variables on knowledge levels. Results Among the participants, 57% were unaware of cervical cancer screening, and 66% had no knowledge of the HPV vaccine. Higher knowledge levels were associated with higher education, older age at marriage and first birth, and previous gynecological checkups. Lower knowledge levels were observed in patients treated at state institutions, with no formal education, and diagnosed with cervical cancer at age 60 or older. A significant inverse correlation was found between knowledge levels and the stage of cancer at diagnosis, with higher awareness in earlier stages. Conclusion The study revealed limited awareness among cervical cancer patients in Turkey regarding screening and HPV vaccination. Lower knowledge levels were associated with specific demographic factors, emphasizing the importance of targeted educational campaigns to reduce the burden of cervical cancer and promote early detection. Efforts to enhance vaccination coverage and encourage early screening can significantly improve outcomes. Comprehensive awareness surveys are essential in guiding policymaking and implementing effective early detection and prevention strategies for cervical cancer.

Performance of Different Follow-Up Strategies and Genotype-Based Recurrence Risk After Treatment of Cervical High-Grade Squamous Intraepithelial Lesion

Objective Our aim was to evaluate the performance of different follow-up strategies after treatment for cervical intraepithelial neoplasia (CIN) 2 or 3, including human papillomavirus (HPV) detection, cytology, or colposcopy, as well as their combinations. Additionally, we compared the influence of the persistence of HPV 16/18 versus that of other high-risk HPV genotypes (HR-HPV) in the recurrence risk. Methods Retrospective register-based study, including women who had an excision of the transformation zone for CIN2 or CIN3 at our institution, between January 2011 and December 2022. The outcome assessed was histopathological recurrence/persistence of CIN2 or worse. Results Of the 721 women included, 6.8% (49/721) had recurrence/persistence. The sensitivity, specificity, and positive and negative predictive values of the HPV test were 97.4%, 80%, 22.3%, and 99.8%, respectively, whereas for cotesting (HR-HPV and cytology), 86.8%, 90.1%, 34.4%, and 99.1%, respectively. The referral rates for colposcopy were 24.3% and 14.2%, respectively. The sensitivity of colposcopy was low (40.0%). Women who were initially positive for non-16/18 genotypes at baseline who became HPV16/18 positive during follow-up, had a statistically significant increased risk of CIN2 or worse, compared with those who tested positive only for other HR-HPV genotypes during both stages (hazard ratio = 4.98; 95% CI = 1.66–14.91). Conclusions Human papillomavirus testing is the best strategy for follow-up after treatment of cervical HSIL. The addition of cytology triage decreases by more than 40% the referrals for colposcopy, without significantly missing cases of recurrence/persistence. Human papillomavirus 16/18 in the follow-up, regardless of being previously positive, is associated with higher risk of recurrence/persistence of HSIL.

Adenocarcinoma In Situ of the Uterine Cervix (AIS) Treated by Loop Electrosurgical Excision Procedure Strategy: An Observational Study

Objectives Evaluation of the results of treatment of adenocarcinoma in situ by loop electrosurgical excision procedure and the safety of a conservative strategy. Methods Identification of all cases of adenocarcinoma in situ treated by loop electrosurgical excision procedure at our institution and follow-up by a conservative strategy. Completeness of the identification of all cases was secured by data from the National Pathology Registry. The treatment strategy was based on cytologic follow-up performed by a general practitioner and, irrespective of margin status of the cone, only the results of the postoperative surveillance were indicative of further treatment. Results A total of 224 patients were identified. The overall recurrence rate with a mean follow-up time of 87.8 months was 7.6% (17/224). The recurrence rate in patients with involved margins was significantly higher than in patients with uninvolved margins, 15.7% vs 5.2%, respectively. Six recurrences were diagnosed at first examination 6 months postconization in patients with involved margins. They were treated with hysterectomy in 4 cases and reconization in 1 case. If involvement of margins alone had been an indication of further therapy (hysterectomy or reconization) immediately after conization, the conservative management strategy prevented 46 surgical procedures. Two cases of invasive cancer were diagnosed during follow-up, 150 months and 196 months after primary treatment, and after normal follow-up examinations. These 2 cases must be considered de novo cases and cannot be considered treatment failures. Conclusion The conservative management strategy thus seems safe, and unnecessary surgical procedures were avoided.

Women 50 Years and Older With Negative Pap Test and Positive Human Papillomavirus Test for Genotypes Other Than 16 and 18—Follow-up Outcomes

Objective A follow-up of women 50 years or older with concomitant positive high-risk human papillomavirus (HPV) genotypes other than 16 and 18 (hrHPVO) and negative Pap test (NILMPap) was conducted to better understand the implications of hrHPVO positivity on potential risk of developing significant high-grade lesions. Material and Methods A retrospective review of 2014 cytology data of patients with co-testing (Pap test and HPV DNA) identified 85 women 50 years or older with NILMPap and hrHPVO+. Results Most patients (63) had repeat co-testing on next follow-up. Of these, 41 patients with persistent hrHPVO+ status, 3 developed cervical intraepithelial neoplasia 2 (CIN2), and 1 CIN3. Nineteen patients were followed with biopsies. Of these, 7 biopsies were abnormal, 5 of which showed low-grade (CIN1) and 2 high-grade (CIN3) histology; none progressed on further follow-up. Three patients were followed with Pap test only, all had NILMPap, and none progressed on further follow-up. In summary, of the 85 patients, 26 developed abnormal histology during follow-up, 6 of whom had high-grade histology (CIN2 and CIN3, 3 each). The 5-year risk of CIN1+ in this cohort was 43.8% and for CIN2+ was 12.3%. The risk of abnormal histology did not differ significantly by prior history of Pap tests, histology, and/or HPV results. Conclusions A persistent positivity for hrHPVO indicated higher likelihood to develop a lesion, and this risk was not reduced for patients 50 and older compared with the published screening population risk.

Unusual Presentation of Lymphangioma Circumscriptum of the Vulva: In Association With Crohn Disease

Abstract Lymphangioma circumscriptum (LC) is a rare benign condition, with marked dilation of surface lymphatic vessels in the deep and subcutaneous layers. Vulvar LC can become a highly disabling condition with vulvar discomfort, itching, burning and lymph seeping being the dominant symptoms. Biopsy is mandatory for the diagnosis. There is no consensus on the standard treatment for vulvar LC and recurrence is frequent. In complex cases with wide disease location, combination of different treatment options, such as abrasive methods and surgery, may lead to the best clinical and aesthetical result, with extended disease-free periods. We present a patient with a long history of Crohn disease with multiple pelvic surgeries who developed an extensive vulvar LC.

Colposcopy—A Valuable Diagnostic Tool for Pregnant Women With Unexplained Vaginal Bleeding

Objectives We aimed to examine the diagnostic value of colposcopy in a large cohort of pregnant women with unexplained vaginal bleeding during the second or third trimester. Materials and Methods This retrospective study included women who underwent colposcopy due to vaginal bleeding in the second and third trimesters during 2012–2022 at a tertiary care hospital. Demographics, obstetric data, bleeding characteristics, colposcopy results, cervical cytology testing, a sonogram directed at the placenta, and birth details were collected. Results In total, 364 women were included. The mean maternal age was 29.7 years and the mean gestational age at examination was 30.7 weeks. Vaginal bleeding was mild in 80.8%, moderate in 14.6%, and severe in 4.7%. Only 3.3% had been vaccinated against human papilloma virus and 25.5% underwent a Pap smear study before pregnancy. Colposcopy diagnosed the bleeding source in 83 women (22.8%). The colposcopic examination revealed vaginal bleeding due to contact bleeding from ectropion in 46 (12.6%), a decidual/cervical polyp in 37 (10.2%), acetowhite epithelium in 12 (3.3%), herpes genetalis in 2 (0.5%), and bleeding from vaginal varices in 2 (0.5%). Of those who were recommended a follow-up examination after the postpartum period, only 49.1% completed such. Among women with compared to without postcoital bleeding (N = 72), the risk of abnormal colposcopic findings was higher (24 [33.3%] vs 54 [19.7%], p = .017) and the rate of abnormal Pap smear was higher (7 [13.2%] vs 7 [3.2%], p = .008). Conclusions Colposcopy can be a valuable diagnostic tool for women with unexplained vaginal bleeding in the second or third trimester.

Attitudes About the Human Papillomavirus Vaccine Among Patients With and Without Cervical Dysplasia

Objectives The aims of the study are to examine the perception of the human papillomavirus (HPV) vaccine among those with and without a history of cervical dysplasia and to examine perceptions of the vaccine for their children. Materials and Methods Patients were recruited to complete a survey about the HPV vaccine for both themselves and their children. Patients in a colposcopy clinic with a history of abnormal cervical cytology and patients in a benign gynecology clinic without a history of abnormal cervical cytology were recruited. Participants' medical records were reviewed. Demographics and survey answers were described, and Fisher exact test was used to compare the groups. Results One hundred eighty-three patients participated: 73 in colposcopy clinic and 110 in benign clinic. The majority self-identified as Black (74% colposcopy, 71% benign, p = .588) and reported an income less than $39,000 a year (77% colposcopy, 65% benign, p = .089). Fifty-six percent in benign clinic agreed the HPV vaccine is a good way to protect oneself from disease compared with 48% in colposcopy clinic (p = .022). When examining results based on cytology, fewer patients in the highest-grade cytology group agreed the vaccine was effective (30% high-grade, 48% normal, 57% low-grade, p = .027) or a good way to protect themselves from disease (29% high-grade, 53% normal, 62% low-grade, p = .002). There was otherwise no statistically significant difference between the groups on questions regarding self or child vaccination. Conclusions In a majority Black, low-income population, patients without a history of abnormal cervical cytology have more favorable perceptions of the HPV vaccine's effectiveness in preventing disease. Those with the highest-grade cytology had more negative perceptions of the vaccine's effectiveness and protectability.

Psychological Distress in Women With Abnormal Pap Smear Results Attending Cervical Cancer Screening

Objective Women often experience psychological distress upon receipt of an abnormal Pap test result. This study aimed to evaluate psychological distress and its correlates among women who received an abnormal Pap screening test result. Material and Methods A cross-sectional study was performed in a cohort of 172 consecutive women who had attended screening for cervical cancer and who received abnormal Pap smear results and underwent additional diagnostic procedures (colposcopy/biopsy/endocervical curettage). The participants filled out a questionnaire on sociodemographic variables and the Cervical Dysplasia Distress Questionnaire. Multivariate linear regression was used for the analysis of the data. For multiple comparisons, the Bonferroni correction was applied to adjust the level of significance. Results In women who received an abnormal Pap smear result, the independent correlate of higher psychological distress (by Cervical Dysplasia Distress Questionnaire score) before diagnostic procedures was lower satisfaction with information/support received from other people (p = .002). Correlates of psychological distress in women older than 40 years with abnormal Pap smear were anxiety (p = .042) and worry about having cervical cancer, general health and having sex (p = .044). Conclusions The authors’ findings could enable control of factors predictive of psychological distress in women who received a positive Pap smear screening test before undergoing diagnostic procedures, primarily via active provision of targeted information.

Opportunities Missed: Cervix Cancer Screening Failures in Women Aged 65 and Older

Objectives This study aimed to determine the screening history and associated outcomes of women diagnosed with cervical cancer after age 65. Methods All patients from 2012 to 2021 diagnosed with squamous, adenocarcinoma, neuroendocrine, or adenosquamous cervical cancer after age 65 in a single managed care organization (MCO) were included in this retrospective cohort study. Demographic, medical, screening, pathologic, follow-up, and treatment data were extracted. Statistical analysis was done using chi-square test and logistic regression. Cancer-specific survival was estimated using the Kaplan-Meier method. Results Of 2,175 patients screened, 209 met inclusion criteria. Only 26.3% of patients had appropriate cervical cancer screening and 41% of patients died of their disease. Managed care organization membership duration of more than 5 years positively correlated with proper cervical cancer screening (p < .001); however, 64% of the long-term members still did not meet criteria to end screening at age 65, with 42.6% of these patients having more than 25 physician visit opportunities to address screening. Increased physician visits correlated with earlier stage at diagnosis of cervical cancer (p = .012). Median cancer-specific survival was significantly better in properly screened patients at 68 vs 30 months, respectively (p = .03). Conclusions Most patients diagnosed with cervical cancer after age 65 did not have adequate previous screening, including those who were MCO members for more than 5 years. There were many missed opportunities for screening, despite multiple provider touchpoints. The authors’ data suggest that adequate screening confers a survival benefit secondary to earlier stage at diagnosis. Further study in this age group is needed to redefine the criteria to end cervix cancer screening.

Enduring Consensus Guidelines for Cervical Cancer Screening and Management: Introduction to the Scope and Process

Objectives The Enduring Consensus Cervical Cancer Screening and Management Guidelines (Enduring Guidelines) effort is a standing committee to continuously evaluate new technologies and approaches to cervical cancer screening, management, and surveillance. Methods and Results The Enduring Guidelines process will selectively incorporate new technologies and approaches with adequate supportive data to more effectively improve cancer prevention for high-risk individuals and decrease unnecessary procedures in low-risk individuals. This manuscript describes the structure, process, and methods of the Enduring Guidelines effort. Using systematic literature reviews and primary data sources, risk of precancer will be estimated and recommendations will be made based on risk estimates in the context of established risk-based clinical action thresholds. The Enduring Guidelines process will consider health equity and health disparities by assuring inclusion of diverse populations in the evidence review and risk assessment and by developing recommendations that provide a choice of well-validated strategies that can be adapted to different settings. Conclusions The Enduring Guidelines process will allow updating existing cervical cancer screening and management guidelines rapidly when new technologies are approved or new scientific evidence becomes available.

Does the New National Cervical Screening Programme Guideline Detect Cases of High-Grade Squamous Intraepithelial Lesions That Previously Would Have Been Missed?

Objective The aim of this study was to determine the number of patients undergoing large loop excision of the transformation zone (LLETZ), for biopsy-confirmed high-grade squamous intraepithelial lesions (HSIL), where the original cervical screening test (CST) reported oncogenic human papillomavirus (HPV) and negative liquid-based cytology (LBC). This reflects the number of patients where a LLETZ procedure would not have occurred under the previous guideline. Methods Retrospective observational chart review of all patients (n = 477) who underwent LLETZ procedure in a single tertiary unit over a 36-month period. Prevalence of negative histopathology, positive margins, incidental cervical cancer, and accuracy of HSIL identification at colposcopy were measured. Diagnostic accuracy of HSIL diagnosis from initial colposcopic impression was calculated; factors influencing accuracy were evaluated using multivariable logistic regression analysis. There were no comparators. Results Of 477 LLETZs, 5.9% (n = 28) were for oncogenic HPV and normal LBC on referral CST. Demographics between the “study” (oncogenic HPV and normal LBC on referral CST) and the “standard” group were similar, except the study group was less likely to be using contraception (25% vs 47%, p = .023). In the study group, initial colposcopic cervical biopsy confirmed HSIL in 91.6% (n = 27) and low-grade squamous intraepithelial lesions in 3.6% (n = 1). Histopathological analysis of LLETZ specimens confirmed HSIL in 20 patients (71.4%) and low-grade squamous intraepithelial lesions in 2 (7.1%). No microinvasion was detected. Conclusions The renewed National Cervical Screening Programme (NCSP), is detecting more “at risk” patients, predicted to lead to a further reduction in incidence of cervical cancer in adequately screened patients.

Recurrent High-Grade Squamous Intraepithelial Lesion After Loop Excision Procedure Versus Loop Procedure With Top Hat

Objective To evaluate single-pass loop electrosurgical excision procedure (LEEP-SP) versus LEEP with top hat (LEEP-TH) in terms of treatment failure defined as high-grade squamous intraepithelial lesion (HSIL) cytology within 2 years’ follow-up. Methods This single-institution cohort study used a prospectively collected cervical dysplasia database including all patients who underwent LEEP-SP or LEEP-TH for biopsy-proven cervical intraepithelial neoplasia between 2005 and 2019. Results Of 340 patients included, 178 underwent LEEP-SP and 162 LEEP-TH. The LEEP-TH patients were more likely to be older (mean age, 40.4 vs 36.5 years; p < .001) and have a positive preprocedure endocervical sampling (68.5% vs 11.8%; p < .001). Positive margins were found in 23 LEEP-SP (12.9%) and in 25 LEEP-TH (15.4%; p = .507). There was no significant difference in depth of excision between LEEP-SP (13.21 ± 23.19 mm) and LEEP-TH (17.37 ± 28.26 mm; p = .138). At 2 years, there was no difference in the rates of HSIL cytology (5.2% vs 6.3%; p = .698), any positive human papillomavirus test, or HSIL cytology (25% vs 15%; p = .284). The 57 patients undergoing repeat excision were more likely to be older (mean age, 40.95 vs 37.52 years; p = .023), have had a LEEP-TH (26.3% vs 73.7%; p < .001), and have initial cytologic HSIL (64.9% vs 35.0%; p < .001). Conclusions In this single-institution study, there is no difference in the rate of recurrent HSIL in patients undergoing LEEP-SP versus LEEP-TH. A LEEP-TH may have limited additional benefit over a LEEP-SP in the treatment of cervical HSIL.

Comorbid Vulvar Lichen Sclerosus and High-Grade Squamous Intraepithelial Lesions: A Management Conundrum

Objective This study aimed to determine if treating lichen sclerosus (LS) with high-potency topical corticosteroids (TCS) increases the risk of high-grade squamous intraepithelial lesion (HSIL) recurrence in patients with comorbid vulvar LS and HSIL. Methods This is a retrospective study of patients with comorbid vulvar LS and HSIL treated with TCS between 2015 and 2020. Patients with clinically diagnosed or biopsy-proven LS and biopsy-proven HSIL of the vulva were included. Clinical data included demographics, tobacco use, immune-modifying conditions, specimen pathology, treatment types, and HSIL recurrence. Bivariate analysis was performed to compare demographic and clinical characteristics between patients with and without HSIL recurrence. Results Twenty-six patients with comorbid LS and HSIL were identified. The median age was 66.0 years and median time in treatment for LS was 5.5 years. Thirteen (50%) had recurrence of HSIL and 13 (50%) did not have recurrence. Exposure to high-potency TCS was present in 20 (77%) patients, with 17 (65%) having use of more than 1-year duration and 9 (35%) having use at the time of HSIL diagnosis. When comparing the groups with and without HSIL recurrence, there was no significant difference in high-potency TCS exposure, duration of use, or use at time of HSIL diagnosis. Conclusions High-potency TCS use for the treatment of LS did not seem to increase the risk of HSIL recurrence in patients with comorbid vulvar LS and HSIL. This suggests that high-potency TCS can be appropriately used for the treatment of LS even when HPV-associated disease is present.

Risk Factors for Positive Margins in High-Grade Cervical Intraepithelial Neoplasia After Transformation Zone Excision

Objective The aim of the study was to evaluate risk factors for positive margins on surgical specimens of patients submitted to transformation zone excision (TZE). Materials and Methods We conducted a retrospective study evaluating women submitted to TZE in our center, between 2012 and 2020. Our study population included only women with the diagnosis of high-grade intraepithelial lesion (HSIL) in the pathologic examination of the TZE surgical specimen. Positive margins were defined as the presence of HSIL in the endocervical and/or ectocervical margin of the specimen. Factors evaluated included demographic characteristics, pretreatment Pap smear and human papillomavirus test, colposcopic findings, TZE indication, and pathologic features of the surgical specimen. We performed univariate analysis and logistic regression modeling including variables associated with the outcome of positive margins in the univariate analysis. Results Our sample included 264 women, with a 15.2% positive margins rate (40 patients). In the univariate analysis, patients with immunocompromised status, HSIL Pap smear, and higher number of quadrants involved in colposcopic examination were more likely to have positive margins. After multivariate analysis, only immunocompromised status was found to be an independent risk factor (odds ratio = 4.94; 95% CI = 1.43–17.15; p < .05). Conclusions Immunocompromised status was the sole significant predictor for positive margins in TZE surgical specimens. To our knowledge, this is the first report of immunodepression as a risk factor for positive margins in cervical excisional procedures.

The Incidence of Vaginal Intraepithelial Neoplasia 2+ in Patients With Previous Hysterectomy Cervival Intraepithelial Neoplasia 3+ Between 2005–2015: A Population-Based Study

Objectives In light of the rarity of vaginal cancer, the role of vaginal vault testing following hysterectomy for preinvasive or early cervical cancers is unclear. The objective was to determine the subsequent risk of VaIN2/3, and invasive vaginal cancer following hysterectomy, and to potentially identify individuals at higher risk who may benefit from vaginal vault testing. Methods The authors performed a population-based retrospective study using administrative databases to identify the study population. They identified patients who between 2005–2015 underwent hysterectomy after cervival intraepithelial neoplasia 3+ (CIN3+)/adenocarcinoma in situ (AIS) and calculated the rate of VAIN2 and invasive vaginal cancer. Exclusion criteria are as follows: <21 years and CIN3+ diagnosis prior to 2005. Patients were followed until 2021. Results During the study period, 6,230 patients underwent hysterectomy for a diagnosis of CIN3+/AIS. The subsequent rates of VaIN2/3, in situ, and invasive cancer were 1.9% (119/6,230) and 0.3 (18/6,230), respectively. Of these, most (84.7%) were made within 5 years of hysterectomy and remained stable over time (2.0% in 2005–2009, 2.4% in 2010–2015). However, only 54% of patients had vault cytology after hysterectomy; among these, 8.2% were abnormal of which 22.8% were diagnosed with VAIN2+. In addition, the risk of VaIN2+ was 5.8% when there was residual CIN3+ versus 2.1% when absent. Conclusions Individuals with evidence of CIN3+/AIS at time of hysterectomy are at elevated risk of developing VAIN 2+, with the highest risk occurring within 5 years from surgery. Vault cytology within 1 year of surgery will identify most cases of VAIN2+, but further data monitoring and integration of HPV testing will be required to determine this screening strategy.

The International Society for the Study of Vulvovaginal Disease Surgical Oncological Procedure Definitions Committee “Surgical Terminology for Vulvar Cancer Treatment”

Objectives The International Society for the Study of Vulvovaginal Disease (ISSVD) Surgical Oncological Procedure Definitions Committee propose a consistent terminology based on well-defined and reproducible anatomic landmarks that can be used by all who are involved in care of patients with vulvar conditions. Materials and Methods The fundamental principles behind the new terminology contained descriptions of the area extension and depth of the surgical procedure. Results Vulvar Surgical Topographic Anatomy Landmarks Extension. The internal border of the vulva is the hymenal ring. The genitocrural folds are the external lateral borders. The vertical line through the clitoris and the anus defines lateral portions of the vulva. The horizontal line from the upper border of the hymenal ring defines anterior and posterior portion of the vulva. Depth. The floor of the vulva is represented by the median perineal fascia or perineal membrane of the urogenital diaphragm. A. Vulvectomy 1. Extension: partial/total vulvectomy. Removal of part/entire vulvar/perineal integument independent of the depth. 2. Depth: superficial/deep. Removal of the most superficial layer/removal of the vulvar tissue to the superficial aponeurosis of the urogenital diaphragm and/or pubic periosteum. B. Inguinofemoral lymphadenectomy 1. Superficial inguinofemoral lymphadenectomy. Removal of the nodes located beside the inguinal ligament and along the great saphenous vein. 2. Deep femoral lymphadenectomy. Removal of the nodes below the cribriform lamina and medial to the femoral vein. Conclusions This terminology helps avoid confusion and promote better understanding and exchange of experiences among gynecologic oncologists involved in vulvar carcinoma care.

A Case of Basaloid Differentiated Vulvar Intraepithelial Neoplasia

Steroid Phobia in Patients With Vulvar Lichen Sclerosus

Objective Steroid phobia in people with dermatologic conditions is associated with noncompliance with topical corticosteroids (TCS). Although it has not been studied in those with vulvar lichen sclerosus (vLS), first-line therapy is lifelong maintenance TCS, and noncompliance is associated with impaired quality of life, progression of architecture changes, and vulvar skin cancer. The authors aimed to measure steroid phobia in patients with vLS and determine their most valued sources of information to direct future interventions to address this phenomenon. Methods The authors adapted a preexisting, validated scale for steroid phobia (TOPICOP), which is a 12-item questionnaire that produces a score of 0 = no phobia and 100 = maximum phobia. The anonymous survey was distributed across social media platforms with an in-person component at the authors’ institution. Eligible participants included those with clinical or biopsy-proven LS. Participants were excluded if they did not consent or did not communicate in English. Results The authors obtained 865 online responses over a 1-week period. The in-person pilot obtained 31 responses, with a response rate of 79.5%. Mean global steroid phobia score was 43.02 (21.9)% and in-person responses were not significantly different (40.94 [16.03]%, p = .59). Approximately 40% endorsed waiting as long as they can before using TCS and stop as soon as possible. The most influential sources to improve patient comfort with TCS were physician and pharmacist reassurance over online resources. Conclusions Steroid phobia is common in patients with vLS. Focused efforts to address steroid phobia among health care providers is the next best step toward improving patient comfort with TCS.

Erosive Vulvar Lichen Planus and Risk of Vulvar Neoplasia

Objective The aim of the study was to assess the risk of vulvar cancer and precursors in a cohort of women with vulvar lichen planus (LP) and the clinical and therapeutic features of these patients. Materials and Methods A retrospective cohort study, including all the women with the diagnosis of vulvar LP, followed in one institution during a period of 11 years, was performed. Demographic and clinical data, as well as treatment, follow-up, and histology results, were evaluated. Results A total of 127 women were diagnosed with vulvar LP. The mean follow-up time was 3.9 ± 0.5 years (range = 1–11 years). Ultrapotent topical corticosteroids were first-line treatment in 91.8% (n = 112), with 32 cases (25.2%) needing an alternative treatment. Overall, 30 biopsies were performed in 19 women (15%). Vulvar high-grade squamous intraepithelial lesion was diagnosed in 3 women (2.4%), 2 (1.6%) of whom were later diagnosed with vulvar squamous cell carcinoma. No cases of differentiated vulvar intraepithelial neoplasia were observed. Conclusions Premalignant/malignant transformation in women with vulvar LP under surveillance and compliant with treatment is low. A close follow-up seems to be crucial to prevent future malignancy. Biopsies should be performed whenever a suspicious lesion seems during follow-up.

Clinical Challenges in Managing Cervical Intraepithelial Neoplasia 2: A Report From a Cross-sectional Survey

Objectives The aims of the study were to determine the management strategies offered to women with cervical intraepithelial neoplasia 2 (CIN 2) and the attitude of colposcopists toward its histological diagnosis and to identify the criteria used to select women for conservative management. Methods Colposcopists working in Spain were invited to participate in an online questionnaire via the Spanish Gynecology and Colposcopy Societies. The survey included 42 questions covering the 3 objectives of the study. One hundred eighty-two colposcopists representing all autonomous regions in Spain responded. The response rate was 26.2%, considering the total number of members. Results Most colposcopists offer conservative management in selected cases (153/182). The preferred follow-up interval is 6 months (65%), followed by 3–4 months (30%). Observation was considered no longer appropriate after 24 months (29.5%) and 12 months (26.3%), and 24.3% expressed that it depended on women's plan to conceive. During conservative management, 93.9% always perform a cytology, 62.7% human papillomavirus testing, 96.8% colposcopy, 47.9% cervical biopsy, and 28.1% endocervical curettage. Forty-five percent consider that CIN 2 merely represents a misclassified CIN 1 or CIN 3, whereas 46.2% think that CIN 2 lesions are unlikely to regress. Most respondents considered that age older than 40 years (81.3%), human papillomavirus 16 infection (62.1%), HIV infection (76.8%), positive p16 immunostaining (60.2%), a large lesion occupying more than 50% of the cervix (87%), endocervical involvement (91.6%), and previous treatment for CIN 2–3 (77%) are contraindications for conservative management. Conclusions Management of CIN 2 remains challenging for colposcopists, and a lack of consensus still exists in clinical practice. A better understanding of the natural history of CIN 2 and its clinical outcomes is still necessary to guide clinicians in its management.

Thermal Ablation of High-Grade Premalignant Disease of the Cervix—Standing the Test of Time: A Retrospective Study

Objective Analyze long-term (20 years) cytology and histology outcomes after treatment of high-grade cervical intraepithelial neoplasia (HGCIN) with thermal ablation (TA). Methods All women having TA for HGCIN between January 1996 and December 1998 (36 months; N = 885) were identified; data were collected on age of patients, symptoms, colposcopy findings, and biopsy reports. Local and national (cytology and colposcopy) databases and colposcopy records were used to collect long-term follow-up data. Probability of CIN recurrence was assessed using Kaplan-Meier “survival” curve. Results Follow-up data (available for 796) was collected in 2018 capturing 20 years of follow-up data. Two hundred eighty-one women were treated for CIN 2 and 515 women for CIN 3. Seven hundred ninety-one of 796 (>99%) were treated at first visit. Two hundred sixty two of 796 (33%) had evidence of crypt involvement on pretreatment biopsy. Probability of having consistently normal cytological follow-up was 92%, 89%, 86%, and 83% at 5, 10, 15, and 20 years, respectively. Cumulative probability of having recurrent HGCIN was 0.5% at 5 years, 1% at 10 years, 1.9% at 15 years, and 3% at 18 years. There was 1 invasive squamous cell cancer at 11 years after treatment. Conclusions Thermal ablation is a safe and effective treatment for HGCIN, which is now shown to have stood the test of time. We advise more widespread adoption in the United Kingdom and globally so long as agreed criteria are met.

Human Papillomavirus Genotype Attribution and Integration in High-Grade Vaginal Intraepithelial Neoplasia

Objective The aim of the study was to investigate the distribution and association between human papillomavirus (HPV) genotypes and integration as well as their correlation with cervical lesions. Methods Two hundred seven patients diagnosed with high-grade vaginal intraepithelial neoplasia (HG-VaIN) were recruited from the Women's Hospital School of Medicine Zhejiang University between 2015 and 2021 and assayed for HPV genotyping. HPV integration sequencing analysis was conducted using tissues from 53 patients with HG-VaIN and 4 patients with invasive vaginal carcinoma (IVC), along with paired cervical lesion specimens. Results A total of 207 patients with HG-VaIN were categorized as having cervical lesions unrelated to HG-VaIN (group A, 71 patients, 34.30%) or cervical lesion-related HG-VaIN (group B, 136 patients, 65.70%). With an average follow-up of 42.19 months, 12 of 153 patients progressed to IVC and were all from group B. HPV16 infection and the presence of cervical lesions were the 2 main factors associated with disease progression, with cervical lesion coexistence being an independent factor. Compared with group A (5/20, 25%), group B (17/33, 51.52%) showed a higher rate of HPV integration, as demonstrated using HPV integration sequencing analysis, with HPV16 being the most integrated genotype (72.73%). The integration analysis of 4 patients with IVC paired with cervical lesion specimens showed that 3 of the 4 pairs exhibited the same HPV infection and integration sites, indicating a high degree of homology in HPV integration between cervical lesions and HG-VaIN-induced IVC. Conclusions Patients with HG-VaIN associated with cervical lesions exhibited a higher risk of malignant transformation, necessitating more proactive treatment approaches.

Postmenopausal Vaginal and Cervical Cancer Risk Related to In Utero Diethylstilbestrol Exposure

Objectives Women exposed to diethylstilbestrol (DES) in utero have an increased risk of clear cell adenocarcinoma of the lower genital tract, requiring lifelong cervical and vaginal cancer screening. We examined the incidence of DES-related cancers in postmenopausal women 50 years and older. Materials and Methods We conducted a retrospective chart review of patients 50 years and older exposed to DES in utero who received care at our institution. Patients were identified using billing codes and/or searching through the electronic record for the word DES. With this 2-pronged approach, we reviewed a total of 503 charts with confirmed DES exposure to identify gynecologic cancer occurrence. Results Within the 503 selected charts, 28 cases of gynecologic cancer occurrence were identified. Ten patients had cervical cancer and one patient had vaginal cancer. Only 1 woman of 503 developed a DES-related cervical or vaginal malignancy after age 50 years. No patients were diagnosed with cervical or vaginal cancer after age 65 years. Conclusions Diethylstilbestrol-related malignancies are rare in those older than 50 years. Current cervical cancer screening guidelines recommend cessation of screening in an average risk, adequately screened patient at age 65 years, but patients exposed to DES have historically received lifelong screening. However, we found no cases of cervical or vaginal cancer related to DES after age 65 years, suggesting that screening recommendations could be changed for these patients to align with current screening guidelines.

Higher Diagnostic Accuracy of an AI Model for Colposcopy Compared With Conventional and Digital Colposcopic Evaluation

Objective: Colposcopy involves subjective visual assessment of cervical features that may indicate cervical dysplasia. Pattern recognition during colposcopy could be enhanced by artificial intelligence (AI). Using colposcopy images with precisely mapped multiple biopsy sites and corresponding histologic diagnoses, we developed an AI model, Cervix-AID-Net, to classify colposcopy images into low-grade disease [less than cervical intraepithelial neoplasia (CIN) grade 2] and high-grade disease (CIN grade 2 or above). The objective of this study was to compare the diagnostic performance of the Cervix-AID-Net model with the digital colposcope (DySIS) color map and colposcopists’ interpretations of the cervix in identifying low-grade and high-grade disease. Methods: The authors used 3,153 colposcopy images from 178 women, each with 4 biopsies, to train and validate the algorithm. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated with 95% CIs. Results: Cervix-AID-Net achieved a diagnostic accuracy of 99.8% (95% CI: 99.6–99.9) in classifying colposcopy images into low-grade and high-grade categories. This was significantly higher than the DySIS color map accuracy of 58.8% (95% CI: 51.1–66.1) and the accuracy of the colposcopist’s visual impression of the cervix (55.1%, 95% CI: 47.2%–62.5%). Conclusion: This first version of the Cervix-AID-Net demonstrated superior diagnostic accuracy compared with both the DySIS color map and colposcopists’ visual assessment. The results need confirmation in a prospective clinical trial.

The ASCCP Cervical Cancer Screening Task Force Endorsement and Opinion on the American Cancer Society Updated Cervical Cancer Screening Guidelines

Abstract The American Cancer Society (ACS) released updated cervical cancer screening guidelines in 2020 that endorse a shift in practice to primary human papillomavirus (HPV) screening in people with a cervix, beginning at ages of 25–65 years. When access to US Food and Drug Administration–approved primary HPV testing is not available, the ACS offers cotesting or cytology as acceptable alternative strategies but suggests that these testing modalities may be excluded from future iterations of the guidelines. The ASCCP recognizes the benefits and risks of primary HPV cervical cancer screening while acknowledging the barriers to widespread adoption, including implementation issues, the impact of limited HPV vaccination in the United States, and inclusion of populations who may not be well represented on primary HPV screening trials, such as underrepresented minorities. The ASCCP endorses the 2018 US Preventive Services Task Force Recommendation Statement and supports the ACS cervical cancer screening guidelines. Most importantly, the ASCCP endorses any cervical cancer screening for secondary prevention of cervical cancer and recommends interventions that improve screening for those who are underscreened or unscreened.

Prevalence of Positive Cervical Cancer Screening Tests Past the Age of 65 Years With Prior Adequate Negative Screening

Objectives Cervical cancer screening recommendations suggest that cessation can be offered above the age of 65 years if specific prior negative screening criteria are met. We investigated the prevalence of abnormal results in individuals who continue screening despite satisfying the American Society for Colposcopy and Cervical Pathology guidelines for cessation. Materials and Methods In this retrospective study, medical records 2008–2019 from a single urban hospital-based clinic were queried. Charts were manually reviewed to determine which patients met the American Society for Colposcopy and Cervical Pathology exit criteria but continued screening. Findings detected during the extended surveillance period beyond the age of 65 years were analyzed. Results Two hundred ninety-six patients met the criteria of additional screening despite meeting guidelines for cessation. Length of the continued additional surveillance period ranged from 1 to 15 years with a mean of 3.98 years and median of 3 years. Thirty-nine individuals had abnormalities during additional surveillance: 25 high-risk human papillomavirus (HR-HPV) positive only with negative cytology, 8 atypical squamous cells of undetermined significance, 3 low-grade squamous intraepithelial lesions, 2 atypical glandular cells of undetermined significance, and 1 high-grade squamous intraepithelial lesion. No cases of cervical cancer were detected. Total rate of abnormalities including HR-HPV positive only was 332.20 per 10,000 person-years, and cytologic abnormalities alone at 119.25 per 10,000 person-years. Conclusions Most findings were HR-HPV positive with negative cytology, which studies suggest may confer low risk of progression in older individuals. In addition, no patient was found to develop cervical malignancy. Despite controversy regarding this recommendation, our data suggest screening cessation may be appropriate with adequate negative screening history.

Efficacy of Human Papillomavirus Vaccination 4 Years After Conization for High-Grade Cervical Neoplasia

Objective The aim of the study was to estimate human papillomavirus (HPV) vaccination efficacy in reducing recurrence risk within 4 years after conization for high-grade cervical neoplasia. Materials and Methods From January 2012 to June 2015, we performed a longitudinal, observational study (case-series study) on patients diagnosed with cervical intraepithelial neoplasia 2–3 neoplasia. Efficacy was estimated by a 95% CI of the relative risk, relative risk reduction, attributable risk, and number needed to treat. Parametric and nonparametric tests were used as appropriate to compare 160 vaccinated with 171 nonvaccinated patients. To estimate the hazard ratio of the vaccinated status, patients were subjected to multivariable analyses based on the Cox proportional hazard model. To compare recurrence-free survival, a Kaplan-Meier model and a log-rank test were applied. Results The overall recurrence was 9.4% in the nonvaccinated and 2.5% in the vaccinated group (p = .009). Vaccination was associated with a significant decrease in the relative risk (73.5%, 95% CI = 21.8%–90.9%) with a mean number needed to treat of 14 patients per relapse prevented. Although positive conization margins were related to the highest recurrence risk, not being vaccinated independently increased this risk 3.5-fold in a 4-year follow-up (p = .025). Cumulative recurrence-free rates differed significantly between both groups (log-rank test: p = .009). Conclusions Our study corroborates the benefits of HPV vaccination, recommends a closer and longer follow-up in nonvaccinated women, and offers a 4-year prognosis for patients undergoing conization for high-grade cervical lesions.

Fertility and Pregnancy Outcomes After Conservative Management of Adenocarcinoma In Situ of the Cervix

Objective The aim of the study was to evaluate the pregnancy outcomes of women who underwent conservative management of adenocarcinoma in situ (AIS). Materials and Methods We conducted a retrospective chart review of patients diagnosed with AIS at a single tertiary institution between January 1, 1991, and December 31, 2019. We collected demographic data, AIS-specific information, and fertility outcomes and performed bivariate analyses to compare demographic characteristics and AIS-specific information between patients with and without hysterectomy after diagnosis. Patients with conservative management who achieved pregnancy were described. Results Among 87 patients with AIS, 38 (44%) underwent a hysterectomy within 6 months of diagnosis and 49 (56%) underwent conservative management. Six of 19 patients (32%) had residual AIS despite undergoing definitive management after an excisional procedure with negative margins and negative endocervical curettage (ECC). Nine of 19 patients (47%) had residual AIS after an excisional procedure with positive margins and/or a positive ECC. Patients who opted for conservative management were younger (median = 31.6 [interquartile range = 27.4–34.9] vs 38.5 y [32.3–44.8 y], p < .001) and nulligravid. Among patients with conservative management, there were 15 pregnancies and 14 live births (29%). Seven were preterm, although 2 were for medical indications. Conclusions Residual AIS in patients with negative margins and ECC leading to definitive hysterectomy (32%) and the rate of preterm birth (36%) were higher than previous reports and nationally reported rates. However, only 1 patient had a preterm birth before 34 weeks. These findings reflect important information for counseling patients who elect for conservative management of AIS.

The Association Between Clearance of Human Papillomavirus After Conization for Cervical Cancer and Absence of Cancer

Objectives We assessed the relation between clearance of high-risk human papillomavirus (HR-HPV) after large loop excision of the transformation zone (LLETZ) and absence of residual disease, in women diagnosed with cervical cancer (CC) and adenocarcinoma in situ (AIS). Materials Methods Data were collected from 92 women diagnosed with CC and AIS who were positive to HR-HPV and had a repeat cervical HPV test 3–12 weeks after LLETZ (in which CC/AIS were diagnosed) and before final surgical treatment. We compared characteristics of women with negative and positive HR-HPV after LLETZ. Results The HR-HPV results after the LLETZ operation were negative in 40 women and positive in 52 women. The HR-HPV–negative group included a significantly higher incidence of AIS: 14 (35%) vs 5 (9.6%, p < .006). In the negative HR-HPV post-LLETZ group, 36 (90%) had normal histology and only 2 (5%) had cancer in the final histological specimen. Among 34 women who underwent radical hysterectomy/trachelectomy after LLETZ, a normal final histology was observed in 75% and 9% of those who were HR-HPV negative and HR-HPV positive, respectively (p < .0005). The positive predictive value for absence of residual cancer, with clearance of HR-HPV after LLETZ, was 95%. Conclusions Clearance of HR-HPV from the cervix a short time after LLETZ has a high association with the absence of residual cancer in the final outcome, either in the pathology or the follow-up. Testing for HR-HPV a short time after LLETZ might serve as a parameter for risk assessment.

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Loop Electrosurgical Excision Procedure in Managing Persistent Low-Grade Abnormality or Human Papillomavirus Positivity

Objectives The aims of the study were to estimate the rate and to identify predictors of high-grade abnormalities among women with persistent low-grade abnormalities or high-risk human papillomavirus (hrHPV) positivity for at least 2 years stratified by presence (high risk) or absence (low risk) of previous high-grade results or HPV 16/18. Materials and Methods A retrospective cohort study of patients who underwent a loop electrosurgical excision procedure (LEEP) for persistent low-grade or hrHPV positivity was performed. Patients were stratified based on whether they had a history of high-grade and/or HPV 16/18 positivity. Rates of high-grade or worse abnormalities on LEEP were compared using Fisher exact tests. Logistic regression was used to evaluate the associations between patient characteristics and high-grade results on the LEEP. Results Three hundred eleven LEEPs were performed for persistent low-grade or hrHPV positivity. The rates of occult high grade were 12% and 22% among the low- and high-risk groups, respectively. Compared with those 45 years and older, the adjusted odds of high grade was 3.79 (95% CI = 1.19–12.1) for women aged 25–29 years. The odds of high grade was higher among current versus never smokers (6.40; 95% CI = 2.01–20.4) and those with a history of high-grade abnormality (2.23; 95% CI = 1.12–4.43). At 2 years, approximately half had an abnormal cytology and/or hrHPV positivity result independent of whether high grade was identified on their LEEP specimen. Conclusions Patients with persistent low-grade abnormalities or persistent hrHPV should be counseled on the risks and benefits of a LEEP given that 12%–22% have a risk of occult high grade, especially if they have a history of high-grade dysplasia.

Concordant Sum of Cytology and Colposcopy Is Validated by Guidelines to Evaluate the Evolution of Low-Grade Lesions

Self-Collected Vaginal Specimens for HPV Testing: Recommendations From the Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee

Objective The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for the use of self-collected vaginal specimens for human papillomavirus (HPV) testing in health care settings. Methods A comprehensive literature search was performed, external systematic reviews were evaluated, and HPV genotype agreement between self-collected vaginal and clinician-collected cervical specimens was summarized. Recommendations considered available data, public comments, and expert consensus. Recommendations were ratified through a vote by the Consensus Stakeholder Group. Results Clinician-collected cervical specimens are preferred and self-collected vaginal specimens are acceptable for primary HPV screening of asymptomatic average-risk individuals. Repeat testing in 3 years is recommended following HPV-negative screens using self-collected vaginal specimens. Colposcopy with collection of cytology and biopsies is recommended following positive tests for HPV types 16 and 18. Clinician-collected cytology or dual stain for triage testing is recommended following positive tests for HPV 45, 33/58, 31, 52, 35/39/68, or 51 or for pooled HPV other types but negative for HPV 16 or 18. Repeat HPV testing in 1 year is recommended following a positive test for HPV types 56/59/66 and no other carcinogenic types. Minimal data exist on use of self-collected vaginal specimens for surveillance following abnormal screening test results, colposcopy or treatment, and therefore, clinician-collected cervical specimens are preferred. Conclusions Human papillomavirus testing of self-collected vaginal specimens expands cervical cancer screening options and has potential to increase access for currently underscreened individuals. Laboratory and clinical workflows will need to be modified to ensure adequate specimen processing and follow-up.

The Natural History of Cervical Intraepithelial Neoplasia Grades 1, 2, and 3: A Systematic Review and Meta-analysis

Objective The aim of the study was to obtain an updated overview of regression, persistence, and progression rates of conservatively managed cervical intraepithelial neoplasia grade 1 (CIN 1)/CIN 2/CIN 3. Methods Data sources were MEDLINE, Embase, and Cochrane (January 1, 1973–April 14, 2020). Two reviewers extracted data and assessed risk of bias. To estimate outcome rates, we pooled proportions of the individual study results using random-effects meta-analysis, resulting in point estimates and corresponding 95% CIs. Heterogeneity was quantified by the I 2 and τ2 measures. Results Eighty-nine studies were included, 63 studies on CIN 1 (n = 6,080–8,767), 42 on CIN 2 (n = 2,909–3,830), and 7 on CIN 3 (n = 245–351). The overall regression, persistence, and progression to CIN 2 or worse and CIN 3 or worse rates for women with conservatively managed CIN 1 were 60% (95% CI = 55–65, I 2 = 92%), 25% (95% CI = 20–30, I 2 = 94%), 11% (95% CI = 8–13, I 2 = 89%), and 2% (95% CI = 1–3, I 2 = 82%), respectively. The overall regression, persistence, and progression rates for CIN 2 were 55% (95% CI = 50–60, I 2 = 85%), 23% (95% CI = 19–28, I 2 = 83%), and 19% (95% CI = 15–23, I 2 = 88%), respectively. Finally, for CIN 3, these were 28% (95% CI = 17–41, I 2 = 68%), 67% (95% CI = 36–91, I 2 = 84%), and 2% (95% CI = 0–25, I 2 = 95%), respectively. Cervical intraepithelial neoplasia grade 2 regression was significantly higher in women 30 years or younger and high-risk human papillomavirus–negative women (66%, 95% CI = 62–70, I 2 = 76%; 94%, 95% CI = 84–99, I 2 = 60%). Only 2/7,180 (0.03%) and 10/3,037 (0.3%) of the CIN 1 and CIN 2 cases progressed to cervical cancer. Conclusions Most CIN 1/CIN 2 will regress spontaneously in less than 24 months, with the highest rates in high-risk human papillomavirus–negative and young women, whereas progression to cancer is less than 0.5%. Conservative management should be considered, especially in fertile women and with expected high compliance. Given the heterogeneity in regression rates of high-grade histology, this should be classified as CIN 2 or CIN 3 to guide management.

A Cross-sectional Study on the Prevalence of Cervical Dysplasia Among Women With Female Genital Mutilation/Cutting

Objective The aim of the study was to assess the prevalence of cervical dysplasia among migrant women with female genital mutilation/cutting (FGM/C) at a specialized clinic in Switzerland. Materials and Methods This is a descriptive retrospective cross-sectional study. We reviewed the electronic medical records of all women who attended a specialized FGM/C clinic at the Geneva University Hospitals between 2010 and 2016. We examined sociodemographic data, sexually transmitted infections, FGM/C types, Pap smear results, and follow-up in women diagnosed with cervical dysplasia. Results Three hundred sixty records were reviewed and 338 women were included. The average age was 33 years (SD = 7.47 years). Most women were from Eritrea and Somalia (n = 204, 60.4%) and had FGM/C type III (n = 188, 55.6%). A total of 12.4% (n = 42) of the patients had abnormal Pap smears: 1.5% (n = 5) with atypical squamous cells of undetermined significance (ASCUS) with high-risk human papillomavirus (HPV), 7.9% (n = 27) with low-grade squamous intraepithelial lesion (LSIL), and 2.9% (n = 10) with high-grade squamous intraepithelial lesion or higher (HSIL +). Of the 37 patients with dysplasia, 22 (59.4%) completed follow-up and 15 (40.5%) received incomplete follow-up. Conclusions The prevalence of high-grade squamous intraepithelial lesion+ among migrant women with FGM/C is high (2.95%) compared with the general Swiss population (0.58%). Follow-up for cervical dysplasia must be improved by increasing provider knowledge of this patient population and by addressing barriers to care.

Onclarity Performance in Human Papillomavirus DNA Detection in Formalin-Fixed Paraffin-Embedded Cervical Samples

Objectives Diagnosis of HPV infection is usually performed from cervical liquid-based cytology specimens (LBC), but these often contain a large amount of human papillomavirus (HPV) genotypes, most of which might cause transient infections. The aim of the study was to evaluate the performance of BD Onclarity HPV test genotyping method on formalin-fixed, paraffin-embedded (FFPE) cervical specimens compared with genotyping results from LBC. Materials and Methods Formalin-fixed, paraffin-embedded specimens from women surgically treated for cervical intraepithelial lesions (CINs) at the European Institute of Oncology, Milan, from September 2012 to June 2013 were retrieved from the archives of the Department of Pathology of the European Institute of Oncology. The FFPE and LBC specimens were genotyped using the same extended genotyping Onclarity assay. Results We collected 99 samples (26 CIN 1, 30 CIN 2, and 43 CIN 3+), but 15 were excluded from the analysis: these 84 samples show an overall agreement of 89% for HPV status between FFPE Onclarity samples versus LBC samples. The FFPE and LBC samples showed identical genotype in 75% samples, compatible genotype (at least 1 of the genotypes detected in LBC sample was found in the tissue sample) in 14% specimens, and discrepant genotype in 11% samples. Conclusions Our data demonstrate a very good concordance between HPV genotypes found in cytological and tissue samples, suggesting that the Onclarity method could also be used to detect HPV in tissue samples and that the HPV genotype detected in FFPE samples is one of the HPV detected in cytological samples, supporting the thesis that one lesion is caused by one HPV genotype.

Efficacy of a Coriolus versicolor–Based Vaginal Gel in Women With Human Papillomavirus–Dependent Cervical Lesions: The PALOMA Study

Objective The aim of the study was to evaluate the efficacy of Papilocare, a Coriolus versicolor–based vaginal gel, in repairing human papillomavirus (HPV)-related low-grade cervical lesions. Methods The study is a multicenter, open-label, randomized, parallel-group, watchful waiting approach-controlled trial involving 91 HPV-positive women with low-grade Pap smear alterations and consistent colposcopy. Results The percentage of patients with normal Pap smear and concordant colposcopy 3 and 6 months after receiving treatment (78.0% and 84.9%) was significantly higher than without treatment (54.8% and 64.5%), especially in high-risk HPV patients (79.5% and 87.8% vs 52.0% and 56.0%). At 6-month visit, overall HPV clearance was achieved by a greater number of patients receiving treatment (59.6%) compared with those without treatment (41.9%), especially high-risk HPV ones (62.5% vs 40.0%). The cervical re-epithelization score was significantly higher with treatment (mean = 4.5) than without (mean = 4.1). Compared with baseline, perceived stress decreased in the treatment group (from 21.1 to 19.0) and increased in the control group (from 17.7 to 20.7). A total of 7 possible or probable treatment-related adverse events were reported, most of them (n = 6) being mild or moderate in severity. Conclusions Treatment with Papilocare has demonstrated a better clinical benefit than the conventional watchful waiting approach in clinical practice for total and high-risk HPV patients in terms of its efficacy to treat HPV-related cervical lesions and to clear all HPV strains after a single 6-month period. It has demonstrated an adequate safety and tolerability and confers additional benefits such as higher re-epithelization, stress reduction, and high treatment adherence.

Follow-up After Loop Electrosurgical Excision of Cervical Intraepithelial Neoplasia: The Use of Combined Cytology and Human Papillomavirus Testing

Objectives The aims of the study were to investigate how many women after 1 or 2 follow-up examinations, based on combined cervical cytology and human papillomavirus (HPV) testing, could finish posttreatment follow-up and continue with the general screening program and to determine the 5-year risk of recurrence in this group. Methods This is a prospective observational study that includes women, who underwent loop electrosurgical excision procedure (LEEP) in the North Denmark Region, from January 1, 2012, to May 31, 2014. All included women had histologically verified diagnosis of high-grade cervical intraepithelial neoplasia (CIN 2+) or adenocarcinoma in situ (AIS) before LEEP and posttreatment follow-up with cervical cytology and HPV combination testing. Study period was until October 2019. Results Totally, 563 women were included in the study. After finishing the posttreatment follow-up, 439 (78%) could continue to the general screening program and 362 of them had a screening during the study period. Six women (1.7%) had either cervical dysplasia and/or HPV infection in the cervical screening, and of these, 3 (0.8%) had high-grade dysplasia corresponding to CIN 2. None was diagnosed with CIN 3, AIS, or invasive carcinoma. One hundred twenty-one women (36%) chose to be screened sooner than recommended in the national guidelines. Conclusions Human papillomavirus and cytology combination test after LEEP allows women, irrespective of margin status, safely to continue with the general screening program after a short posttreatment follow-up period. Improved information is mandatory to reduce “opportunistic” screening after finishing posttreatment follow-up.

Would Women With Solid Organ Transplant Qualify for Triennial Cervical Cancer Screening as Recommended by the American College of Obstetricians and Gynecologists in 2016 and American Society for Colposcopy and Cervical Pathology in 2019?

Objective The aim of the study was to assess the applicability and safety of cervical cancer screening guidelines recommended by the American College of Obstetricians and Gynecologists (2016) and American Society for Colposcopy and Cervical Pathology (2019) for women with solid organ transplants (SOTs). Materials and Methods We analyzed data previously abstracted through December 2015 for 971 women (18–60 y) who received their first SOT at Mayo Clinic (Rochester, MN) from January 17, 1995, through December 31, 2011. Inclusion criteria were initial benign findings on cervical cytology after SOT and at least 1 subsequent cytologic screening. Results Of 415 women whose initial cytologic findings were benign, 310 met inclusion criteria. The cumulative incidence of abnormal cervical cytology among these 310 women was 4.3% (95% CI = 1.9%–6.7%) by 30 months and 11.2% (95% CI = 7.1%–15.4%) by 60 months after their initial benign results. Considering all women with SOT, 68.4% (284/415) had no documented abnormal cytologic findings within 60 months (26 had abnormality; 284 no abnormality; and 105 not assessed). In women with negative tests for human papillomavirus, high-grade squamous intraepithelial lesions were not documented on cytology with variable duration of follow-up. No cervical squamous cell carcinoma was identified. Conclusions Of women with initial benign cervical cytology after SOT, more than two thirds would have been eligible for extended-interval screening. Further study is needed, particularly regarding the role of high-risk human papillomavirus testing.

Criminal Justice Involvement and Abnormal Cervical Cancer Screening Results Among Women in an Urban Safety Net Hospital

Objective The aim of the study was to elucidate the risk factors underlying abnormal cytology-based cervical cancer screening (Pap testing) in justice-involved women (JIW) compared with non-JIW in an urban safety net hospital. Methods Retrospective chart review of women with a history of correctional involvement who received care at Grady Health System between 2010 and 2018 and had a Pap test was performed (n = 191). An age-matched cohort of women with no correctional involvement and had a Pap test at Grady served as the control (n = 394). Variables of interest were age, HIV, smoking, race, mental health history, and history of incarceration. Outcomes of interests were rate of abnormal Pap tests and follow-up. χ2 and logistic regression models evaluated associations between the variables of interest and outcomes. Results Rates of abnormal Pap tests were significantly higher in JIW (35.6%) than controls (18.5%, p < .0001). Compared with controls, JIW were significantly more likely to have high-grade cervical cytology (odds ratio [OR] = 3.89, p < .0005) and be lost to gynecologic follow-up (OR = 8.75, p < .0001) and a history of severe mental illness (29.5% vs 4.3%, p < .0001). Those with abnormal Pap tests were likely to be HIV-positive (OR = 20.7, p < .001) and have a history of incarceration (OR = 2.33, p < .001). Predictors of high-grade Pap test were smoking history (OR = 0.16, p = .014), HIV-positive (OR = 3.66, p = .025), and history of incarceration (OR = 3.96, p < .0005). Conclusions Justice-involved women represent a high-risk subpopulation with significantly increased rates of high-grade cytology and lost to follow-up. This underscores the need for attention to screening programs and follow-up interventions for JIW.

Survival of Older Women With Cervical Cancer Based on Screening History

Objective A population-level retrospective cohort study was conducted to determine the influence of cervical screening history on the survival from cervical cancer in women 50 years or older. Methods The study included women diagnosed with invasive cervical cancer in Ontario, Canada, between 2005 and 2012, who were followed for at least 4 years. Screening history was observed for the 5 years before diagnosis. Health care administrative databases were linked to determine demographic, affiliation with primary care physicians, stage (available 2010–2012), treatment, and survival data. Kaplan-Meier and multivariate analyses were carried out to evaluate the impact of cervical screening on overall survival (OS). Results There were eligible 1,422 women diagnosed with invasive cervical cancer between 2005 and 2012 of whom 566 had been screened within the 5 years before diagnosis. There were 856 women who did not undergo screening within the 5 years before diagnosis. Unscreened women were more likely to present with locally advanced disease (69.3%) compared with the screened women (42.9%). Four-year OS was significantly greater in the screened group (79.9% vs 58.2%). In our univariate analysis, screening was significantly related to survival (hazard ratio = 2.1, p < .01). In our multivariate analysis after adjusting for age, treatment, affiliation with a primary care physician, and income, screening was still significantly associated with improved survival (hazard ratio = 1.5, p < .01). Conclusions Our results demonstrate a survival benefit to screening in women 50 years or older who are diagnosed with cervical cancer. Screening participation must be encouraged in women older than 50 years as rates decline in this age group.

Evaluation of Cobas HPV and SeqHPV Assays in the Chinese Multicenter Screening Trial

Objective The aim of the study was to evaluate the Cobas 4800 Assay and the SeqHPV Assay with self (S) and direct (D) cervical samples in the Chinese Multicenter Screening Trial (CHIMUST). Materials and Methods The CHIMUST is a large population-based multicenter clinical trial, and 10,885 women aged 30–59 years from 15 sites in 7 provinces with no cervical cancer screening for 3 years were eligible. All participating women contributed one self-collected sample (S) and 1 physician-collected endocervical sample (DL). The self-collected sample was first applied to the solid media transport card (SS), and then, the brush placed in 6 mL of ThinPrepSolution (SL). All samples were tested with Cobas 4800 and SeqHPV high-risk HPV assays. Patients human papillomavirus positive (self or direct) were recalled for colposcopy and biopsies. Results A total of 10,399 women had complete data. The mean age was 43.9 years. A total of 1.4% (142/10,399) had cervical intraepithelial neoplasia (CIN) 2+ and 0.5% (54/10,339) had CIN 3+. In the liquid specimens, the overall HPV infection rates were 10.8% for Cobas and 10.9% for SeqHPV in D sample, and 13.7% for Cobas and 11.6% for SeqHPV in SL sample, respectively. The sensitivity of Cobas-DL, Cobas-SL, SeqHPV-DL, and SeqHPV-SL for CIN 2+ was 95.07%, 95.07%, 94.33%, and 96.48%, respectively. The specificity of Cobas-DL, Cobas-SL, SeqHPV-DL, and SeqHPV-SL for CIN 2+ was 90.38%, 87.35%, 90.21%, and 89.53%, respectively. There were no differences in sensitivity when applying the 2 assays to both self- and directly collected samples in liquid transport media (p > .05). Conclusions Both Cobas and SeqHPV screening assays using both self-collected and directly endocervical collected specimens demonstrate similar sensitivity for the detection of CIN 2+ and CIN 3+.

Follow-up Findings in Postconservative Treatment Surveillance for Women With Cervical Adenocarcinoma In Situ

Objectives The risks of adenocarcinoma in situ (AIS) recurrence or progression after conservative treatment are uncertain. The aim of this study was to examine the role of high-risk human papillomavirus (hrHPV) and cytology in the posttreatment surveillance of AIS patients. Materials and Methods Follow-up results of hrHPV status, cytology results, and clinicopathological features of 207 patients were retrospectively analyzed, in whom AIS was initially treated by loop electrosurgical excision procedure (LEEP)/cone biopsy between September 2009 and June 2018. Results Among 207 patients diagnosed AIS on LEEP/cone biopsy, 30.9% (64/207) had positive margins. Persistent/recurrent AIS rate was substantially higher in the patients with positive margins than in those with negative margins (47.2% vs 9.3%, p < .001). Of 74 patients with hrHPV surveillance, 17 (17/74, 23.0%) were found to have positive hrHPV and 4 (4/17, 23.5%) had the persistent/recurrent AIS regardless of margin status. On the contrast, no AIS were found in negative surveillant hrHPV patients (23.5% vs 0%, p < .001). Lastly, 27.8% patients (22/79) were reported atypical glandular cells on surveillant cytology, and 9 persistent/recurrent AIS cases were further identified on second biopsy or hysterectomy with a positive detection rate of 40.9%. Conclusions In this study, we concluded the positive margin on LEEP/cone biopsy in AIS patients was associated with a significantly greater risk of disease persistence or recurrence. The posttreatment surveillance by cytology and adjunct hrHPV would be an ideal strategy in predicting AIS persistence and recurrence, which will warrant further treatments.

Anal Cancer and Anal Cancer Screening Knowledge, Attitudes, and Perceived Risk Among Women Living With HIV

Objectives The aims of the study were (1) to describe anal cancer knowledge, perceived risk, screening barriers, and acceptability of sample self-collection among women living with HIV (WLWH) at an integrated safety-net system and (2) to describe differences in demographic and psychosocial variables among a subsample of WLWH with a history of abnormal cervical cytology results versus those with normal results. Materials and Methods We conducted telephone surveys with English- and Spanish-speaking WLWH (N = 99) and used electronic health record data to extract insurance type, CD4+ cell count, RNA viral load, and cervical cytology results. We calculated descriptive statistics for participant demographics, HIV laboratory results, and psychosocial variables. Among the subsample of women who completed a recent cervical Pap, we used Fisher exact test to assess differences in demographic variables, CD4+ counts, RNA viral loads, knowledge, awareness, acceptability, and perceived risk by cervical cytology results. Results Most participants (70%) reported knowing nothing about anal cancer; 28% correctly responded that HIV increases one’s chance of getting anal cancer. Most (68%) never heard of an anal Pap test. Forty percent would get an anal Pap if they could self-collect the sample, whereas 59% were neutral or disagreed. The 2 most commonly cited barriers to obtaining an anal Pap were “I do not know enough about it” (n = 15) and “It might hurt” (n = 9). Conclusions This study highlights a gap in knowledge and awareness among WLWH regarding their heightened risk for anal cancer. It indicates the need for health education and suggests an opportunity for a self-collection intervention.

Screening History and Survival Among Women With Cervical Cancer in Puerto Rico

Objectives Cervical cancer incidence is rising in Puerto Rico (PR). Screening for cervical cancer could prevent the occurrence of the disease or lead to its early detection, translating to survival benefits. In this study, we evaluated the association of cervical cancer screening status with tumor diagnosis and survival among Hispanic women living in PR. Methods We analyzed data for 506 incident cases of primary cervical cancer diagnosed from the period 2011–2014, identified through the PR Central Cancer Registry. We ascertained screening status 3 years before cervical cancer diagnosis using data from the period 2008–2014 from the PR Central Cancer Registry-Health Insurance Linkage Database. Patients were followed until 2019. Our outcomes of interest were stage at diagnosis and survival. Results Most women (78.86%) were covered by public insurance (Medicare and/or Medicaid), and 69.57% underwent screening 3 years before their diagnosis. The proportion of cases diagnosed with localized stage was significantly greater among the screened group compared with those unscreened (43.5% vs 33.1%, p < .0001). Multivariate analysis showed that women insured through Medicaid were less likely to have been screened when compared with women with private insurance (odds ratio = 0.29; 95% CI = 0.16–0.52). Five-year survival was significantly greater among screened (72%) than unscreened (54%) women (plog-rank < 0.05). The multivariate Cox proportional hazards model showed that women who received screening had a 39% (hazard ratio [HR] = 0.61; 95% CI = 0.43–0.87) lower risk of death compared with unscreened women. Conclusion Our findings exemplify survival benefits among women who underwent cervical cancer screening in PR. Interventions to improve screening uptake and adherence are a public health priority.

Colposcopy Standards: Guidelines for Endocervical Curettage at Colposcopy

Objective The most recent guidelines for colposcopy practice in the United States, the 2017 Colposcopy Standards Consensus Guidelines, did not include recommendations for endocervical curettage (ECC). This document provides updated guidelines for use of ECC among patients referred for colposcopy. Methods Consensus guidelines for the use of ECC were developed in 2012. To update these guidelines in concordance with the 2017 Colposcopy Standards process, an expert workgroup was convened in 2021. Literature had been previously reviewed through 2011, before the 2012 guideline. Literature from the years 2012–2021 and data from the NCI Biopsy study were reviewed, focusing on the additional yield of ECC. Results Endocervical curettage is recommended for patients with high-grade cytology, human papillomavirus 16/18 infection, positive results on dual staining for p16/Ki67, for those previously treated for known or suspected cervical precancer or considering observation of cervical intraepithelial neoplasia grade 2, and when the squamocolumnar junction is not fully visualized at colposcopy. Endocervical curettage is preferred for all patients aged older than 40 years. Endocervical curettage is acceptable for all nonpregnant patients undergoing colposcopy but may be omitted when a subsequent excisional procedure is planned, the endocervical canal does not admit a sampling device, or in nulliparous patients aged younger than 30 years, with cytology reported as atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion regardless of whether the squamocolumnar junction is fully visualized. Endocervical curettage is unacceptable in pregnancy. Conclusions These guidelines for ECC add to the 2017 consensus recommendations for colposcopy practice in the United States.

Genotyping and Cytology Triage of High-Risk HPV DNA Positive Women for Detection of Cervical High-Grade Lesions

Objective A demonstration project of primary human papillomavirus (HPV) testing was initiated in 2011 among more than 23,000 women attending routine cervical cancer screening. We examined the additional diagnostic performance of HPV genotyping for detecting disease in women with abnormal cytology. Methods Women aged 30 to 65 years were originally screened for HPV using Hybrid Capture II test. Women with positive results were triaged using conventional cytology, and those with atypical squamous cells of undetermined significance or worse (≥ASC-US) were referred to colposcopy. We retrospectively genotyped (Roche cobas 4800 HPV system [Roche Molecular Systems Inc, Pleasanton, CA]) cervical specimens that were HPV+ with Hybrid Capture II test and extracted women's medical history postbaseline screening. We calculated positive predictive values (PPVs) and 95% confidence intervals (CIs) of triage tests to detect histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) within the first year of follow-up among women positive for HPV16, HPV18, and HPV16 and/or HPV18 as well as among those negative for HPVs 16 and 18. Results Of 1,396 HPV-positive women, 1,092 (78%) were classified as normal, 136 (10%) had CIN1, 80 (6%) had CIN2, 81 (6%) had CIN3, and 7 women had cancer throughout the entire follow-up period. Seventy CIN2+ cases were detected within the first year of follow-up. The PPV for detecting CIN2+ was 20.9% (63/239; 95% CI = 16.4–25.9) for ASC-US+ cytology. In women with ASC-US+, PPVs were 31.2% (24/77; 95% CI = 21.1–42.7) for HPV16+, 27.8% (5/18; 95% CI = 9.7–53.5) for HPV18+, 30.8% (28/91; 95% CI = 21.5–41.3) for HPV16+ and/or HPV18+ women, and 16.6% (35/211; 95% CI = 11.8–22.3) in women testing negative for HPVs 16 and 18. Conclusion Partial genotyping as an additional triage strategy to cytology can markedly improve clinical diagnostic performance.

HPV Test as Test of Cure After Conization for CIN2+: A Nationwide Register-Based Cohort Study

Objective The purpose of this study was to assess if cytology can be omitted in the follow-up after treatment for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and if human papillomavirus (HPV) test can be used alone as test of cure (TOC) after stratifying for resection margins. Material and Methods In this retrospective register-based study, women who had a conization performed in Denmark between January 1 and December 31, 2013, were included. Histology, cytology, and HPV test results were obtained from The Danish Pathology Data Bank for a 3-year follow-up. Results A total of 5,174 women were included, of whom 6.1% (318/5,174) had histological residual/recurrent disease in the follow-up period. In the group with free margins, 2.6% (73/2,780) had residual/recurrent disease in contrast to 10.2% (245/2,394) in the group with involved margins. In the group with free resection margins and negative HPV test results, residual/recurrent disease was found in 0.5% (13/2,780) compared with 0.3% (9/2,780) in the group with negative HPV test results and normal cytology at 6 months′ follow-up. Based on margin status and HPV test result as follow-up, the sensitivity, specificity, and positive and negative predictive values were 95.9%, 43.2%, 10.0%, and 99.4% respectively, and for combined testing (margin status, HPV, and cytology), 97.2%, 41.2%, 9.8%, and 99.6%, respectively. Conclusions Using the HPV test at the first post-treatment control as TOC for cervical intraepithelial neoplasia grade 2 or worse after stratifying for resection margins in cone resections yields an equally high sensitivity and negative predictive value as cotesting with cytology. We suggest that women with free resection margins return to the routine screening program after negative HPV test result as TOC at 6 months.

Recurrent Dysplasia After a Loop Electrosurgical Excision Procedure: Local Versus General Anesthesia

Objective This study aimed to compare the rates of positive specimen margins and postconization recurrent dysplasia between loop electrosurgical excision procedures (LEEPs) performed under general anesthesia (GA) and LEEP under local anesthesia (LA). Methods This retrospective cohort study included all consecutive women who underwent LEEP between 2011 and 2019. Collected data included demographics, LEEP indication, cone dimensions, and margin involvement as well as recurrence rate. Women who had undergone previous conization, cold-knife conization, or those who were lost to follow-up during the first 2 years after the procedure were excluded. Results Overall, 71 women who underwent LEEP under GA and 75 women under LA were included. Demographic characteristics were similar between the groups, as were the rates of preceding abnormal cytology and high-grade dysplasia before conization. Although cone depth and volume were higher for LEEP specimens done under GA compared with LA, the rate of positive specimen margins was comparable both for the endocervical margin (16/71 [22.5%] vs 16/75 [21.3%], respectively; p = .861) and the ectocervical margin (14/71 [19.7%] vs 11/75 [14.7%], respectively; p = .418). During the first 2 years after conization, the rates of high-grade dysplasia (cervical intraepithelial neoplasia ≥ 2) in repeat biopsy and the need for repeat conization were also not significantly different between the GA and LA groups (4.2% vs 1.3%, p = .356; 7.0% vs 9.3%, p = .614, respectively). Conclusions Anesthesia mode does not seem to affect the rate of positive LEEP margins and the need for repeat conization. Our study findings suggest that LA should be preferred instead of GA in LEEP.

Disparities in Diagnosis and Treatment of Cervical Adenocarcinoma Compared With Squamous Cell Carcinoma: An Analysis of the National Cancer Database, 2004–2017

Objectives The aim of the study are to compare trends in diagnosis and treatment of adenocarcinoma of the cervix (AC) to squamous cell carcinoma of the cervix (SCC) and to examine associations between stage at diagnosis and guideline-concordant treatment with race, age, and insurance type for AC and SCC. Materials and Methods We performed a retrospective cohort study of cervical AC (n = 18,811) and SCC (n = 68,421) from the 2004–2017 National Cancer Database. We used generalized linear models to evaluate trends in frequency of histologies and to evaluate associations between race, age, and insurance status with stage of diagnosis and receipt of National Comprehensive Cancer Network guideline–concordant treatment for AC and SCC. Results The proportion of AC relative to SCC increased from 19.4% (95% CI = 18.4–20.5) to 23.2% (95% CI = 22.2–24.2) from 2004 to 2017 (p < .001). Compared with SCC, women with AC were younger, more likely to be White, and privately insured (p < .001). Older women with AC were 44% less likely to be diagnosed with early-stage disease than younger women (adjusted relative risk = 0.56, 95% CI = 0.52–0.60); there was no significant difference for SCC. Black women with AC were 16% less likely to be diagnosed with early-stage disease (adjusted relative risk [aRR] = 0.84, 95% CI = 0.79–0.89) than White women. Women with public insurance were less likely to be diagnosed at an early stage for both AC (aRR = 0.81, 95% CI = 0.78–0.84) and SCC (aRR = 0.79, 95% CI = 0.77–0.81). Rates of guideline-concordant treatment were similar for AC and SCC, with minimal differences by age, race, and insurance. Conclusions As the proportion of AC to SCC rises, important race and age-related disparities must be addressed to reduce unnecessary morbidity and death.

Diagnostic Utility of Endocervical Curettage During Colposcopy Among Patients of Varying Risk Factors

Objective Endocervical curettage (ECC) during colposcopy is recommended in certain circumstances; however, diagnostic use remains unclear. We evaluate the utility of ECC among patients with non-fully visualized squamocolumnar junction (SCJ) and certain patient socioeconomic factors. Methods Retrospective chart analysis was completed for patients aged older than 21 years who underwent a colposcopy at 2 study sites between 2012 and 2021. Demographics and histopathologic results were analyzed. Results A total of 1,516 colposcopies were reviewed; 73.8% (n = 1,119) had an ECC with colposcopy. Of those, 92.1% (n = 1,031) had benign ECC whereas 13.9% (n = 156) had a positive ECC at time of colposcopy. Most patients with benign ECC had benign/low-grade squamous intraepithelial lesion pathology on colposcopy biopsy (82.3%; n = 914; p < .001), and most patients with high-grade squamous intraepithelial lesion (HSIL) on ECC had HSIL on colposcopy biopsy (63.4%; n = 52; p < .001) However, when looking at patients with high-grade pathology on colposcopy biopsy, it was seen that most had benign or low-grade squamous intraepithelial lesion on ECC (79.5%; n = 205; p < .001). Most patients with adequately visualized SCJ on colposcopy were noted to have HSIL on biopsy and negative ECC (73%; n = 81; p < .001). This result was similar in patients with non-fully visualized SCJ, although not statistically significant. When stratified by socioeconomic status, most patients with high-grade lesions had a benign ECC. Conclusions Endocervical curettage has been described to increase the identification of high-grade lesions at time of colposcopy. This descriptive study shows that many high-grade lesions at time of excisional procedure had a benign ECC on colposcopy, with no demonstrated clear additional utility in high-risk groups.

Understanding Perceived Barriers to Colposcopy Follow-Up Among Underserved Women at an Urban Teaching Hospital: A Qualitative Study

Objective Loss to follow-up after abnormal cervical cancer screening disproportionately impacts underserved populations. Our objective was to identify perceived barriers to follow-up after abnormal Pap smear among underserved women. Methods Women with abnormal Pap smear presenting for colposcopy at an urban teaching hospital were asked to participate in qualitative interviews. A topic guide was developed to assess knowledge about cervical cancer screening and perceived barriers to follow-up. A demographic survey was completed and interviews were recorded and transcribed. Responses were coded and placed into a framework: intrapersonal, interpersonal, and community barriers. Major themes and subthemes were identified. Demographic data were reported descriptively. Results Of 24 women enrolled, 18 (75%) completed full interviews. Median age was 38 years (range = 21–64). Participants were racially diverse: 10 (56%) Hispanic, 7 (39%) non-Hispanic White, 1 (5.5%) non-Hispanic Black, and 1 (5.5%) Asian, and all had public insurance. Seven (39%) presented for their 1st colposcopy visit and 11 (61%) had previous visits. Seventeen (94%) had a positive human papillomavirus test and 7 (39%) had atypical squamous cells of undetermined significance. The most common themes identified were related to knowledge gaps, including lack of understanding of Pap smears/human papillomavirus and cervical cancer risk factors. Most participants were satisfied with provider communication but dissatisfied with communication with the office, like scheduling appointments. Conclusions Despite positive patient perception of physician communication, knowledge was most commonly identified as a barrier to colposcopy follow-up. Implementing a web-based intervention addressing knowledge gaps may improve abnormal cervical cancer screening follow-up among this population.

Endocervical Margins Status in Excision for Preventing Cervical Cancer According to the Transformation Zone Type

Objective The aim of this study is to assess the outcomes of 610 excision types I and II in a referral facility as a function of transformation zone (TZ) types. Methods This is a retrospective cohort study of women with cervical precursor lesions who underwent loop electrocautery excision procedure from 2017 to 2019 at the University of Campinas. The primary outcome was endocervical margin status, negative or positive. Other variables were excision type (I/II), TZ (1/2/3), age, menopausal status, hormonal contraceptives, smoking, and sexual debut. Tests used were chi-square or Fisher exact, Mann-Whitney, and simple and multiple logistic regression. Results The most frequent was TZ 1 (62.5%). Excision II was the most frequent: 54.1% in TZ 1, 67.2% in TZ 2, and 82.1% in TZ 3. A negative margin was observed in TZ 1, 76.0% when excision I and 86.4% when excision II (p = .009); TZ 2, 86.4% when excision I and 88.9% when excision II (p = .672); and TZ 3, 76.5% when excision I and 78.9% when excision II (p = .672). Multivariate analysis revealed in TZ 1 a 2.12 (1.23–3.65) higher risk of obtaining a negative margin in excision type II. In TZ 2 and 3, none of the variables predicted the chance of a negative margin. Conclusions The endocervical margin was negative in 3 in every 4 women who underwent loop electrocautery excision procedure, regardless of excision type. Age, menopausal status, smoking, and hormonal contraception did not predict margin status.

Improving Colposcopy Education Through Images: A Preliminary Assessment of an Image-Based Mobile App for Colposcopic Education

Objectives Colposcopy is an indispensable part of cervical cancer screening. However, in most training programs, there is little by way of a formalized curriculum. We created an image-based teaching tool and hypothesized that this tool, in a mobile app format, would increase resident comfort with colposcopic practice and quantitatively increase their ability to correlate colposcopic images with impressions. Materials and Methods This was a pilot study conducted among ObGyn residents during March 2021. Thirty-eight residents participated and were randomized to either an app user or an independent study control group. Both groups were surveyed before and after their assigned training and completed a postintervention standardized cognitive examination. The primary end points were subjective improvements in comfort with colposcopy. The secondary end point was performance on a standardized image quiz. Results Of the 46 targeted residents, 38 participated and 26 completed all elements of the study. On the image examination, app users performed slightly better when compared with the independent study group (mean score, 14.9/25 [SD = 2.15] vs 14.0/25 [SD = 3.27], p = .39). App users also were more likely to be confident in providing an overall colposcopic impression (73% vs 30%, p = .111). One hundred percent of the participants in the app user group said that they would recommend the tool to other residents and residency programs. Conclusions Image-based teaching tools, such as the ICE-TI app, are valued by learners and can be a useful adjunct to standardized colposcopy curricula. In addition, making use of a mobile platform facilitated convenience learning.

Risk-Based Cervical Consensus Guidelines: Methods to Determine Management if Less Than 5 Years of Data Are Available

Objectives In the 2019 ASCCP Risk-Based Management Consensus Guidelines, clinical management decisions are based on immediate and 5-year cervical intraepithelial neoplasia (CIN) 3+ risk estimates. However, data for technologies other than human papillomavirus testing and cytology may be limited to clinical trials and observational studies of shorter duration than 5 years. To enable decisions about 1- or 3-year intervals, 3-year CIN 3+ risk equivalents to 5-year CIN 3+ risk thresholds were generated. Materials and Methods We examined screening test result scenarios around the 5-year risk thresholds of 0.15% and 0.55% and calculated the average percent increase in CIN 3+ risk from 3 to 5 years. Using this average increase, we obtained estimates of corresponding risk thresholds at 3 years. We then validated whether use of the 3-year risk threshold would have resulted in equivalent management per the 2019 recommendations. Results Around the 5-year CIN 3+ risk threshold of 0.55%, the average increase in risk from 3 to 5 years was 0.16%. Therefore, the equivalent threshold for 3-year risk was estimated as 0.39%. We found no difference in recommendations to return in 1 or 3 years using the 3-year or 5-year risk thresholds in 66 of the 67 scenarios (98.5%) in follow-up in 2019 guidelines. Conclusions In this methodological addendum, the Enduring Guidelines Committee adopted the use of the 0.39% 3-year CIN 3+ risk threshold as equivalent of the 0.55% 5-year CIN 3+ risk threshold for technologies with fewer than 5 years of follow-up data. This allows evidence-based guidance for surveillance intervals of 1 or 3 years for new technologies with limited longitudinal data.

Validation of the 2019 American Society of Colposcopy and Cervical Pathology Online Cervical Cancer Screening Program via 9 Large-Cohort Data of Chinese Women

Objective The aim of the study is to validate the applicability and performance of the 2019 US risk-based guideline for Chinese women. Materials and Methods The authors analyzed 10,055 cases with data on human papillomavirus testing, cytology, and pathologically confirmed diagnosis (analysis-set). According to the 2019 US risk-based guideline, the authors recorded the risk value and triage recommendations for each case. Then, they assessed the concordance of the guideline triage recommendations with pathology diagnosis for the relevant case from the real-world projects. Results Among the analysis-set, 9,495 cases with an estimated risk value were identified as analysis cohort while the remaining 560 cases were cataloged as “special cases.” Among the analysis cohort, 960 and 526 cases were pathologically confirmed as cervical intraepithelial neoplasia (CIN) 2+ and CIN3+, respectively. The US risk-based guideline recommended colposcopy or more aggressive interventions (Colp+) for 86.8% (833/960) of the CIN2+ and 95.8% (504/526) of the CIN3+ cases, with 87.1% sensitivity and 82.5% specificity for CIN3+ cases (AUC = 0.926, p < .0001). The US risk-based recommended no-Colp for 98.0% (6,142/6,269) of the pathologically confirmed CIN1 or benign cases. In addition, 97.3% (545/560) of the “special cases” cases were recommended as Colp+. Conclusions The 2019 US risk-based guideline works well with satisfied clinical sensitivity for CIN2+ and CIN3+ and seems applicable for cervical cancer screening in China.

Dynamic Spectral Imaging and Regular Colposcopy in CIN2+ Detection for HPV-Positive and/or Low-Grade Cytology Referrals

Objectives Dynamic Spectral Imaging colposcopy (DSI), an AI-driven technology, may improve cervical cancer diagnostics. This study aimed to evaluate the cervical intraepithelial neoplasia grade 2 or worse (CIN2+) sensitivity of DSI compared to regular colposcopy in individuals referred due to human papillomavirus (HPV)-positive and/or low-grade cytology. Methods This multicenter comparative cross-sectional study included individuals aged ≥18 years referred for colposcopy due to HPV positivity and/or low-grade cytology. Participants underwent either DSI or regular colposcopy. Colposcopists first identified the most suspicious area; in the DSI group, this was done before reviewing the DSI color map. The worst colored area was then selected, followed by additional biopsies. All participants had 4 cervical biopsies taken, with the most severe diagnosis as the gold standard. The primary outcome was CIN2+ detection sensitivity comparison between groups using a chi-square test. Results A total of 411 individuals underwent examination with DSI and 308 had regular colposcopy. The sensitivity for detecting CIN2+ with DSI was 69.3% (95% CI = 61.2–76.7) with an average of 1.3 biopsies, comparable to the sensitivity of the regular group when 2 biopsies were taken (68.3%, 95% CI = 58.3–77.2). No significant sensitivity differences were observed between groups when 3 or 4 biopsies were combined. Conclusion The DSI color map did not show a clinically significant improvement in CIN2+ detection sensitivity compared to regular colposcopy. However, multiple biopsies enhanced sensitivity and remained superior for CIN2+ detection in both colposcopy groups.

The Impact of COVID-19 Pandemic on Screening Programs for Cervical Cancer Prevention Across Europe

Objective The aim of the study was to estimate the impact of COVID-19 pandemic on the practice of cervical cancer screening in European countries. Materials and Methods A 3 rounds e-survey was conducted among the 31 European Federation for Colposcopy member countries during 2020. Each representative was asked to answer to each questionnaire for their own country. Questionnaires were not anonymous. The first questionnaire was sent in April 2020 and second and third in June and December 2020, respectively. Results Twenty five of the 31 European countries solicited responded. A total of 19 countries (70.4%) reported that screening for cervical cancer was suspended at least once during the 3 rounds of questionnaires. In addition, 11 countries reported stopping colposcopy and treatments for cervical precancerous lesions at least once during the 3 rounds of questionnaires. These situations evolved with time, with the highest rate of countries recommending suspension of screening, colposcopy, and treatments during the second round of the survey. At round 3, no country recommended screening, colposcopy, and treatment, and 12 countries (57.5%) reported normal screening was fully implemented. Conclusions Our results suggest massive disruption in cervical cancer screening programs across Europe resulting from COVID-19 pandemic. Increase in the incidence of cervical cancer is to be expected.

High Expression of Circular RNA–Mitochondrial tRNA Translation Optimization 1 Assists the Diagnosis of High-Risk Human Papillomavirus Infection in Cervical Cancer

Objective Persistence of high-risk human papillomavirus (HR-HPV) infection is a paramount determinant in cervical cancer (CC) development. Circular RNAs have the potential to be promising biomarkers for various cancers. This study explored circular RNA–mitochondrial tRNA translation optimization 1 (circMTO1) expression in the serum of CC patients and its clinical value in diagnosing CC and predicting HR-HPV infection. Materials and Methods In total, 125 CC patients (including 78 cases with HR-HPV) were enrolled, with another 76 healthy people as controls. Serum circMTO1 and miR-199a expressions were detected by reverse transcription–quantitative polymerase chain reaction, and the diagnostic efficacy of circMTO1 for CC and HR-HPV infection was analyzed by the receiver operating characteristic curve. According to the median of serum circMTO1 expression, CC patients were assigned into circMTO1 low/high expression groups to analyze the correlation between circMTO1 and clinical parameters using the Fisher and χ2 tests. Independent association of circMTO1 with HR-HPV infection in CC was evaluated via logistics multivariate regression analysis. Targeted relationship between miR-199a and circMTO1 was predicted by Starbase Web site and validated via dual-luciferase assay, with their correlation further assessed by Pearson analysis. Results Serum circMTO1 was increased in CC patients and prominently elevated in HR-HPV–positive CC patients, with a level greater than 1.485 assisting CC diagnosis and a level greater than 2.480 assisting HR-HPV–positive diagnosis. The circMTO1 was interrelated to clinical stage, tumor differentiation, lymph node metastasis, invasion depth, and independently linked with HR-HPV infection in CC. Serum miR-199a was downregulated in HR-HPV–positive CC patients and inversely correlated with circMTO1. Conclusions Serum circMTO1 is upregulated in HR-HPV–positive CC patients and has a diagnostic value for HR-HPV infection in CC.

Changes in Cervical Cytology Results and Human Papillomavirus Types Among Persons Screened for Cervical Cancer, 2007 and 2015–2017

Objectives Since 2006, the US human papillomavirus (HPV) vaccination program has led to decreases in HPV infections caused by high-risk vaccine-targeted HPV types (HPV 16/18). We assessed differences in high-risk HPV prevalence by cervical cytology result among 20- to 24-year-old persons participating in routine cervical cancer screening in 2015–2017 compared with 2007. Materials and Methods Residual routine cervical cancer screening specimens were collected from 20- to 24-year-old members of 2 integrated healthcare delivery systems as part of a cross-sectional study and were tested for 37 HPV types. Cytology results and vaccination status (≥1 dose) were extracted from medical records. Cytology categories were normal, atypical squamous cells of undefined significance, low-grade squamous intraepithelial lesions (SIL), or high-grade SIL/atypical squamous cells cannot exclude high-grade SIL. Prevalences of HPV categories (HPV 16/18, HPV 31/33/45/52/58, HPV 35/39/51/56/59/66/68) were estimated by cytology result for 2007 and 2015–2017. Results Specimens from 2007 (n = 4046) were from unvaccinated participants; 4574 of 8442 specimens (54.2%) from 2015–2017 were from vaccinated participants. Overall, HPV 16/18 positivity was lower in 2015–2017 compared with 2007 in all groups: high-grade SIL/atypical squamous cells cannot exclude high-grade SIL, 16.0% vs 69.2%; low-grade SIL, 5.4% vs 40.1%; atypical squamous cells of undefined significance, 5.0% vs 25.6%; and normal, 1.3% vs 8.1%. Human papillomavirus 31/33/45/52/58 prevalence was stable for all cytology groups; HPV 35/39/51/56/59/66/68 prevalence increased among low-grade SIL specimens (53.9% to 65.2%) but remained stable in other groups. Conclusions Prevalence of vaccine-targeted high-risk HPV types 16/18 was dramatically lower in 2015–2017 than 2007 across all cytology result groups while prevalence of other high-risk HPV types was mainly stable, supporting vaccine impact with no evidence of type replacement.

Contribution of Etiologic Cofactors to CIN3+ Risk Among Women With Human Papillomavirus–Positive Screening Test Results

Objective The US screening and management guidelines for cervical cancer are based on the absolute risk of precancer estimated from large clinical cohorts and trials. Given the widespread transition toward screening with human papillomavirus (HPV) testing, it is important to assess which additional factors to include in clinical risk assessment to optimize management of HPV-infected women. Materials and Methods We analyzed data from HPV-infected women, ages 30–65 years, in the National Cancer Institute–Kaiser Permanente Northern California Persistence and Progression study. We estimated the influence of HPV risk group, cytology result, and selected cofactors on immediate risk of cervical intraepithelial neoplasia grade 3 or higher (CIN 3+) among 16,094 HPV-positive women. Cofactors considered included, age, race/ethnicity, income, smoking, and hormonal contraceptive use. Results Human papillomavirus risk group and cytology test result were strongly correlated with CIN 3+ risk. After considering cytology and HPV risk group, other cofactors (age, race/ethnicity, income, smoking, and hormonal contraceptive use) had minimal impact on CIN 3+ risk and did not change recommended management based on accepted risk thresholds. We had insufficient data to assess the impact of long-duration heavy smoking, parity, history of sexually transmitted infection, or immunosuppression. Conclusions In our study at the Kaiser Permanente Northern California, the risk of CIN 3+ was determined mainly by HPV risk group and cytology results, with other cofactors having limited impact in adjusted analyses. This supports the use of HPV and cytology results in risk-based management guidelines.

Prognosis of Human Papillomavirus–Negative Compared to Human Papillomavirus–Positive Cervical Cancer

Objectives The aims of the study were to evaluate the prevalence and prognosis of human papillomavirus (HPV)-negative cervical cancer (CC) and to compare these to data for HPV-positive CC. Materials and Methods This retrospective cohort study compared between HPV-negative CC and HPV-positive CC patients. Primary end points were disease-free survival and overall survival. Secondary end points were demographic and clinical variables including histological diagnosis, stage, and treatment. Results Of 233 women with CC, 18 (8%) tested HPV-negative. During a median follow-up of 45 months, 33 (14%) recurrences and 41 (18%) deaths were observed. Eleven of the 18 women (61%) who tested HPV-negative and 41 of the 215 (19%) who tested HPV-positive had only adenocarcinoma (p < .001). In a multivariate logistic regression analysis, advanced age (p = .003) and primary treatment with chemotherapy and/or radiotherapy (p < .001) remained statistically significant for recurrence or mortality (disease-free survival). The factors associated with lower survival were advanced age (p = .008), higher stage at diagnosis (p < .001), and HPV negativity (p = .062). Median overall survival for HPV-positive CC was not reached, compared with 24 months for HPV-negative CC. Kaplan-Meier curves showed lower rates of disease-free survival (p = .008) and overall survival (p = .011), for women with HPV-negative compared with HPV-positive CC. Conclusions The relatively poor prognosis of HPV-negative CC is important in light of its relatively high prevalence, which could increase proportionally to HPV-positive CC due to increased HPV screening and vaccination. Further studies are needed to confirm whether HPV status is truly an independent prognostic factor in CC.

Self-Collected Swabs for Primary HPV Screening in an Underscreened Population in Hawaii

Objectives This study assessed the feasibility and acceptability of Human Papillomavirus (HPV) self-swab collection at a Hawaii-based Federally Qualified Health Center in the United States with low cervical cancer screening rates. Methods Patients with an indication for cervical cancer screening were approached during their scheduled primary care visit. Consenting participants self-collected a sample for primary HPV testing. After sample collection, participants completed a 5-minute written survey concerning their experience collecting the sample and knowledge of cervical cancer. Results From August 2023 through May 2024, 20 participants enrolled and completed the study, including 5 participants who had never undergone any prior cervical cancer screening and 7 participants over the age of 65. The HPV analysis confirmed 1 positive result. Most (17 of 20) of the participants described the self-collection process as very easy or easy. Knowledge of HPV and cervical cancer prevalence was low with only 2 of 20 participants (10%) correctly identifying the prevalence of these conditions. Conclusions Self-swab screening for HPV is feasible with high patient satisfaction in the studied population.

Improving Vulvar Self-examination Performance in a Population at Increased Risk of Vulvar Cancer

Objective The aim of the study was to evaluate whether a teaching session and optional reminders improved frequency of performance of vulvar self-examination (VSE) in a population at increased risk of vulvar cancer. Methods Participants were recruited from Colposcopy and Vulvar Dermatology clinics at a publicly funded academic hospital in Ontario, Canada. Participants completed a questionnaire, were taught how to perform a VSE, and were given an information booklet. They had the option to receive phone or electronic health record reminders to complete a VSE over the course of the next 6 weeks. After 6 weeks, participants were contacted to survey their VSE behaviors. Data were analyzed using descriptive statistics. Results Two hundred nineteen participants completed the study. Prior to the study, 28 participants (13%) had heard of VSE, while 31 (14%) had never looked at their external genitalia before. At a 6-week follow-up, 181 out of 219 participants (83%) completed a VSE, compared to 16% who regularly performed VSEs prior to the intervention ( p < .001). There was a statistically significant improvement in self-reported ability to find the labia minora, labia majora and urethra after the intervention. Conclusions Despite low baseline levels of familiarity with VSE, a simple teaching session, with or without reminders was associated with high performance of VSE in a population at increased risk of vulvar cancer.

General Versus Local Anesthesia in Loop Electrosurgical Excision Procedures: A Systematic Review and Meta-Analysis

Objective Loop electrosurgical excision (LEEP) is the standard of care for high-grade cervical intraepithelial neoplasia. The primary aim of this study was to compare patient-reported outcomes among patients who received local anesthesia (LA) during LEEP with those who received GA. Methods PubMed, Embase, and Cochrane databases were searched for studies comparing GA with LA in LEEP. Primary outcomes were postprocedure pain and satisfaction, including the likelihood of choosing the same anesthesia method again. Statistical analysis used Review Manager 5.4, heterogeneity was assessed with I 2, and a random-effects model was applied. Results Six studies (2,169 patients; 1,536 LA, 633 GA) met inclusion criteria. Postprocedure pain was slightly lower with GA than LA (standardized mean difference: −0.49, 95% CI = −1.88, 0.89), but this was not statistically significant. Satisfaction was higher for GA (odds ratio: 1.62; 95% CI = 0.94, 2.79), though not significantly. GA patients had larger cone volumes (mean difference: 0.46 cm3; 95% CI = 0.29, 0.62), and deeper excisions, though depth was not statistically significant (mean difference: 0.75 mm; 95% CI = −0.23, 1.74). Conclusions While GA was associated with minimally lower pain and greater satisfaction, these differences were not statistically or clinically meaningful. GA was also linked to larger cone volumes, potentially increasing risks for future pregnancies. Given the higher risks and costs of GA, LA may be preferable for LEEP.

Knowledge of the Human Papillomavirus Vaccine and Willingness to Accept Vaccination in the Postpartum Period

Objectives Human papillomavirus (HPV) vaccines prevent cervical cancer. The inpatient postpartum period presents a unique window for vaccination. The authors’ study investigates HPV vaccine knowledge, barriers to vaccination, and willingness to get vaccinated during inpatient postpartum care. Materials and Methods The authors conducted a cross-sectional survey of 147 participants, age 18 to 26, who delivered at the authors’ institution between November 1, 2019, and April 30, 2020. Participants completed a questionnaire that included demographics, vaccine knowledge, hesitancies, and willingness to vaccinate. The authors used descriptive statistics and compared groups with chi-square or Wilcoxon rank sum for categorical variables and t-test for continuous variables. Results Of the 147 patients, 58 (39.46%) were fully vaccinated against HPV and 89 (60.54%) of participants were unvaccinated or partially vaccinated. There was a greater proportion of African American and Asian participants among unvaccinated women (28.1% vs 20.7% and 16.9% vs 1.7%, respectively). Most unvaccinated participants (52.9%) were willing to get vaccinated in the postpartum unit. Both vaccinated and unvaccinated groups were similarly aware that the HPV vaccine prevents cervical and oropharyngeal cancers and genital warts. The top barrier to future vaccination was forgetting to complete the vaccination series. Conclusions Most women were not fully vaccinated but were willing to receive their first dose while in the postpartum unit. African American women were less likely to be vaccinated and expressed more unwillingness to accept vaccination. The authors identified barriers to HPV vaccination that can be tackled with the initiation of inpatient postpartum vaccination.

Lugol's Solution Reduces Positive Margins and Residual Disease After the Large Loop Excision of Transformation Zone

Objective This study aimed to examine whether the intraoperative use of Lugol's solution reduces the proportion of positive resection margins (RMs) using the data of women who underwent large loop excision of the transformation zone (LLETZ). Materials and Methods A total of 1,751 consecutive women with cervical intraepithelial neoplasia (CIN) who underwent LLETZ with or without Lugol's solution were retrospectively retrieved from each database of 3 university hospitals in South Korea. Outcomes included positive RMs and residual disease pathologically confirmed within 6 months after LLETZ. Results Positive RMs were noted in 345 cases (19.7%). Among 1,507 women followed up, residual disease was diagnosed in 100 cases (6.6%) (69/308 cases with positive RMs; 31/1,199 cases with negative RMs). The Lugol's solution group was less likely to have positive RMs (11.8% vs 25.5%, p < .01), to require additional surgical intervention (5.4% vs 10.2%, p < .01), and to have residual disease (4.9% vs 8.0%, p = .02). On multiple logistic regression analysis, Lugol's solution reduced the proportion of positive RMs (adjusted odds ratio [aOR], 0.31). Age (50 years or older; aOR, 1.64), preconization cervical cytology (aOR, 1.53), high-risk human papillomavirus (aOR, 1.75), and CIN 2 or 3 (aOR, 2.65) were independent risk factors for margin positivity (p < .01 for all except high-risk human papillomavirus of p = .05). Conclusions Lugol's solution optimizes CIN treatment by reducing the proportion of positive RMs and residual disease after LLETZ.

Cervical Cancer Prevention: Screening Among Undocumented Hispanic Women Compared With Documented Hispanic Women

Objective This study compared cervical cancer knowledge, screening practices, and barriers to screening among undocumented and documented Hispanic women. Materials and Methods An anonymous cross-sectional survey was administered to self-identifying Hispanic women older than 21 years at community-based clinics and health care–focused community sites in Rhode Island. The survey included demographics, immigration status, questions related to cervical cancer knowledge, screening practices, and barriers to screening. Participants were stratified based on their immigration status. Categorical variables were compared by χ2 or Fisher exact test. Knowledge scores and the number of barriers were compared by t test and Wilcoxon rank sum test, respectively. p values of less than .05 were considered statistically significant. Results Seventy-three undocumented women and 70 documented women were enrolled. Undocumented women had a significantly lower mean cervical cancer knowledge score (3.53, SD =1.97) compared with documented women (4.43, SD = 2.04; p = .0085) and also experienced more barriers to having cervical cytology or a human papillomavirus test (p = .001). Eighty-eight percent of the undocumented women and 47% of the documented women did not have health insurance (p < .0001). Sixty-two percent of the undocumented women felt that their lack of documentation was a barrier to cervical cancer screening. Fifty percent of the undocumented and 47% of the documented women had never heard of the human papillomavirus vaccine. Conclusions Undocumented women have significantly lower mean cervical cancer knowledge scores compared with documented women. A lack of legal documentation is a significant barrier to cervical cancer screening among Hispanic women. Challenges inherent to being undocumented may contribute to women's lower knowledge scores and more pronounced barriers.

Assessing Inequities in Cervical Cancer Quality of Care and Survival Related to Ethnicity and Socioeconomic Factors

Objective This study aimed to assess the effect that race and socioeconomic factors have on the provision of care to cervical cancer patients based on National Comprehensive Cancer Network (NCCN) recommended treatment guidelines. Materials and Methods To do this, we completed a retrospective cohort study using the American College of Surgeon's Nation Cancer Database from 2004 to 2016. We identified all reported cases of cervical cancer in that period. Two cohorts were created using self-reported racial demographic data, Hispanic- and White, non-Hispanic–identified patients. Our primary outcome variables were adherence to NCCN-recommended treatment and 5-year overall survival. Adherence to NCCN-recommended treatment was determined by the provision of surgical and/or radiation and/or chemotherapy treatment based on the clinical stage at time of diagnosis and the presence or absence of lymphovascular space invasion. We used bivariate analyses to compare baseline characteristics between the 2 cohorts, multivariable logistic regression to identify independent predictors of 5-year survival, and Cox proportional hazards models to compute survival by group. Results The difference in NCCN-adherent care between the 2 cohorts was found to be not statistically significant (p = .880). A log rank (Mantel-Cox) χ2 test showed that there was a statistically significant difference between the 2 groups in overall survival with the Hispanic-identified patients living longer (p < .001). Our study is limited by the effect large databases confer on finding statistical significance. Conclusions Hispanic-identified women with cervical cancer receive NCCN-compliant care and live longer than their White, non-Hispanic counterparts.

Time-Dependent Squamous Cell Carcinoma Antigen in Prediction of Relapse and Death of Patients With Cervical Cancer

Objective The aim of the study was to develop a methodology to identify the best use of a longitudinally measured biomarker in relevance to prognosis. Materials and Methods Data of squamous cell carcinoma antigen (SCC-Ag) from 770 patients with cervical squamous cell carcinoma (SCC) were used. The pretreatment, nadir, and time-dependent SCC-Ag values were analyzed in relevance to disease relapse and death with univariate and multivariate analysis side by side with a variety of available clinicopathologic factors. The predictive power of the significant variates was evaluated by C-index with 5-fold cross validation. Results The pretreatment, nadir, and time-dependent SCC-Ag were all significant risk factors for both relapse and death in the univariate analysis (p < .05), and the time-dependent SCC-Ag had the highest C-index in both events. The nadir and time-dependent SCC-Ag were both independently significant in response to relapse with International Federation of Gynecology and Obstetrics (FIGO) stage as the covariate, and the latter had a higher C-index (0.745). Only the time-dependent SCC-Ag was independently significant together with FIGO stage in response to death with the C-index at 0.844. Conclusions Increases in the serum level of SCC-Ag in cervical SCC patients suggest a higher risk of both relapse and death. The best use of serial SCC-Ag measurements is to include the time-dependent value in prognostic assessment with FIGO stage also accounted for. Cervical SCC patients should be followed up on their levels of SCC-Ag, and prognostic evaluation should be updated with recent measurements.

Off-Label Use of Imiquimod for Lower Female Genital Tract Diseases: A Systematic Review

Objectives Imiquimod (IMQ) is an immunomodulatory topical drug with antiviral and antitumoral activity. Given its effectiveness and safety, IMQ is broadly off-label used for many vulvovaginal conditions as monotherapy and in association with other therapeutic approaches. However, standardized dose regimens and the total duration of therapy are still debated. This review aimed to summarize the current evidence on off-label uses of IMQ in different vulvovaginal conditions and compare its effectiveness to other gold standard treatments. Methods The literature review used PubMed/MEDLINE and ClinicalTrial.gov as primary sources, including articles from January 2000 to June 2024. Results Overall, 105 articles were included, of which 26 articles on vulvar Paget disease, 36 articles on vulvar intraepithelial neoplasia, 20 articles on vaginal intraepithelial neoplasia, 6 articles on vulvovaginal melanoma, and 17 articles on other conditions (molluscum contagiosum, herpes simplex type II infection, plasma cell vulvitis, and candidiasis). Most treatments included IMQ as monotherapy, or in combination and/or in alternative to other approaches, such as surgery, laser, human papillomavirus vaccination, systemic therapies (antiviral drugs, steroids), local therapies (1% cidofovir, 5% 5-fluorouracil, photodynamic therapy), and observation. The most frequent dose regimen was 3 times/week for 12–16 weeks. Outcomes widely varied among different conditions. Conclusion Off-label topical IMQ represents a noninvasive and effective option for treating lower genital tract conditions as monotherapy or in association with other treatments. The IMQ therapy must be personalized based on physician and patient preference.

Treatment Interventions for Usual-Type Vulvar Intraepithelial Neoplasia: A Systematic Review and Meta-analysis

Objectives This study aimed to evaluate the efficacy of treatments for usual-type vulvar intraepithelial neoplasia (uVIN). Methods This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searching PubMed, Embase, Scopus, Web of Science, the Cochrane Central Register of Controlled Trials, PsycINFO, and Clinical Trial Databases in July 2024. Clinical trials comparing treatments for uVIN to a placebo or other treatments were included. The risk of bias was assessed using the Cochrane Risk of Bias (RoB 2.0) tool, and the strength of evidence was evaluated using the GRADE approach. Results Out of 10,306 studies, 8 met the inclusion criteria. A meta-analysis of 2 studies comparing imiquimod 5% to placebo found that 55.3% of women in the imiquimod group experienced total lesion resolution, compared to 0% in the placebo group (risk ratio = 18.21, 95% CI = 2.60–127.69). Cidofovir 1% had a complete response rate of 41%, while imiquimod 5% showed a 42% response. Imiquimod 5% was well-tolerated and showed a trend toward noninferiority to surgical treatments. Ultrasonic surgical aspiration is less scary than CO2 laser vaporization, with similar efficacy. Sinecatechins 10% showed lesion improvement in the best observed clinical response compared to those in the placebo group (p = .002), while indole-3-carbinol and Omiganan were ineffective despite adherence to treatment protocols. Conclusions Imiquimod 5% is an effective treatment for uVIN with comparable results to surgery. Cidofovir 1% is another effective option. Less invasive treatments are beneficial for multifocal or extensive lesions but combining medical and surgical approaches has not been studied.

High Risk of HPV-Related Preneoplastic and Neoplastic Vulvar Lesions in Women Living With HIV

Objective The authors aimed to investigate the epidemiology of human papilloma virus (HPV)-related preneoplastic and neoplastic vulvar lesions in a large cohort of women living with HIV (WLWH). Materials and Methods The authors retrospectively selected 1,796 WLWH who had a gynecological examination, cervical cytology, high-risk (HR-) HPV test, vulvoscopy, and colposcopy with targeted biopsies when necessary between 1987 and 2020 at 2 Italian institutions. Univariable and multivariable regression analyses were carried out to test the association of the anamnestic and clinical data with the development of precancerous and cancerous lesions. Results At baseline, 348 (19.4%) of 1,796 WLWH had genital warts, 30 (1.7%) had vulvar high-grade intraepithelial neoplasia (VHSIL), and 2 (0.1%) had squamous cell carcinoma of the vulva. Among 895 WLWH who had more than 1 year of follow-up, the authors found 40 (4.5%) new cases of VHSIL and 7 (0.8%) cases of vulvar cancer. The cumulative incidence of VHSIL and vulvar cancer was respectively 0.56 and 0.10 per 100 person-years. Risk factors independently associated with the development of vulvar HSIL and cancer included history of injection drug use (p < .01), genital warts at baseline (p < .001), HR-HPV test positivity at diagnosis (p < .001), and severe immunodepression (CD4 cell count <200 cells/mL) at diagnosis (p < .01). Conclusions WLWH are at high risk of vulvar high-grade intraepithelial neoplasia and cancer, especially those with severe immunodepression. A careful inspection of vulva, perineum and anus, possibly with the aid of colposcopy, should become part of the surveillance protocol of HIV-infected women.

Fat Grafting in Vulvar Lichen Sclerosus: Long Term Follow-Up

Objective The rationale for the use of autologous fat grafting in the treatment of vulvar lichen sclerosus (VLS) consists in reduction of inflammation, regeneration of tissues, volume increase, and pain fiber control. The main outcome of this study was the evaluation of patients' satisfaction after treatment. Secondary outcomes included modifications in symptoms, psychosexual wellbeing, vulvar hydration, and histology after surgery. Methods Eligible for this study were women aged 18–85 years with a histological diagnosis of VLS who underwent at least one autologous vulvar fat grafting at the authors’ center, between 2010 and 2019. In 2021, all women underwent a clinical reevaluation, comprehensive of vulvoscopy, vulvar biopsy, and handing out of validated questionnaires. Results Overall, 88.7% of patients declared themselves very satisfied/satisfied with the procedure. All symptoms were improved postsurgery; in particular, the difference was statistically significant for pruritus, burning, and dyspareunia (p < .05). Sexual function was also improved at time of reevaluation, as were depressive and anxiety symptoms (p < .05). No cases of vulvar intraepithelial neoplasia or cancer occurred during follow-up and vulvar architecture remained stable, although patients reported a significantly reduced need for topical steroids (p < .0001). Lastly, in postoperative biopsies, inflammatory infiltrate was stable or reduced, and the distribution of elastic fibers was comparable or restored in most patients. Conclusions Patient satisfaction with fat grafting is detectable up to 11 years after surgery, and as such, it may represent a valid therapeutic option in selected cases of VLS.

Prevaccine Human Papillomavirus Status in Invasive and Intraepithelial Lesions of the Vulva in New Zealand Women

Objective The human papillomavirus (HPV) vaccine, introduced in New Zealand (NZ) in 2008, is predicted to substantially lower the incidence of HPV-associated precancers and cancers. The aim of this study is to estimate the proportion of vulvar intraepithelial neoplasia (VIN) lesions and invasive vulvar squamous cell carcinomas (SCCV) attributable to HPV in NZ women treated by the Auckland Regional Gynecological Oncology Service, covering an estimated 50% of the NZ population. Materials and Methods Polymerase chain reaction and reverse hybridization were used to analyze retrospective histologically proven SCCV from 1990 to 2007 and VIN lesions from 2000 to 2007 for HPV content and genotype in a collaborative study with the Catalan Institute of Oncology. Immunohistochemistry for p16INK4a was performed on SCCV, which were attributed to HPV if both tested positive. Results Polymerase chain reaction testing for HPV content and genotype was performed on 66 VIN lesions (all high-grade squamous intraepithelial lesions) and 189 SCCV. In addition, p16 immunohistochemistry was performed on 168 of the 189 SCCV (88.9%) tested for HPV-DNA. Overall, 61 SCCV cases (36.3%) were attributed to HPV (HPV+/p16+), and 89 SCCV cases (53%) were considered to have developed independently of HPV (HPV−/p16−). Known high-risk HPV genotypes were present in 96.8% of HPV-DNA–positive vulvar high-grade squamous intraepithelial lesions and 98.4% of HPV-attributable SCCV. Human papillomavirus 16 represented the most common genotype in both. Conclusions Overall, the HPV vaccine is likely to substantially alter the profile of SCCV in our region. The results provide a baseline assessment of the HPV status of vulvar neoplasia before the introduction of the HPV vaccine.

Knowledge of Vulvar Anatomy and Self-examination in a Sample of Italian Women

Objective The aim of the study was to investigate the knowledge of vulvar anatomy and vulvar self-examination (VSE) in a sample of Italian women attending a gynecology clinic. Methods For this original research from May to July 2019, 512 women attending the Lower Genital Tract Clinic at the Department of Surgical Sciences of the University of Torino were invited to participate in a 29-question survey about vulvar anatomy, VSE, and sociodemographic details. Data were analyzed using descriptive statistics. Results Of 512 patients, 500 completed the questionnaire (98% response rate). The mean age of respondents was 41 years (range = 17–77 years). Education level was evenly distributed between elementary, high school, and university graduates. Only 15% of interviewed women were able correctly sketching vulvar anatomy. Seventy-six percent of the women had not heard about VSE, and 61% of the women approach their genitalia with feelings of shame and embarrassment. Only 23% of the women would seek medical advice after identification of possible abnormalities during VSE. A majority (69%) of the women would like to have more information about VSE and vulvar health through educational videos and social media. Conclusions Education about VSE may lead to earlier diagnosis of vulvar cancers and other pathologies. Further efforts are needed to disperse information about normal external female genital anatomy and VSE to achieve self-confidence among women.

Impact of Screening Modality on the Detection of Cervical Adenocarcinoma In Situ and Adenocarcinoma

Objective The aim of the study was to determine the impact of screening modality on the detection of cervical adenocarcinoma in situ (AIS) and adenocarcinoma. Materials and Methods This was a cross-sectional study of patients with AIS or adenocarcinoma who had undergone routine screening with cytology and high-risk human papillomavirus (HPV) cotesting between January 2007 and December 2017. Patients were stratified into 3 groups by screening test results: (1) HPV positive with abnormal cytology (HPV+/Pap+), (2) HPV negative with abnormal cytology (HPV−/Pap+), and (3) HPV positive with normal cytology (HPV+/Pap−). Demographic and clinical characteristics were collected. Data were analyzed with χ2, Fisher exact tests, and t tests as appropriate. Results Of the 118 patients diagnosed with AIS (n = 97) or adenocarcinoma (n = 21) after abnormal screening tests, 92 (78%) were detected by HPV+/Pap+, 15 (12.7%) were HPV+/Pap−, and 11 (9.3%) were HPV−/Pap+. Demographics were similar between groups, although the HPV+/Pap− patients had higher body mass indices. Rates of definitive hysterectomy were similar between groups (53.3%–80.0%, p = .11). Conclusions In our cohort, a significant proportion of AIS and adenocarcinoma was detected by both HPV alone (with normal cytology) and cytology alone (with negative HPV), suggesting that cotesting with both HPV and cytology may be a more sensitive method of detection of AIS and adenocarcinoma.

Addressing Unmet Basic Needs to Improve Colposcopy Adherence Among Women With Abnormal Cervical Cancer Screening

Objectives The aims of the study were to identify unmet basic needs (BNs) among women referred to colposcopy, to assess patient acceptability/satisfaction with assistance from a navigator to address unmet BNs, and to estimate adherence to colposcopy. Methods Women were recruited between September 2017 and January 2019 from 2 academic colposcopy centers, one serving a rural and one an urban area. Basic needs were assessed by phone before colposcopy appointments and considered unmet if unlikely to resolve in 1 month. Colposcopy adherence prestudy and poststudy implementation was abstracted over 4–6 months from administrative records. After a lead-in phase of 25 patients at each site, a BN navigator was offered to new participants with 1 or more unmet BNs. Primary outcome was adherence to initial appointment. Results Among 100 women, 59% had 1 or more unmet BNs, with similar prevalence between urban and rural sites. Adherence to initial colposcopy was 83% overall, 72% at the rural clinic, and 94% at the urban clinic (p = .006). These adherence rates were improved from 4 months before study launch (30/59 [51%] rural clinic and 68/137 [50%] urban clinic). Although acceptability of BN navigation was greater than 96% and women felt that it helped them get to their colposcopy visit, having a navigator was not associated with adherence. Women reporting no unmet BNs had the lowest adherence compared with women with 1 or more unmet BNs, regardless of navigator assistance (p = .03). Conclusions Disadvantaged women who need colposcopy have unmet BNs and value navigator assistance for initial appointments. However, when appointment scheduling includes telephone reminders and inquiring about BNs, a navigator may not add value.

Cervical Intraepithelial Neoplasia 3 (Cervical Intraepithelial Neoplasia 3/High-Grade Squamous Intraepithelial Lesion) in Human Papillomavirus–Vaccinated Women—Results From a Tertiary Referral Center

Objective High-grade cervical intraepithelial neoplasia (CIN 3) still develops in some vaccinated women despite established effectiveness of prophylactic human papillomavirus (HPV) vaccination. The purpose of this study was to define characteristics of women with CIN 3 after HPV vaccination referred to a gynecological dysplasia unit. Materials and Methods Retrospective analysis of HPV-vaccinated women with CIN 3 in a single German center. Between July 2018 and September 2020, 791 women were referred to our university hospital–based dysplasia unit for colposcopic evaluation of abnormal cytological findings. Human papillomavirus vaccination status was retrieved. Human papillomavirus typing was performed in lesional biopsies and cervical swabs. Results Nine women were identified who had previously been vaccinated with the quadrivalent HPV vaccine (Q-HPV) and were diagnosed with histologically confirmed CIN 3/high-grade squamous intraepithelial lesion. The Q-HPV had been administered between 12 and 28 years of age and 1–13 years before CIN 3 diagnosis. Nine different high-risk (HR)-HPV types were found in the CIN 3 biopsies, 6 monoinfections (twice HPV 16, once HPV 18, HPV 31, HPV 52, HPV 58, respectively) and 3 dual infections (HPV 33 + 52, HPV 51 + 52, HPV 53 + 66). Seven of these 9 HR-HPV types are not covered by Q-HPV, but only 2 CIN 3 lesions carried HR-HPV types not included in the nonavalent HPV vaccine. Conclusions It is important to implement vaccination recommendations and administer HPV vaccination as early as possible in HPV-naive individuals. Because not all HR-HPV types are covered by the available HPV vaccines, other types may still cause CIN 3/high-grade squamous intraepithelial lesion. This requires further screening after vaccination, especially in women who were previously vaccinated with the bivalent or the quadrivalent HPV vaccine.

Accuracy of HPV Testing Using Self-collected Urine Compared With Physician-collected Cervical Specimen for HSIL or Worse

Objectives: Self-collection is a strategy to facilitate HPV testing with the objective of eliminating cervical cancer, as set by the World Health Organization for completion by 2030. Using urine samples for HPV testing offers the advantages of being noninvasive and eliminating barriers to screening. However, concerns remain regarding its accuracy. Therefore, the meta-analysis focused on verifying the comparative effectiveness of HPV testing using self-collected urine specimens versus physician-collected cervical specimens. Methods: A search of PubMed, Embase, and the Cochrane Library databases was conducted to identify studies of HPV testing. The studies incorporated within the current meta-analysis evaluated the diagnostic accuracy of HPV testing for high-grade squamous intraepithelial lesion or worse (HSIL+) with self-collected urine specimens in comparison with physician-collected cervical specimens. Furthermore, studies that offered explicit data to facilitate meta-analysis were also included. The meta-analysis was conducted using a bivariate random-effects model. Results: A total of 23 articles were identified, including 8,332 self-collected urine and 8,324 physician-collected cervical samples. The meta-analysis yielded a pooled sensitivity of 84.5% of HPV testing with self-collected urine specimens, and another meta-analysis yielded a pooled sensitivity of 92.1% of HPV testing with physician-collected cervical specimens for HSIL+. The subgroup analysis revealed that first-void urine with Colli-Pee for evaluating HPV testing reported a pooled sensitivity of 87.8%. Conclusions: HPV testing with physician-collected cervical specimens achieves higher sensitivity for detecting HSIL+ compared with self-collected urine. First-void urine, using a standard collection device, may yield a marginally elevated level of sensitivity.

Clinician Characteristics Associated With Adoption of Updated National Colposcopy Guidelines

Objective To evaluate adherence to the 2019 ASCCP risk-based management consensus guidelines for management of patients following colpscopic cervical biopsy among US colposcopists. Methods To elucidate factors associated with utilization of the 2019 guidelines for patients undergoing colposcopic cervical biopsy, the authors cross-sectionally surveyed physicians and advanced practice professionals who perform colposcopy. Clinicians responded to clinical vignettes describing scenarios for which management recommendations differed between 2019 and prior management guidelines. Vignette 1 involved deferral of repeat colposcopy for patients with a low-risk biopsy, HPV, and cytology results. Vignette 2 involved deferral of excisional treatment on a patient with repeated low-grade biopsy results. Binomial logistic regression models determined factors associated with utilization of 2019 guidelines. Results A total of 670 colposcopists participated from across the United States. For Vignettes 1 and 2, guideline-adherent responses were given by 30.5% and 66.1% of participants, respectively. Colpsocopists practicing in community health centers were more likely to perform guideline-concordant care for Vignettes 1 and 2. Hispanic compared to non-Hispanic colposcopists and Internal or Family medicine compared to OB-GYN colposcopists are less likely to perform guideline-concordant care in Vignette 2. Irrespective of their chosen response, most believed they were guideline-adherent. Conclusions Many colposcopists may not realize their current management strategies are inconsistent with 2019 guidelines. Tailored education initiatives could address knowledge gaps, maximize patient benefits, and minimize harms.

Role of Self-Sampling Devices for HPV Detection in Cervical Cancer Screening: A Systematic Review

Objectives: The aim of this study is to evaluate self-sampling devices as an innovative resource with high performance, acceptability, and implementation for improving Human Papillomavirus detection in cervical cancer screening. Methods: This systematic review followed PRISMA 2020 guidelines and counts with the PROPERO register. A comprehensive literature search was conducted following the PRISMA guidelines using PubMed, EBSCO, and Scielo databases, including articles published between 2014 and 2025 in English and Spanish. MeSH terms related to “Uterine Cervical Neoplasms,” “Papillomaviridae,” “Molecular Diagnostic Techniques,” and “Self-Testing” were used. Inclusion criteria included clinical trials and comparative studies evaluating self-sampling test performance in terms of sensitivity and specificity values. Exclusion criteria included studies without statistical analysis, duplicates, and test usage with no cervical cancer objective. Results: Seven eligible studies were included. Self-sampling devices, such as a brush-based device, swab-type device, and sponge-type swabs, demonstrated high acceptability and usability among women, especially in underserved populations. Sensitivity and specificity range oscillated between 75%-91% and 34%-74% respectively, depending on the device and reference method. Compared with clinician-collected samples, most self-collected tests showed comparable diagnostic accuracy, making them a viable option for early detection. Limitations included small sample sizes, heterogeneity in test platforms, and a lack of long-term outcomes. Conclusions: Self-sampling devices offer an important potential to reduce cervical cancer morbidity and mortality globally, particularly in limited-access health care services. Their implementation in routine women’s care and health screening contributes to reducing morbidity and mortality from cervical cancer. Further studies are needed to confirm long-term effectiveness and standardized implementation protocols.

The Effect of Cervical Blockade in LEEP Procedures Performed Under General Anesthesia: A Randomized Controlled Trial

Objective: To compare the effectiveness of pain and bleeding control between general anesthesia alone and general anesthesia combined with cervical blockade during the loop electrosurgical excision procedure (LEEP). Methods: This prospective, randomized, controlled, open-label, exploratory clinical trial included 40 patients diagnosed with high-grade squamous intraepithelial lesion (HSIL) by colposcopic biopsy. Patients were randomly assigned in a 1:1 ratio: the control group underwent LEEP under general anesthesia only (n = 20), and the study group received general anesthesia with additional local cervical anesthesia (n = 20). Intraoperative bleeding, pain scores, pathological specimen size, surgical margins, and postoperative complications were compared. Results: Demographic data were similarly distributed. Smoking was significantly more prevalent in the control group ( p <.01). Preoperative cervical cytology, HPV DNA results, colposcopic biopsy results, and hemoglobin values were also comparable between the groups. Postoperative hemoglobin values, hemoglobin decrease, specimen size, surgical margin status, or hospital admissions after discharge were similar ( p >.05). However, postoperative pain scores and intraoperative sponge usage were significantly lower in the cervical blockade group ( p <.01). Subgroup analyses showed that smoking had no effect on bleeding rates as well as specimen sizes, which also did not affect bleeding rates and pain scores ( p >.05). Conclusions: Cervical blockade in LEEP performed under general anesthesia significantly reduces bleeding and pain. It does not influence blood transfusions, recovery, hospital readmissions or complications. Cervical blockade may enhance patient comfort and minimize intraoperative morbidity during LEEP. These preliminary findings require confirmation in larger, multicenter, preferably blinded trials.

Conservative Management of CIN2 Within Primary HPV Cervical Cancer Screening Programme: A Cohort Study

Objectives: To quantify the probabilities of becoming HPV-negative, or receiving delayed treatment within 24 months in women with CIN2 managed conservatively; describing the determinants of the decision for conservative management, losses to follow-up and outcomes. Methods: This prospective cohort included biopsy-confirmed CIN2 from HPV-based pilot screening in Valcamonica, Italy. Women aged 45 and under, with no glandular lesion, and assessed as low-risk by gynecologists were offered conservative management instead of treatment; those who accepted were followed with HPV testing, cytology, and colposcopy at 6, 12, and 24 months; then, if the lesion persisted, treatment was recommended; a few women without inclusion criteria entered the conservative management protocol. Competing-risk models were built to investigate the determinants of testing negative and log-binomial models for the determinants of decision for conservative management and loss to follow-up. Results: In all, 180 out of 352 women with CIN2 choose conservative management. Within 24 months, 25 women were lost to follow-up. Of the remaining, 40.6% (95% CI: 32.8%-48.8%) tested HPV-negative, 43.9% (95% CI: 35.9%-52.1%) underwent delayed treatment, and 15.5% (95% CI: 10.2%-22.2%) remained HPV-positive. Younger age, immediate colposcopy referral, low-grade cytological and grade I colposcopy were associated with the conservative management decision. Women who had attended prior screening testing HPV-negative were more likely to become HPV-negative [SHR 1.93 (95% CI: 1.06-3.49)] and had better adherence to follow-up tests. Two cases of invasive carcinoma were identified in treated women. Conclusions: After 24 months, 40% of the women avoided treatment. Women diagnosed at the second HPV screening round are more suitable candidates for conservative management.

Use of Virtual Reality for Pain Relief During Cervical Conization Under Local Anesthesia: A Randomized Controlled Trial

Objectives Cervical conization (loop electrosurgical excision procedure) under local anesthesia is often associated with anxiety and procedural pain. Virtual reality (VR) glasses may enhance patient experience and reduce discomfort during medical interventions. The authors aimed to prospectively and randomly evaluate whether VR use during loop electrosurgical excision procedure may impact reported pain and anxiety. Methods In this randomized controlled study, women undergoing conization under local anesthesia were assigned to either a control group (no VR) or a study group using VR glasses during the procedure. Demographics, baseline anxiety levels, anticipated pain, intraprocedural pain, heart rate, patient satisfaction, and surgeon-reported procedural difficulty were compared between groups. Anticipated and actual pain was assessed using a 0–10 visual analog scale. Results A total of 67 women were randomized. Groups were comparable in age, body mass index, pathology, and anticipated pain (median 5.0 vs. 6.0, p = .667). No significant difference was found between groups in pain experienced during the procedure (median 3.0 vs. 2.0, p = .318), discomfort, anxiety, or heart rate. Experienced pain was significantly lower than anticipated in both groups ( p < .001). Patient satisfaction was high in both groups, 90% of patients who used VR would recommend it to others. Adverse effects related to VR were rare. Conclusions While the use of VR glasses did not reduce perceived pain compared to standard care, it was safe and associated with high patient satisfaction. Most women overestimated the pain they would experience during conization. Integrating VR technology may improve overall patient experience during cervical conization, even if it does not alter pain perception.

Follow-up of Women Testing Positive for Human Papillomavirus Non-16/18 With Normal Cytology in a Screening Context

Objective The aim of the study was to evaluate the risk for cervical intraepithelial neoplasia II (CIN 2) or worse associated with high-risk (HR) non-16/18 human papillomavirus (HPV) types among women with normal cytology in a screening context. Methods This population-based historical cohort study was conducted in a large state-mandate health provider. Human papillomavirus genotyping was performed on Pap tests collected in women that were positive for non-16/18 HPV types from 2019 to 2023. HPV detection was performed using COBAS (4800/6800) (Roche Diagnostics) test: a qualitative in vitro test for the detection of 14 HR HPV types. The women were followed for histopathologic outcomes until end of 2024. Cumulative incidence proportions of CIN 1, 2, and 3 or worse were calculated. Results Of 24,439 women tested positive for HPV during the study period, a total of 7,930 women tested positive for HR HPV non-16/18 with a normal cytology. Among these, 875 (11.1%) developed pathological findings in biopsy including CIN II ( n = 68, 0.9%) and CIN III ( n = 802, 10.1%) lesions, cervical squamous cell carcinoma and adenocarcinoma (4, 0.1%), as well as one case of adenocarcinoma in situ (0.01%). Conclusions Women with HR HPV non-16/18 and normal cytology represent a high-risk group requiring long-term follow-up. No malignancies were observed in the first year of follow-up, supporting the recommendation for retesting after 12 months and colposcopy referral if the infection persists.

Expertise in Gynecological Pathology Impacts Diagnosis of Atypical Glandular Cell Category in Cervical Cytology

Objectives The Pap test is effective for detecting squamous neoplasia, but the interpretation of atypical glandular cell (AGC) remains challenging because of its rarity, complex cytologic features, and interobserver variability. Although AGC represents a small proportion of Pap test diagnoses, it often leads to extensive follow-up. This study aimed to assess whether gynecologic pathology expertise improves diagnostic accuracy and reduces unnecessary interventions in AGC interpretation. Methods A retrospective review of AGC cases diagnosed between 2014 and 2024 at the authors’ institution was conducted. Among 107,615 Pap smears, 301 (0.28%) were initially classified as AGC. Of these, 221 had slides available for review, and 184 had adequate histologic follow-up. Cases were re-evaluated by a cytopathologist with additional gynecologic pathology training, blinded to clinical information, and reclassified according to the Bethesda System. Results Reclassification identified 62 cases as AGC, 1 as adenocarcinoma in situ, and 4 as adenocarcinoma. The remaining 117 cases were reassigned to other diagnostic categories. The malignancy rate increased from 39.1% to 53.9%, and the positive predictive value for significant histologic findings was 59.7%. Cytology-histology concordance improved from 26.6% to 64.1% (p = .002). Conclusions Gynecologic pathology expertise enhanced the diagnostic accuracy of AGC, improved malignancy detection, and significantly increased cytohistologic correlation. While decreasing sensitivity, it increases positive predictive value of AGC interpretation. These findings highlight the value of specialized training and the need for a specific, criteria-based approach to minimize unnecessary follow-up and optimize patient care.

How Does Transitioning to Primary Human Papillomavirus Screening Impact Colposcopy Services? Lessons From an Australian National Program

Objective In 2017, Australian's National Cervical Screening Program changed from 2-yearly cytology to 5-yearly primary human papillomavirus (HPV) testing. The Stakeholder Opinions of Renewal Implementation and Experiences Study (STORIES) aimed to capture stakeholder perspectives during implementation of the renewed National Cervical Screening Program. Materials and Methods Qualitative semistructured interviews were conducted with key National Cervical Screening Program stakeholders 11–20 months following the change, either face-to-face, online, or via phone. Data related to colposcopy services were thematically analyzed using Proctor's conceptual framework for implementation outcomes. Results We identified 4 overarching themes: non-adherence to guidelines, lack of preparedness, unintended consequences, and mitigation strategies. While an initial increase in colposcopy referral was expected following transition, many stakeholders found increased referrals to be inequitably spread across services and exacerbated by confusion about, or overuse of testing for, symptoms. Conclusions The study provides the first assessment of stakeholder perceptions and experiences relating to colposcopy services during a transition from cytology to HPV screening. Significant preparation is required to ensure equitable and timely access to colposcopy when transitioning cervical screening programs, including wide stakeholder communication to build confidence; clear guidelines, especially around symptoms; and adequate resourcing for colposcopy services to meet projected referral rates.

Risk of High-Grade Cervical Dysplasia in Older Patients With a Positive Human Papilloma Virus Cervical Screening Test

Introduction The Australian National Cervical Screening Program has mandated management algorithms that are uniform across all age groups, but evidence is emerging that perhaps the risk of high-grade squamous intraepithelial lesion (HSIL) may decrease in the postmenopausal period. Objective The aim of the study is to identify if patients ≥50 years of age referred to a tertiary colposcopy service have a different risk of HSIL or greater (+). Materials and Methods This is a retrospective cohort study of 3239 referrals to a hospital colposcopy clinic with a positive human papillomavirus (HPV) cervical screening test between December 2017 and May 2023. Patients were included if they were aged 25–74 years, had a cervix, and completed an outpatient colposcopic assessment. Medical records were analyzed to determine the incidence of HSIL+ for each age group and compared them using χ2 and multivariable regression. Results The overall incidence of invasive carcinoma was 0.93% and HSIL/adenocarcinoma-in-situ was 20.38%. Patients ≥50 years of age were less likely to have HSIL or greater diagnosed than those <30 (p < .0001) or those 30–49 (p < .0001), even after considering referral HPV subtype and reflex cytology (OR = 0.45, 95% CI = 0.34–0.59). The risk of invasive carcinoma in those aged ≥50 was no different than those aged 30–49 (p = .982). Conclusions We observed a lower incidence of HSIL or greater with increasing age even after considering referral HPV subtype and reflex cytology. As further data emerges regarding the risk of high-grade disease in those ≥50 years of age, refinement of the risk-based screening algorithm to account for advanced age may be required.

Endocervical Brush Cytology After Cervical Conization as a Predictor of Treatment Failure: A Prospective Cohort Study

Objective Endocervical curettage (ECC) is the gold standard for predicting the persistence of high-grade squamous intraepithelial lesions (HSIL) after cervical conization. However, ECC has a high rate of unsatisfactory samples and may be uncomfortable for women. Endocervical sampling with brush (ECB) has been proposed as an alternative to ECC, which, in addition to the cytological evaluation, allows performing HPV testing using the same sample. We compared ECC and ECB performed immediately after conization to identify women with persistent HSIL. Materials and Methods This is a prospective single-center study, including 518 patients who underwent conization over a 10-year period (2012–2021). Immediately after treatment conization, we performed ECB sampling followed by ECC to all patients. We evaluated the accuracy of the 2 techniques for diagnosing persistent HSIL during follow-up. Results Persistent HSIL was identified in 8.9% of women. Eighteen percent of the ECC samples and only 7% of ECB cytology were unsatisfactory (p < .001). The accuracy of detecting persistent HSIL was similar for ECB and ECC (89.0%, 95% CI = 85.9–91.5 vs 90.8%, 95% CI = 87.7–93.2; p = .797). Adding HPV testing to ECB cytological evaluation increased the accuracy to 91.5% (95% CI = 88.8–93.6). Conclusions ECB can be reliably used to identify women with persistent HSIL after conization, as its accuracy is similar to ECC, with a lower rate of unsatisfactory results. The technique allows adding HPV testing to cytological evaluation, improving the accuracy of the test.

Cross-Sectional Study on the Detection of HPV Infections for Cervical Cancer Screening Using a Self-Sampling Device

Objectives This study evaluates a new vaginal self-sampling device for high-risk human papillomavirus (HR-HPV) detection compared to clinician-collected samples using real-time polymerase chain reaction (PCR). Methods A total of 345 women aged between 23 and 72 were enrolled in this study. After receiving information about the study, women were provided with a vaginal collecting device to collect self-sample, and then a medical professional collected the cervical sample. All the clinician-collected samples were processed using the Cobas 4800 HPV assay, and the self-samples were processed with the automated MAIS extraction system. These results were used to compare the new device's performance to the clinician-collected cervical samples. All the clinician-collected samples were also analyzed with a new HPV screening assay to compare the performance of this assay on 2 different types of samples. Results Overall agreement for detecting any HR-HPV between clinician-collected samples and self-samples was 93.7% with a Cohen κ coefficient of 0.842. As both assays allow to identify genotypes 16, 18 and to detect the same 12 HR-HPV genotypes in a pool, the authors analyzed the agreement between self- and clinician-collected samples by genotypes and it was shown to be also excellent for HPV16 and the pool of other HR-HPV. Conclusions This self-sampling device has demonstrated detection rates that are comparable to those of samples collected by clinicians.

A Mixed-Methods Study Examining Guideline-Concordant Colposcopy Practices Among a National Cohort of US Colposcopists

Objectives The 2017 ASCCP Colposcopy Standards guidelines were designed to maximize the diagnostic yield of colposcopy. However, guideline adoption is often slow, and few studies have examined management of patients undergoing colposcopy. Methods To elucidate factors associated with utilization of the 2017 ASCCP Colposcopy Standards guidelines for patients undergoing colposcopic cervical biopsy, the authors cross-sectionally surveyed and interviewed physicians and advanced practice providers who perform colposcopy. Clinicians responded to a clinical vignette describing a common colposcopy scenario. Clinicians were asked to describe where they would biopsy and why. Binomial logistic regression models determined factors associated with guideline concordance. Qualitative interviews further explored practice patterns. Results A total of 671 colposcopists participated from across the United States. A total of 541 (81%) participants reported colposcopy practice concordant with the 2017 ASCCP Colposcopy Standards guidelines. A total of 490 (73%) participants reported that they were using the 2017 ASCCP Colposcopy Standards guidelines. Male colposcopists and those who were internal and family medicine clinicians were less likely to report guideline-concordant management than females and obstetrician-gynecologists. Colposcopists discussed the rationale behind guideline-concordant aspects of care, including taking targeted biopsies and using excisional rather than ablation procedures. Conclusions Most colposcopists perform biopsies and treatment consistent with the 2017 ASCCP Colposcopy Standards guidelines and understand the rationale behind multiple targeted biopsies.

Bridging Gaps in Cervical Cancer Care: A Web-Based Intervention to Improve Knowledge and Follow-up

Objectives Contributors to disparities and worse cervical cancer outcomes include limited education and loss to follow-up after an abnormal Pap smear. Effective interventions are necessary to engage diverse populations. The authors piloted an intervention to assess acceptability, knowledge uptake, and follow-up. Materials and Methods This prospective pilot study recruited patients scheduled for colposcopy visits at a government-insured clinic and faculty clinics within an academic medical center to use the Patient Activated Learning System (PALS). The PALS intervention included 5 short educational videos about human papillomavirus and colposcopy. Participants completed a baseline knowledge questionnaire, viewed PALS videos followed by post-intervention knowledge and acceptability surveys. Perceptions of PALS, anxiety, and impact on follow-up were evaluated. Results Of 63 (70%) participants completing the intervention, 24 (38%) were from the government-insured clinic and 39 (62%) from faculty clinics. Median age was 36 (range 30–48), 38 (63%) were racial and ethnic minorities, and 21 (33%) were non-Hispanic White. The intervention improved knowledge scores for the entire cohort (60%–75%, p < .01), even when stratified by race/ethnicity (p < .01 for all), income (p < .01), education (p < .01), practice (p < .01), and insurance type (p < .001). Participants found PALS convenient to use (4.6/5), enjoyable (4.2/5), and acceptable (4.6/5); 75% said the videos alleviated colposcopy-related anxiety, and 84% indicated PALS made them more likely to follow up. The guideline concordant follow-up rate among study completers was 73%. Conclusion In this pilot study, PALS was effective and acceptable among a diverse cohort. These free, widely viewed videos can successfully engage diverse populations to improve colposcopy knowledge and follow-up.

Trends in Cervical and Anal Cancer Incidence and Mortality in the United States

Objectives This article describe trends in the incidence and mortality of cervical (CC) and anal (AC) cancers by race and neighborhood socioeconomic status. Methods The Surveillance, Epidemiology, and End Results (SEER) database was used to construct a cohort of CC and AC cases from 2006 to 2018. Incidence rates and survival were calculated by race and neighborhood socioeconomic status (nSES). Annual percent change (APC) in incidence was calculated using linear regression, and 5-year overall survival (OS) by the Kaplan-Meier method. Results Of the cases, 33,487 CC and 16,018 AC cases were identified. Women of low nSES were nearly 4 times more likely to be diagnosed with cervical cancer than those of high nSES. Cervical cancer incidence declined marginally in all groups except for low nSES women who are White (APC 0.0). Women who are Black had lower 5-year OS than their nSES counterparts of other races (most notably for Black women of low nSES 53% vs White 63%). Similarly, the low nSES AC cohort contained nearly 3 times the number of diagnoses as the high nSES cohort. AC incidence increased most in women who are White (APC 1.8 and 2.2 for low and high nSES) and men who are Black and low nSES (APC 3.3). Five-year OS was lowest for men who are Asian American and Pacific Islander (40% and 50% for low and high nSES, respectively). Conclusions These data suggest a strong correlation between nSES, race, and their interaction on the incidence and survival trends of HPV-related disease and highlight inconsistent effects between cervical and anal cancers.

Hemostatic Efficacy of TachoSil in Loop Electrosurgical Excisional Procedure: A Prospective Randomized Controlled Study

Objective The aim of the study was to evaluate the hemostatic efficacy of the fibrin sealant patch (TachoSil) after loop electrosurgical excision (LEEP) and its influence on other complications and quality of life (QoL). Materials and Methods This single-blind, prospective, randomized study involved patients undergoing LEEP with or without TachoSil (1:1) between August 2014 and August 2015 in Asan Medical Center, Korea. Primary outcome measures were bleeding duration and the frequency of additional treatment owing to vaginal bleeding within 2 weeks after LEEP. Secondary outcome measures were vaginal bleeding volume using pictorial blood loss assessment chart (PBAC) score, the amount of vaginal discharge, the frequency of external genitalia, vaginal, and cervical infections within 2 weeks after LEEP, and changes in QoL. Results Of the 140 patients enrolled, 126 (90.0%) were successfully followed up and analyzed. The median vaginal bleeding duration and frequency of additional treatment owing to vaginal bleeding showed no significant difference in the TachoSil applied and nonapplied groups (p = .96 and p = .61, respectively). In addition, no significant difference was also observed in vaginal bleeding volume between 2 groups (p = .64). In subgroup analysis for patients who underwent large LEEP (the longest dimension of ≥2 cm), significant improvement was observed at physical functioning in QoL at 2–3 (p = .03) and 6 weeks (p = .03) after LEEP of the TachoSil applied group, compared to the nonapplied group. Conclusions TachoSil did not demonstrate significant hemostatic efficacy after LEEP. However, TachoSil improved patient recognition on physical function in patients who underwent large LEEP.

2019 ASCCP Risk-Based Management Consensus Guidelines: Updates Through 2023

Abstract This Research Letter summarizes all updates to the 2019 Guidelines through September 2023, including: endorsement of the 2021 Opportunistic Infections guidelines for HIV+ or immunosuppressed patients; clarification of use of human papillomavirus testing alone for patients undergoing observation for cervical intraepithelial neoplasia 2; revision of unsatisfactory cytology management; clarification that 2012 guidelines should be followed for patients aged 25 years and older screened with cytology only; management of patients for whom colposcopy was recommended but not completed; clarification that after treatment for cervical intraepithelial neoplasia 2+, 3 negative human papillomavirus tests or cotests at 6, 18, and 30 months are recommended before the patient can return to a 3-year testing interval; and clarification of postcolposcopy management of minimally abnormal results.

Updated Review for Guidelines for Cervical Cancer Screening in Immunosuppressed Women Without HIV Infection

Objective The purpose of this review was to examine new evidence since the authors' 2019 guidelines for cervical cancer (CC) screening in non-HIV immunocompromised persons and to provide updated recommendations based on literature review and expert opinion. In addition, human papillomavirus (HPV) vaccine efficacy in these populations was reviewed. Methods A literature search was performed similar to the authors' previous publication but was conducted through March 2023. Risk of CC, squamous intraepithelial lesions, and HPV infection in those living with solid organ transplant (SOT), end-stage renal disease (ESRD), hematopoietic stem cell transplant (HSCT), and autoimmune diseases (AID), specifically systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD) with addition of multiple sclerosis (MS) were researched. This update also summarizes data available on newer disease-modifying therapies (DMTs) including monoclonal antibodies (MABs). The authors then made recommendations for HPV vaccine administration, and screening using either general population guidelines or increased surveillance, the latter based on following current recommendations for women living with HIV. Additionally, the literature search included antibody response to HPV vaccines and recommendations for their administration for these same conditions. Results Based on the reviewed risks, evidence continued to support those persons living with SOT, ESRD, HSCT, and SLE, whether on immunosuppressant therapy or not, had an increased risk of HPV, squamous intraepithelial lesions, and CC whereas there was weak evidence that those persons with IBD, RA, and MS not on immunosuppressants were at risk. Data on persons using DMT/MAB were conflicting. Data showed that patients on certain immunosuppressants had lower antibody titers following HPV vaccination. There were no studies on HPV vaccine efficacy. Conclusions Following US Center for Disease Control and Prevention HIV Cervical cancer screening (CCS) guidelines is recommended for the following: SOT, ESRD, HSCT, and SLE whether on immunosuppressants or not, and IBD, RA, and MS on immunosuppressants. Shared decision-making about increased surveillance for IBD and RA not on immunosuppressants and persons on any DMT or MAB is reasonable based on conflicting data. Human papillomavirus vaccination should not change the recommendations for increased CC surveillance. A 3-dose series of the HPV vaccine is recommended for all age-eligible patients starting at 9 years of age, with catch-up to 26 years of age. Vaccination from age 27 up to age 45 years per Advisory Committee on Immunization Practices guidelines should be considered in shared decision-making. When possible, HPV vaccine series should be initiated and completed before SOT or initiation of DMT/MAB. For HSCT, the vaccine series should be readministered along with other childhood vaccines.

Evaluation of Host Gene Methylation as a Triage Test for HPV-Positive Women—A Cohort Study

Objectives This study was designed to evaluate the performance of a host gene methylation marker panel (ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671) in the triage of human papillomavirus (HPV)-positive women, its possible impact in a cervical cancer screening program, and the possible influence of the variation of the rate of HPV16/18 in its performance. Materials and Methods Cohort study in which consecutive women referred for colposcopy in an organized cervical cancer screening program had repeated HPV testing, colposcopy, and biopsies. The women that remained HPV positive at the time of colposcopy were tested with the panel of DNA methylation markers. The performance of the test was evaluated and compared to standard practice. Results The study test had a sensitivity and specificity for cervical intraepithelial neoplasia (CIN) 2+ of 60.8% (49.1–71.6%) and 88.4% (83.2–92.5%), respectively. For CIN3+, it was of 78.0% (64.0–88.5%) and 86.0% (80.8–90.2%), respectively. The rate and level of methylation positively correlated with the severity of disease. The use of methylation reduces the referral for colposcopy to 25.5%, while detecting 78.0% of the CIN3+ cases. Referral of all HPV16/18-positive cases and triage of the other high-risk HPV-positive cases with methylation, detects 90.0% of the cases of CIN3+, while reducing the number of referrals to 43.2%. The variation in the rate of HPV16/18 does not relevantly affect the performance of the methylation panel. Conclusions The studied methylation panel has a high sensitivity and specificity for CIN3+ and reduces the rate of referrals for colposcopy, without relevant variation according to the rate of HPV16/18.

Clinical Characteristics and Treatment Response With Checkpoint Inhibitors in Malignant Melanoma of the Vulva and Vagina

Objectives The aims of the study were to assess the clinical and histopathological characteristics of a comprehensive cohort of women with vulvovaginal melanoma (VVM) treated at our institution and to study the treatment response of checkpoint inhibitors in this patient cohort. Materials and Methods This is a retrospective study of women with invasive VVM treated at the Princess Margaret Cancer Centre in Toronto, Ontario, Canada, over a period of 15 years. Clinical and histopathological characteristics, treatment, as well as treatment-related outcome were analyzed in 32 women. Treatment response was evaluated retrospectively using the “response criteria for use in trials testing immunotherapeutics” (iRECIST). The objective response rate was defined as the proportion of patients with complete or partial response based on the best overall response. Results At a median follow-up of 37.8 months (5.8–110.4), 26 women (81.3%) had disease progression and 16 (50%) died. Thirteen patients with locally unresectable or metastatic melanoma were treated with immune checkpoint inhibitors. Ten additional cases were identified from previously published reports. The best objective response rate for immune checkpoint inhibitors was 30.4% (95% CI = 11.6%–49.2%) and the clinical benefit rate was 52.2% (95% CI = 31.8%–72.6%). The clinical benefit rate was significantly better for programmed cell death protein 1 inhibitors (or a combination) compared with ipilimumab alone (Fisher exact, p = .023). Grade 3/4 adverse events were observed in 3 (13.0%) of the 23 patients. Conclusions Women with VVM constitute a high-risk group with poor overall prognosis. Immune checkpoint inhibitors are effective in the treatment of metastatic melanoma in this patient cohort.

Risk of High-Grade Histopathology Diagnosed by Cervical Conization in Endocervical Curettage Cervical Intraepithelial Neoplasia 1: A Case-Control Study

Objective The aim of the study was to estimate risks of cervical intraepithelial neoplasia 2+ (CIN 2+) on loop electrosurgical excisional procedure (LEEP) specimens with the diagnosis of endocervical curettage (ECC) CIN 1 compared with biopsy CIN 1. Materials and Methods We performed a retrospective computer-based search for subjects enrolled in the Obstetrics and Gynecology Hospital of Fudan University. The case group comprised women with an ECC CIN 1 (ECC results of CIN 1 with colposcopy-directed biopsy results ≤CIN 1), and the control group comprised women with a biopsy CIN 1 (colposcopy-directed biopsy results of CIN 1 with negative ECC findings) diagnosis. Variables, including age, cytology, high-risk human papillomavirus, and ECC results, were included in univariate and multivariate logistic regression analyses. p < .05 was defined statistically significant. Results Overall, 1,195 women with ECC CIN 1 and/or biopsy CIN 1 diagnosis who underwent LEEP participated in the study. ECC CIN 1 comprised 400 women, with LEEP histopathology results revealing 104 (26.00%) CIN 2+. Biopsy CIN 1 comprised 795 women, with LEEP histopathology results showing 150 (18.87%) CIN 2+. Univariate logistic regression showed that cytology (p < .001) and ECC (p = .005) results differ significantly between less than CIN 2+ and CIN 2+. Multivariate logistic regression revealed that the cytology of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions (OR = 4.73, 95% CI = 2.78–8.05, p < .001) and high-grade squamous intraepithelial lesions or worse (HSIL+, OR = 4.88, 95% CI = 3.00–7.94, p < .001), and ECC CIN 1 (OR = 1.80, 95% CI = 1.33–2.44, p < .001) were risk factors for CIN 2 + . Conclusions Endocervical curettage CIN 1 has a greater risk of CIN 2+ diagnosis than biopsy CIN 1, but high-grade cytology has a higher risk than ECC CIN 1.

Risk Estimates Supporting the 2019 ASCCP Risk-Based Management Consensus Guidelines

Objective The 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines for the management of cervical cancer screening abnormalities recommend 1 of 6 clinical actions (treatment, optional treatment or colposcopy/biopsy, colposcopy/biopsy, 1-year surveillance, 3-year surveillance, 5-year return to regular screening) based on the risk of cervical intraepithelial neoplasia grade 3, adenocarcinoma in situ, or cancer (CIN 3+) for the many different combinations of current and recent past screening results. This article supports the main guidelines presentation 1 by presenting and explaining the risk estimates that supported the guidelines. Methods From 2003 to 2017 at Kaiser Permanente Northern California (KPNC), 1.5 million individuals aged 25 to 65 years were screened with human papillomavirus (HPV) and cytology cotesting scheduled every 3 years. We estimated immediate and 5-year risks of CIN 3+ for combinations of current test results paired with history of screening test and colposcopy/biopsy results. Results Risk tables are presented for different clinical scenarios. Examples of important results are highlighted; for example, the risk posed by most current abnormalities is greatly reduced if the prior screening round was HPV-negative. The immediate and 5-year risks of CIN 3+ used to decide clinical management are shown. Conclusions The new risk-based guidelines present recommendations for the management of abnormal screening test and histology results; the key risk estimates supporting guidelines are presented in this article. Comprehensive risk estimates are freely available online at https://CervixCa.nlm.nih.gov/RiskTables.

A Study of Partial Human Papillomavirus Genotyping in Support of the 2019 ASCCP Risk-Based Management Consensus Guidelines

Introduction The 2019 ASCCP Risk-Based Management Consensus Guidelines include recommendations for partial human papillomavirus (HPV) genotyping in management of abnormal cervical cancer screening results. The guidelines are based on matching estimates of cervical intraepithelial neoplasia (CIN) 3+ risk to consensus clinical action thresholds. In support of the guidelines, this analysis addresses the risks predicted by individual identification of HPV 16 and HPV 18. Methods Risk estimates were drawn from a subset of women in the Kaiser Permanente Northern California screening program, whose residual cervical specimens were HPV typed as part of the HPV Persistence and Progression study. We calculated risk of CIN 3+ to assess how identification of HPV 16, HPV 18, or 12 other “high-risk” HPV types would influence recommended clinical management of new abnormal screening results, taking into account current cytologic results and recent screening history. Immediate and/or 5-year risks of CIN 3+ were matched to clinical actions identified in the guidelines. Results Identification of HPV 16 at the first visit including HPV testing elevated immediate risk of diagnosing CIN 3+ sufficiently to mandate colposcopic referral even when cytology was Negative for Intraepithelial Lesions or Malignancy and to support a preference for treatment of cytologic high-grade squamous intraepithelial lesion. HPV 18 less clearly elevated CIN 3+ risk. Conclusions Identification of HPV 16 clearly mandated consideration in clinical management of new abnormal screening results. HPV 18 positivity must be considered as a special situation because of established disproportionate risk of invasive cancer. More detailed genotyping and use beyond initial management will be considered in guideline updates.

An Introduction to the 2019 ASCCP Risk-Based Management Consensus Guidelines

A Systematic Review of Tests for Postcolposcopy and Posttreatment Surveillance

Objective For the 2019 ASCCP Risk-Based Management Consensus Guidelines, we conducted a systematic review of diagnostic assays for postcolposcopy and posttreatment management. Materials and Methods A literature search was conducted to identify articles reporting on tests/assays for cervical cancer screening, triage, postcolposcopy surveillance, and posttreatment surveillance published between 2012 and 2019 in PubMed and Embase. Titles and abstracts were evaluated by co-authors for inclusion. Included articles underwent full-text review, data abstraction, and quality assessment. Pooled absolute pretest and posttest risk estimates were calculated for studies evaluating management of patients after treatment. Results A total of 2,862 articles were identified through the search. Of 50 articles on postcolposcopy, 5 were included for data abstraction. Of 66 articles on posttreatment, 23 were included for data abstraction and were summarized in the meta-analysis. The pooled posttreatment risk of cervical intraepithelial neoplasia (CIN) 2+ in all studies was 4.8% (95% CI = 3.4%–6.8%), ranging from 0.4%–19.5% (τ2 = 0.57) in individual studies. Among individuals testing negative for human papillomavirus (HPV) posttreatment, the risk of CIN 2+ was 0.69% (95% CI = 0.3%–1.5%); among individuals testing positive for HPV posttreatment, the risk of CIN 2+ was 18.3% (95% CI = 12.1%–26.6%) in all studies. All risk estimates were substantially higher for liquid-based cytology. The HPV–cytology co-testing provided slightly better reassurance compared with HPV alone at the cost of much higher positivity. Conclusions Despite a large number of published studies on postcolposcopy and posttreatment surveillance, only few met criteria for abstraction and were included in the meta-analysis. More high-quality studies are needed to evaluate assays and approaches that can improve management of patients with abnormal screening.

Incorporating Stakeholder Feedback in Guidelines Development for the Management of Abnormal Cervical Cancer Screening Tests

Objective The 2019 ASCCP Risk-Based Management Consensus Guidelines present a paradigm shift from results- to risk-based management. Patient and provider factors can affect guideline adoption. We sought feedback from stakeholders to inform guideline development. Materials and Methods To solicit provider feedback, we surveyed attendees at the 2019 ASCCP annual meeting regarding readiness to adopt proposed changes and used a web-based public comment period to gauge agreement/disagreement with preliminary guidelines. We elicited patient feedback via a brief survey on preferences around proposed recommendations for treatment without biopsy. Surveys and public comment included both closed-ended and free-text items. Quantitative results were analyzed using descriptive statistics; qualitative results were analyzed using content analysis. Results were incorporated into guideline development in real time. Results Surveys indicated that 98% of providers currently evaluate their patients' past results to determine management; 88% felt formally incorporating history into management would represent an improvement in care. Most providers supported expedited treatment without biopsy: 22% currently perform expedited treatment and 60% were willing to do so. Among patients, 41% preferred expedited treatment, 32% preferred biopsy before treatment, and the remainder were undecided. Responses from the public comment period included agreement/disagreement with preliminary guidelines, reasons for disagreement, and suggestions for improvement. Conclusions Stakeholder feedback was incorporated into the development of the 2019 ASCCP Risk-Based Management Consensus Guidelines. Proposed recommendations with less than two-thirds agreement in the public comment period were considered for revision. Findings underscore the importance of stakeholder feedback in developing guidelines that meet the needs of patients and providers.

Reporting and Assessing the Quality of Diagnostic Accuracy Studies for Cervical Cancer Screening and Management

Objective We adapted the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool for studies of cervical cancer screening and management and used the adapted tool to evaluate the quality of studies included in a systematic review supporting the 2019 Risk-Based Management Consensus Guidelines. Methods We evaluated the quality of all studies included in our systematic review for postcolposcopy (n = 5) and posttreatment (n = 23) surveillance using QUADAS-2 criteria. Subsequently, we adapted signaling questions to indications of cervical cancer screening and management. An iterative process was carried out to evaluate interrater agreement between 2 study authors (M.A.C. and N.W.). Discrepant ratings were discussed, and criteria were adapted accordingly. We also evaluated the influence of study quality on risk estimates and between study variation using stratified subgroup meta-analyses. Results Twelve signaling questions for bias assessment that were adapted to or newly developed for cervical cancer screening and management are described here. Interrater agreement on bias assessment increased from 70% to 83% during the adaptation process. Detailed assessment of bias and applicability showed that all studies on postcolposcopy management and 90% of studies on posttreatment management had high risk of bias in at least 1 domain. Most commonly, high risk of bias was observed for the patient selection domain, indicating the heterogeneity of study designs and clinical practice in reported studies. Conclusions The adapted QUADAS-2 will have broad application for researchers, evidence evaluators, and journals who are interested in designing, conducting, evaluating, and publishing studies for cervical cancer screening and management.

Clinical Utility of Human Papillomavirus Genotyping in Cervical Cancer Screening: A Systematic Review

Objective Thirteen human papillomavirus (HPV) genotypes are associated with the highest risk of cervical disease/cancer; however, the risk of disease progression and cancer is genotype dependent. The objective of this systematic review was to examine evidence for high-grade cervical intraepithelial neoplasia (≥CIN 3) risk discrimination using HPV genotyping. Materials and Methods A systematic review of English and non-English articles through MEDLINE, Cochrane, clinicaltrials.gov, and abstracts presented at relevant professional society conferences were searched from 2000 to 2019. Search terms included: cervical cancer screening, HPV genotyping, CIN, HPV persistence, humans, and colposcopy; prospective, controlled trials, observational studies, and retrospective studies of residual specimens; evidence included HPV genotyping (beyond genotypes 16/18/45) results. Data were obtained independently by authors using predefined fields. Risk of bias was evaluated with a modified Newcastle-Ottawa Scale. The Grading of Recommendations, Assessment, Development and Evaluation methodology facilitated overall quality of evidence evaluation for risk estimation. The study protocol was registered with the PROSPERO International Prospective Register of Systematic Reviews (CRD42018091093). The primary outcome was CIN 3 or worse risk both at baseline and at different follow-up periods. Results Of 236 identified sources, 60 full texts were retrieved and 16 articles/sources were included. Risk of bias was deemed low; the overall quality of evidence for CIN 3 or worse risk with negative for intraepithelial lesions or malignancies or low-grade squamous intraepithelial cytology was assessed as moderate; that with atypical squamous cells-undetermined significance and “all cytology” was assessed as high. Clinical and methodological heterogeneity precluded meta-analysis. Human papillomavirus genotyping discriminated risk of CIN 3 or worse to a clinically significant degree, regardless of cytology result. Conclusions The evidence supports a clinical utility for HPV genotyping in risk discrimination during cervical cancer screening.

Human papillomavirus Posttreatment Clearance Time in Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer

Objective The aim of the study was to determine an appropriate follow-up schedule for human papillomavirus (HPV) detection by evaluating the clearance time of HPV after treatment. Materials and Methods A retrospective study was conducted on 97 high-grade squamous intraepithelial lesion (HSIL) (cervical intraepithelial neoplasia 2–3) patients and 437 early invasive cervical cancer (CC) (stages Ia–IIa) patients who received radical surgery at the Affiliated Tumor Hospital of Xinjiang Medical University. Patient medical information, including personal information, pathological diagnosis, HPV infection status, and therapeutic methods, was obtained through the hospital's historical medical records management system. The clearance time of HPV was determined using Kaplan-Meier method analysis, and clearance time of HPV among different age groups, different grades, and different clinical stages were compared using the log-rank test. Results The median clearance time of all patients was 10.4 months. The median clearance time was longer in HSIL patients than in early invasive CC patients (p < .05). No statistical significance was found among different HSIL grades, CC stages, or patient age groups (P > 0.05). Conclusions Delaying first posttreatment follow-up to 9 months in patients at high risk of noncompliance could potentially reduce burden of cost and repeated clinical visits. This follow-up approach could be consistently applied to all women regardless of age, severity, and extent of disease.

Interobserver Variation in Vulvar Squamous Cell Cancer Depth of Invasion Using Two Measurement Methods

Objectives Depth of invasion (DOI) in vulvar squamous cell carcinoma (vSCC) predicts risk of nodal metastasis, with measurement >1 mm dictating the need for lymph node diagnostic procedures. In 2021, the International Federation of Gynecology and Obstetrics (FIGO) changed its advice on how pathologists measure DOI. Some organizations revised guidelines to this “New” method; others continued to endorse the FIGO 2009 “Old” method. This study compares interobserver variation of vSCC DOI using Old and New FIGO measurement strategies. Methods A single representative image was chosen from 50 consecutive vSCC excisions with reported DOI of 0.1–3 mm. Ten pathologists provided 2 electronic measurements for each, using Old and New methods. Statistical evaluation included analyses of variance, Student t-test, and the kappa statistic. Results The Old method yielded a larger mean DOI than the New [1.3 vs 0.9 mm; p < .001]. The Old method had a lower proportion of measurement disagreements spanning 1 mm (53%, κ = 0.65% vs 68%, κ = 0.6). Agreement by all pathologists of DOI being either ≤1 mm or >1 mm occurred in 29/50 cases (58%) using the Old and 26 (52%) using the New method. When at least 2 pathologists measured DOI >1 mm, interobserver variation was lower using the Old method in 30 (83%) of 36 cases [mean difference = −0.1 mm, t(280) = −2.78, p = .008]. Conclusions The FIGO 2021 DOI measurement method has higher interobserver variation than FIGO 2009, with this difference arising from tumors with DOI >1 mm. This finding, combined with inadequate international consensus and scant clinical outcome data, should trigger reconsideration of 2021 FIGO staging guidelines.

Dermatoscopy and Optical Coherence Tomography in Vulvar High-Grade Squamous Intraepithelial Lesions and Lichen Sclerosus: A Prospective Observational Trial

Objective This study aimed to examine potential discriminatory characteristics of dermatoscopy and dynamic optical coherence tomography (D-OCT) on vulvar high-grade squamous intraepithelial lesions (vHSIL) and lichen sclerosus (LS) compared with healthy vulvar skin. Methods A prospective observational clinical trial was performed in 10 healthy volunteers, 5 vHSIL and 10 LS patients. Noninvasive imaging measurements using dermatoscopy and D-OCT were obtained at several time points, including lesional and nonlesional vulvar skin. Morphologic features of vHSIL and LS were compared with healthy controls. Epidermal thickness and blood flow were determined using D-OCT. Patients reported tolerability of each study procedure, including reference vulvar biopsies. The main outcome measures were feasibility and tolerability of imaging modalities, dermatoscopy and OCT characteristics, OCT epidermal thickness and D-OCT dermal blood flow. Results The application of dermatoscopy and D-OCT is feasible and tolerable. In vHSIL, dermatoscopic warty structures were present. In LS, sclerotic areas and arborizing vessels were observed. Structural OCT in the vulvar area aligned with histology for hyperkeratosis and dermal-epidermal junction visualization. Currently, the OCT algorithm is unable to calculate the epidermal thickness of the uneven vulvar area. Dynamic optical coherence tomography showed statistically significant increased blood flow in LS patients (mean ± SD, 0.053 ± 0.029) to healthy controls (0.040 ± 0.012; p = .0024). Conclusions The application of dermatoscopy and D-OCT is feasible and tolerable in vHSIL and LS patients. Using dermatoscopy and D-OCT, the authors describe potential characteristics to aid differentiation of diseased from healthy vulvar skin, which could complement clinical assessments.

The Clinicopathologic Challenge of Nonneoplastic Vulvar Acanthosis

Objective The aim of the study was to evaluate clinicopathologic features of cases demonstrating an acanthotic tissue reaction not clearly consistent with psoriasis, lichen simplex chronicus, mycosis, or condyloma. Materials and Methods This is a retrospective pathologic case series of biopsies reported as “benign acanthotic lesion” and “acanthotic tissue reaction” that lacked a clear diagnosis on expert review. Cases with nuclear atypia were excluded. Clinical and histopathologic data were collected, immunohistochemistry for p16 and p53 were obtained, and molecular testing for 28 common anogenital human papillomavirus (HPV) genotypes was undertaken. Results There were 17 cases with a median age of 47 years. Unilaterality and medial location were clinical reasons for diagnostic difficulty. Histopathologic uncertainty often related to lack of papillary dermal fibrosis to support lichen simplex chronicus or psoriasiform lesions without parakeratosis, subcorneal pustules, and/or mycotic elements. Firm pathologic diagnoses were not possible, but 3 groups emerged: favoring chronic dermatitis, favoring psoriasis, and unusual morphologies. p16 results were negative or nonblock positive while p53 was normal or basal overexpressed. Human papillomavirus testing was negative in 12, low positive for HPV 16 in 1, unassessable in 3, and not requested in 1. Conclusions There is a group of acanthotic tissue reactions that cannot be classified with standard histopathologic assessment. Further clinicopathologic research into unilateral acanthotic lesions may provide insight into separation of psoriasis and mycosis when organisms are absent. Once nuclear atypia is excluded, immunohistochemistry for p16 and p53 and HPV molecular testing do not assist in diagnostic identification.

Diagnostic Criteria for Differentiated Vulvar Intraepithelial Neoplasia and Vulvar Aberrant Maturation

Objective The aim of the study was to describe the features required for diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar aberrant maturation (VAM). Materials and Methods The International Society of the Study of Vulvovaginal Diseases tasked the difficult pathologic diagnoses committee to develop consensus recommendations for clinicopathologic diagnosis of vulvar lichen planus, lichen sclerosus, and dVIN. The dVIN subgroup reviewed the literature and formulated diagnostic criteria that were reviewed by the committee and then approved by the International Society of the Study of Vulvovaginal Diseases membership. Results Differentiated vulvar intraepithelial neoplasia is the immediate precursor of human papillomavirus (HPV)–independent vulvar squamous cell carcinoma and shows a spectrum of clinical and microscopic appearances, some overlapping with HPV-related neoplasia. The histopathologic definition of dVIN is basal atypia combined with negative or nonblock-positive p16 and basal overexpressed, aberrant negative, or wild-type p53. The most common pattern of dVIN is keratinizing with acanthosis, aberrant rete ridge pattern, and premature maturation. The morphologic spectrum of keratinizing dVIN includes hypertrophic, atrophic, acantholytic, and subtle forms. A few dVIN cases are nonkeratinizing, with basaloid cells replacing more than 60% of epithelium. Vulvar aberrant maturation is an umbrella term for lesions with aberrant maturation that arise out of lichenoid dermatitis and lack the basal atypia required for dVIN. Conclusions Evaluation of women at risk for dVIN and VAM requires a collaborative approach by clinicians and pathologists experienced in vulvar disorders. Close surveillance of women with lichen sclerosus and use of these recommendations may assist in prevention of HPV-independent squamous cell carcinoma through detection and treatment of dVIN and VAM.

Clinicopathologic Diagnosis of Differentiated Vulvar Intraepithelial Neoplasia and Vulvar Aberrant Maturation

Objective The aim of the study was to describe the demographic, clinical, and histopathologic features of differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar aberrant maturation (VAM). Methods Specimens from 2010 to 2020 reported as dVIN or VAM were reviewed. Clinical data included age, rurality, symptoms, and evidence of lichen sclerosus (LS). Histopathologic data included epithelial thickness, keratinization, architectural and dyskeratotic features, stroma, p16, and p53. Differentiated vulvar intraepithelial neoplasia and VAM were distinguished by assessment of basal nuclear chromatin, enlargement, pleomorphism, and mitoses. Results One hundred twenty women with a median age of 71 years had 179 examples of dVIN and VAM. Squamous cell carcinoma was concurrent in 66% and associated with rurality. Ten percent were asymptomatic, and all but 3 had evidence of LS. Differentiated vulvar intraepithelial neoplasia showed a range of thickness, architecture, and dyskeratosis; its unifying !feature was basal atypia. Differentiated vulvar intraepithelial neoplasia displayed hyperchromasia in 83% and easily observed mitoses in 70%. Nonkeratinizing morphology, subcategorized into basaloid and intermediate, occurred in 24% of women with dVIN. Traditional dVIN represented 62% of keratinizing cases; the remainder were atrophic (13%), hypertrophic (13%), acantholytic (8%), or subtle (5%). Vulvar aberrant maturation had abnormal stratum corneum, acanthosis, premature maturation, and enlarged vesicular nuclei. Null p53 helped distinguish dVIN from VAM and dermatoses. Conclusions The morphology of dVIN encompasses nonkeratinizing and keratinizing types, the latter subdivided into traditional, acantholytic, atrophic, hypertrophic, and subtle. Diagnosis relies on basal atypia with supportive p16 and p53. Atypia exists on a biologic spectrum with mild abnormalities of VAM and reactive change. Identification of dVIN and VAM requires collaboration between clinicians and pathologists experienced in vulvar disorders.

Performance of Government-Financed Cervical Cancer Screening in Hunan, China, and Optimization of Triage Strategies

Objectives Cervical cancer is a preventable and manageable public health concern. This study aimed to evaluate the performance of a government-financed cervical cancer screening program and to discuss optimal primary screening approach and triage strategies for large-scale population screening. Methods This population-based study was conducted from 2015 to 2020 and included 6,373,279 eligible women. The performance of the cervical cancer screening program in Hunan Province was evaluated by comparing cancer incidence and mortality rates. The screening powers of primary human papillomavirus (HPV) testing and cytology were compared by calculating positive outcomes and cervical intraepithelial neoplasia 2 or worse (CIN2+) detection rates. Triage strategies for individuals positive for HPV-16/18 after primary HPV testing were discussed by comparing the CIN2+ detection rates and associated costs. Results The cervical cancer screening program has contributed to lower cancer mortality rates in Hunan Province. The HPV testing showed a higher CIN2+ detection rate than cytology as the primary screening approach (0.604% vs. 0.324%). For individuals positive for HPV-16/18, reflex cytology demonstrated a higher CIN2+ detection rate than direct colposcopy (51.11% vs 41.25%), although it was more expensive. For individuals with high-risk HPV types other than HPV-16/18, direct colposcopy exhibited a similar CIN2+ detection power as reflex cytology, but cost less. Conclusions The cervical cancer screening program should be expanded because the benefits outweigh the costs. Statistical data indicate that HPV testing is a cost-effective preliminary screening approach for large-scale population screening.

The Vaginal Microbiome: IV. The Role of Vaginal Microbiome in Reproduction and in Gynecologic Cancers

Objective This series of articles, titled The Vaginal Microbiome (VMB), written on behalf of the International Society for the Study of Vulvovaginal Disease, aims to summarize the recent findings and understanding of the vaginal bacterial microbiota, mainly regarding areas relevant to clinicians specializing in vulvovaginal disorders. Materials and Methods A search of PubMed database was performed, using the search terms “vaginal microbiome” with “reproduction,” “infertility,” “fertility,” “miscarriages,” “pregnancy” “cervical cancer,” “endometrial cancer,” and “ovarian cancer.” Full article texts were reviewed. Reference lists were screened for additional articles. Results The fourth article of this series focuses on 2 distinct areas: the role of VMB in various aspects of human reproduction and, in sharp contrast, the association between the VMB and gynecologic malignancies. Several of the negative pregnancy outcomes have been associated with an altered VMB. Dysbiosis is remarkably linked with poor pregnancy outcomes from preconception to delivery. The associations between the microbiome and gynecologic cancers are described. Conclusions The development of the microbiome research, enabled by molecular-based techniques, has dramatically increased the detection of microorganisms and the understanding of bacterial communities that are relevant to maternal-fetal medicine in health and disease, as well as in gynecological malignancies. Proving causation in cancer is difficult because of the complex interactive nature of potential causative factors. Certain elements of the microbiota have been shown to provoke inflammatory reactions, whereas others produce anti-inflammatory reactions; this balance might be impaired with a change in microbial variety.

Alinity m HR HPV Assay: United States Clinical Trial Design and High-Risk Human Papillomavirus Prevalence

Objective The Alinity m HR HPV assay is a qualitative molecular assay that simultaneously detects high-risk human papillomavirus (hr HPV) genotypes HPV16, 18, and 45 and reports the 11 other hr HPV genotypes in 2 aggregates as other HR HPV A (HPV31, 33, 52, 58) and other HR HPV B (HPV35, 39, 51, 56, 59, 66, 68). Here, the authors describe the prevalence of hr HPV genotypes in the Alinity m HR HPV assay US clinical trial population stratified by age, cytology, and cervical disease status. Methods This study included 11,532 women undergoing routine cervical cancer screening. Results Overall hr HPV positivity decreased with age. Other HR HPV B genotypes had the highest positivity followed by other HR HPV A, HPV16, HPV45, and HPV18. In the population with ≥atypical squamous cells of undetermined significance cytology, other HR HPV A and other HR HPV B genotypes had the highest positivity rates. HPV16 and other HR HPV A positivity rates were highest in specimens with ≥cervical intraepithelial neoplasia 3 by histology. Conclusions This analysis of primary screening participants in the Alinity m HR HPV assay US clinical trial demonstrates the benefits of including genotype-specific testing in cervical cancer screening programs.

ASCCP Clinical Consensus: Screening Recommendations for Clear Cell Adenocarcinomas in People Exposed to DES In Utero

Objectives The cohort of diethylstilbestrol (DES)-exposed people is aging, and a substantial fraction have already passed the age of 65, when unexposed average-risk people may exit cervical cancer screening provided they have had adequate prior screening. Current guidelines exclude individuals with a history of in utero exposure to DES. This clinical consensus includes a systematic review of relevant studies and provides updated guidance for surveillance of the aging DES-exposed cohort. Methods A literature search was performed to find all relevant DES and clear cell adenocarcinoma (CCA) papers that addressed key clinical questions. Study quality was assessed and recommendations were rated on strength (A–E) and quality of evidence (I–III) using the system described for previous American Society of Colposcopy and Cervical Pathology consensus guidelines. Results DES-exposed patients were 40 times more likely (standardized incidence ratio = 40.9; 95% CI, 13.1–126.2) to develop cervical and vaginal CCAs compared with unexposed individuals, with most cases diagnosed in individuals between the ages of 15 and 31. DES exposure in utero significantly increases the risk of CCA compared with nonexposed people, but the absolute risk of CCA is low. While CCA does seem to occur in older exposed patients, cases were rare and calculated incidence rates were extremely low, with the largest in any of the cohorts at 2.86 per million women-years. Conclusions The American Society of Colposcopy and Cervical Pathology recommends people with prenatal exposure to DES receive annual screening for CCA with cytology until the age of 65 and discontinue screening beyond the age of 65 provided they otherwise meet criteria for cessation of screening.

The Risk of Developing Cervical Cancer in the Elderly: Who Benefits From Screening After the Age of 60?

Objectives Population-based cervical cancer screening in the Netherlands ends at age 60. This retrospective cohort study aims to identify a subgroup of people over 60 years who are at increased cervical cancer risk, and may benefit from extended screening. Methods People with a cervix, aged 59–61 with an abnormal exit smear (index smear), conducted as part of the screening program between 2000 and 2004, were identified from the Dutch nationwide pathology databank. A 1:3 matching was obtained with people without an abnormal screening smear at the same age. Incidence rate ratios (IRR) were calculated for the risk of developing cervical cancer or cervical intraepithelial neoplasia (CIN) later in life. Up to 22 years of follow-up was obtained. Results A total of 10,368 people were identified. The IRR for CIN and cervical cancer was increased for people with an abnormal index smear. This risk was highest for people with a high-grade index smear, compared with a normal index smear; IRR of high-grade CIN of 104.05 (95% CI = 38.18–353.18) and IRR for cervical cancer of 18.58 (95% CI = 5.31–61.07). The majority (82%) of people with an abnormal index test showed normal cytology or histology preceding their CIN or cervical cancer. Conclusions People with a cervix with abnormal cytology in their exit screening smear 59–61 years showed a 19 times increased lifelong risk of cervical cancer and more than 100 times increased risk for CIN. Because this increased risk was not limited to a specific timeframe, prolonged screening or adjusted diagnostic follow-up for this specific group should be considered.

Cervical Cancer Prevention in Individuals With Criminal Legal System Involvement

Objectives Women with a history of criminal legal system involvement have cervical cancer rates that are 4–5 times higher than the general population—a disparity that has persisted for nearly 50 years. The authors’ objective is to describe the intersection of mass incarceration in the United States and risk factors for cervical cancer to offer equitable prevention and treatment strategies for the field. Methods A group was convened by American Society for Colposcopy and Cervical Pathology members and experts in the field to address a topic of importance relevant to cervical cancer elimination in underserved groups. This topic has received consistent attention from the American Society for Colposcopy and Cervical Pathology. After convening multiple times to discuss salient issues on the topic, the group proposed 12 specific recommendations related to vaccination, screening, treatment, practice, research, and policy to address the burden of cervical cancer among individuals with criminal legal system involvement. Results At least 10% of the incarcerated population is at risk for cervical cancer. Clinicians in all areas of practice will encounter patients with incarceration histories or current incarceration, regularly throughout their careers. Conclusions Clinicians who provide preventive care for people at risk of cervical cancer can play a critical role in eliminating disparities for this vulnerable population, by drawing on these expert recommendations.

Deep Learning Diagnostic Classification of Cervical Images to Augment Colposcopic Impression

Objective A deep learning classifier that improves the accuracy of colposcopic impression. Methods Colposcopy images taken 56 seconds after acetic acid application were processed by a cervix detection algorithm to identify the cervical region. We optimized models based on the SegFormer architecture to classify each cervix as high-grade or negative/low-grade. The data were split into histologically stratified, random training, validation, and test subsets (80%–10%–10%). We replicated a 10-fold experiment to align with a prior study utilizing expert reviewer analysis of the same images. To evaluate the model's robustness across different cameras, we retrained it after dividing the dataset by camera type. Subsequently, we retrained the model on a new, histologically stratified random data split and integrated the results with patients' age and referral data to train a Gradient Boosted Tree model for final classification. Model accuracy was assessed by the receiver operating characteristic area under the curve (AUC), Youden's index (YI), sensitivity, and specificity compared to the histology. Results Out of 5,485 colposcopy images, 4,946 with histology and a visible cervix were used. The model's average performance in the 10-fold experiment was AUC = 0.75, YI = 0.37 (sensitivity = 63%, specificity = 74%), outperforming the experts' average YI of 0.16. Transferability across camera types was effective, with AUC = 0.70, YI = 0.33. Integrating image-based predictions with referral data improved outcomes to AUC = 0.81 and YI = 0.46. The use of model predictions alongside the original colposcopic impression boosted overall performance. Conclusions Deep learning cervical image classification demonstrated robustness and outperformed experts. Further improved by including additional patient information, it shows potential for clinical utility complementing colposcopy.

Fanconi Anemia Complicated by Cervical Precancer, Vulvar, and Oral Squamous Cell Cancer

Recommendations for Use of p16/Ki67 Dual Stain for Management of Individuals Testing Positive for Human Papillomavirus

Objectives The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for dual stain (DS) testing with CINtec PLUS Cytology for use of DS to triage high-risk human papillomavirus (HPV)-positive results. Methods Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated according to DS results among individuals testing HPV-positive using data from the Kaiser Permanente Northern California cohort and the STudying Risk to Improve DisparitiES study in Mississippi. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Resource usage metrics were calculated to support decision-making. Risk estimates in relation to clinical action thresholds were reviewed and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group. Results For triage of positive HPV results from screening with primary HPV testing (with or without genotyping) or with cytology cotesting, colposcopy is recommended for individuals testing DS-positive. One-year follow-up with HPV-based testing is recommended for individuals testing DS-negative, except for HPV16- and HPV18-positive results, or high-grade cytology in cotesting, where immediate colposcopy referral is recommended. Risk estimates were similar between the Kaiser Permanente Northern California and STudying Risk to Improve DisparitiES populations. In general, resource usage metrics suggest that compared with cytology, DS requires fewer colposcopies and detects cervical intraepithelial neoplasia grade 3 or worse earlier. Conclusions Dual stain testing with CINtec PLUS Cytology is acceptable for triage of HPV-positive test results. Risk estimates are portable across different populations.

Human Papillomavirus Same Genotype Persistence and Risk: A Systematic Review

Objective The aim of the study was to examine whether high-grade cervical intraepithelial neoplasia (CIN) was more closely associated with human papillomavirus (HPV) same-genotype persistence (SGTP) versus clearance of prior infection with a subsequent infection by a new genotype (genotype switch [GS]), clearance of HPV infection, or acquisition of a new HPV infection after a negative infection status, during a follow-up testing subsequent to abnormal screening results. Materials and Methods MEDLINE, Cochrane Library, Health Technology Assessment, and clinicaltrials.gov were searched from January 2000 to July 2019 for prospective controlled trials and observational studies of women and retrospective studies using HPV assays with extended- or full-genotype reporting. The primary outcome was high-grade CIN after at least 2 rounds of testing. Overall quality of evidence for the risk estimate outcomes was assessed. Of the 830 identified abstracts, 66 full-text articles were reviewed, and 7 studies were included in the synthesis. The study protocol was registered with the PROSPERO International Prospective Register of Systematic Reviews (CRD42018091093). Results Continued HPV-positive women falls in 2 equally large groups: SGTP and GS. Sensitivity, positive predictive value, and positive likelihood ratio of SGTP were significantly higher than for GS. Human papillomavirus genotypes may be ranked into 3 tiers (immediate colposcopy, follow-up testing, return to routine screening), according to associated risk of persistence for high-grade CIN and to prevailing clinical action thresholds. Conclusions There is moderately high-quality evidence to support the clinical utility of SGTP to improve risk discrimination for high-grade CIN compared with qualitative HPV testing without genotype-specific information.

Agreement on Lesion Presence and Location at Colposcopy

Objectives/purpose The reproducibility and sensitivity of image-based colposcopy is low, but agreement on lesion presence and location remains to be explored. Here, we investigate the interobserver agreement on lesions on colposcopic images by evaluating and comparing marked lesions on digitized colposcopic images between colposcopists. Methods Five colposcopists reviewed images from 268 colposcopic examinations. Cases were selected based on histologic diagnosis, i.e., normal/cervical intraepithelial neoplasia (CIN)1 (n = 50), CIN2 (n = 50), CIN3 (n = 100), adenocarcinoma in situ (n = 53), and cancer (n = 15). We obtained digitized time-series images every 7–10 seconds from before acetic acid application to 2 minutes after application. Colposcopists were instructed to digitally annotate all areas with acetowhitening or suspect of lesions. To estimate the agreement on lesion presence and location, we assessed the proportion of images with annotations and the proportion of images with overlapping annotated area by at least 4 (4+) colposcopists, respectively. Results We included images from 241 examinations (1 image from each) with adequate annotations. The proportion with a least 1 lesion annotated by 4+ colposcopists increased by severity of histologic diagnosis. Among the CIN3 cases, 84% had at least 1 lesion annotated by 4+ colposcopists, whereas 54% of normal/CIN1 cases had a lesion annotated. Notably, the proportion was 70% for adenocarcinoma in situ and 71% for cancer. Regarding lesion location, there was no linear association with severity of histologic diagnosis. Conclusion Despite that 80% of the CIN2 and CIN3 cases were annotated by 4+ colposcopists, we did not find increasing agreement on lesion location with histology severity. This underlines the subjective nature of colposcopy.

Triage Value of Cervical Exfoliated Cell DNA Ploidy Analysis in Cervical High-Risk Human Papillomavirus–Positive Women

Objective This study aimed to investigate the triage value obtained in DNA ploidy analysis of cervical exfoliated cells in women with high-risk human papillomavirus (HR-HPV)-positive status in the primary screening of cervical cancer. Methods The authors selected 3,000 HR-HPV–positive women for cervical exfoliated cell sampling and conducted DNA ploidy analysis, liquid-based cytology (LBC), colposcopy, and cervical biopsy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of high-grade squamous intraepithelial lesion (HSIL)-positive detection between DNA ploidy analysis and LBC were compared according to histopathology diagnosis as the golden criteria, and the efficacy of predicting HSIL-positive immediate risk was evaluated. Results A total of 2,892 HR-HPV–positive women were enrolled in the investigation. For HSIL+ women, the DNA ploidy group showed a significantly higher sensitivity (CIN2+: 79.21% vs 65.35%, p = .022; CIN3+: 81.48% vs 70.37%, p = .013), lower specificity (CIN2+: 85.00% vs 96.59%, p < .001; CIN3+: 84.14% vs 93.41%, p < .001), and lower PPV (CIN2+: 16.23% vs 29.33%, p = .001; CIN3+: 8.92% vs 16.89%, p = .002) compared with the LBC group, whereas the NPV showed no significant difference. Compared with LBC alone in diagnosing HSIL, DNA ploidy combined with LBC showed higher specificity (CIN2+: 99.21% vs 96.59%, p = .003; CIN3+: 96.48% vs 93.41%, p < .001) and higher PPV (CIN2+: 41.35% vs 29.33%, p = .022; CIN3+: 24.81% vs 16.89%, p = .028), whereas no significant difference was observed in the sensitivity (CIN2+: 54.46% vs 65.35%, p = .063; CIN3+: 61.11% vs 70.37%, p = .221) and NPV ( p > .05). Among the HR-HPV–positive women positive for DNA ploidy, the imminent risk of CIN2+ and CIN3+ were 15.62% and 8.92%, respectively, above the threshold for the colposcopy positive rate. Among the positive cases both for DNA ploidy and the LBC result of negative for intraepithelial lesion or malignancy, the immediate risk of CIN3+ was 3.31%, below the threshold for colposcopy positive rate. Besides, for women with LBC result of ASC-US and above, the immediate risk of CIN3+ was greater than 4%. Conclusions The DNA ploidy analysis can be used as an effective triage method for HR-HPV–positive women during the primary screening of cervical cancer, although it can provide higher specificity when combined with LBC and reduce the referral rate for colposcopy.

ASCCP Committee Opinion: Adjuvant Human Papillomavirus Vaccine for Patients Undergoing Treatment for Cervical Intraepithelial Neoplasia

Objectives Individuals treated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) are at long-term risk of persistent or recurrent disease despite treatment. This committee opinion aims to summarize and provide evidence-based recommendations for adjuvant human papillomavirus (HPV) vaccination based on available, published literature. Methods A task force from the ASCCP Practice Committee reviewed current Centers for Disease Control and Prevention (CDC) guidelines and previously published literature about the role of adjuvant HPV vaccination in previously unvaccinated individuals undergoing treatment for CIN2+ and other HPV-related diseases. Results Current CDC guidelines recommend routine or catch-up HPV vaccination for individuals aged 9 to 26 years, and shared decision making regarding vaccination for individuals aged 27 to 45 years. Multiple published studies suggest a possible benefit for adjuvant HPV vaccination in previously unvaccinated individuals undergoing treatment for CIN2+. Conclusions The American Society for Colposcopy and Cervical Pathology recommends adherence to current CDC recommendations for vaccination of individuals aged 9 to 26 years and consideration of the possible benefit of adjuvant HPV vaccination during shared decision making for previously unvaccinated individuals aged 27 to 45 years who are undergoing treatment for CIN2+.

Risk Factor and Treatment of Vaginal Intraepithelial Neoplasia After Hysterectomy for Cervical Intraepithelial Neoplasia

Objectives The aim of the study were to identify the risk factors for recurrent vaginal intraepithelial neoplasia (VaIN)1+ and to evaluate the efficacy of laser vaporization in patients who underwent hysterectomy for the treatment of cervical intraepithelial neoplasia (CIN). Methods Medical records of 374 women who underwent hysterectomy for the treatment of CIN were retrospectively reviewed. Recurrence was defined as VaIN1+ diagnosis by colposcopy-directed biopsy. Results Among 374 patients, 36 (9.6%) had VaIN1+ during a median follow-up of 32 (0–193) months: 13 (3.5%) had VaIN1, 6 (1.6%) VaIN2, 15 (4.0%) VaIN3, and 2 (0.5%) invasive cancer. Multivariate analysis showed that age of greater than 50 years was the only independent risk factor for VaIN1+ recurrence (odds ratio, 3.359; 95% CI, 1.60–7.07; p = .001). Among the 34 patients with VaIN, 21 (61.8%) were treated with laser vaporization and 11 (32.3%) were observed without treatment. Time to second recurrence was longer in the VaIN treated by laser vaporization group than that in the observation group (mean time to subsequent recurrence, 128.7 [95% CI, 101.4–156.0] vs. 41.8 [15.7–67.9] months; p = .003). Moreover, laser vaporization (hazard ratio, 0.125; 95% CI, 0.03–0.59; p = .009) was the only independent good prognostic factor for the second VaIN1+ recurrence. Conclusions Patients older than 50 years who underwent hysterectomy for the treatment of CIN might be highly at risk of VaIN1+. Laser vaporization is the only independent prognostic factor that might prevent the second VaIN1+ recurrence.

Anogenital High-Grade Squamous Intraepithelial Lesion Comorbid With Vulvar Lichen Sclerosus and Lichen Planus

Objective The aim of the study was to describe the clinicopathologic features of vulvovaginal or anal high-grade squamous intraepithelial lesion (HSIL) comorbid with lichen sclerosus and/or lichen planus (LS/LP). Methods The local pathology database identified 37 consecutive cases from 2007 to 2019 of vulvar, vaginal, or anal HSIL among women who had a histopathologic diagnosis of vulvar LS/LP. Cases had p16 and p53 immunoperoxidase stains. Clinical data included age, relative location of HSIL and LS/LP, immune-modifying conditions, tobacco use, treatment type, and follow-up. Histopathologic data included HSIL morphology categorized as warty-basaloid or keratinizing, p16 and p53 patterns within HSIL, and features of LS/LP. Results The mean age was 69 years with a median follow-up up 42 months. Lichen sclerosus, alone or in combination with LP, was the comorbid dermatosis in 89%. Lichen sclerosus/lichen planus was overlapping or adjacent to HSIL in two-thirds of cases and located separately in the remainder. Rates of tobacco use and immunologic dysfunction were each 40%. In cases of co-located LS and HSIL, sclerosis was absent under the neoplasia in 57%. Twenty-four percent of HSIL cases showed keratinizing morphology; block-positive p16 and suprabasilar-dominant p53 helped distinguish HSIL from human papillomavirus–independent neoplasia. Conclusions Histopathologic identification of comorbid HSIL and LS/LP may be challenging because of keratinizing morphology and loss of diagnostic features of LS. Clinicopathologic correlation and use of p16 and p53 are essential to achieve an accurate diagnosis and enact disease-specific management plans.

Precise Measurement of the Thickness of Vaginal Intraepithelial Neoplasia

Objectives Although carbon dioxide laser vaporization is frequently used for treating vaginal intraepithelial neoplasia (VaIN), the optimal depth of epithelial destruction with laser vaporization requires elucidation. We aimed to evaluate VaIN depth and better illustrate epithelial destruction during laser vaporization. Materials and Methods We included 246 women diagnosed with VaIN (low-grade VaIN [VaIN 1], 123 women; high-grade VaIN [VaIN 2/3], 123 women) using colposcopy-directed biopsy at our hospital from January 1, 2019, to April 30, 2020. The thickness of the noninvolved epithelium, if available, was determined. All available data, including cytology and histological information, were recorded. The t test and Pearson χ2 test were used for statistical analysis. Statistical significance was set at p < .05. Results The involved epithelial thicknesses in VaIN 2/3 and VaIN 1 were 0.41 ± 0.21 and 0.40 ± 0.19 mm, respectively, which were both greater than their noninvolved epithelial thickness values (0.17 ± 0.10 and 0.17 ± 0.08 mm, p < .01 and p < .01, respectively). In subgroup comparisons between the VaIN 2/3 and VaIN 1 groups, the involved epithelial thickness did not differ between premenopausal patients, postmenopausal women receiving estrogen, and postmenopausal women who did not receive estrogen (p > .05). In the VaIN 2/3 group, the lesion thickness in premenopausal was greater than that in postmenopausal women receiving estrogen (p = .016) and those who were not receiving estrogen (p = .017). Conclusions The thickness of VaIN is generally less than 1 mm for women of all ages, except in rare cases of visible lesions with papillary hyperplasia.

Near-Histologic Resolution Images of Cervical Dysplasia Obtained With Gabor Domain Optical Coherence Microscopy

Objective Histopathology is the criterion standard for evaluating cervical squamous intraepithelial neoplasia (dysplasia). In this pilot feasibility study, we examined whether a novel 3-dimensional imaging device using Gabor-domain optical coherence microscopy (GDOCM) could distinguish features of cervical dysplasia comparable with histopathology. Methods A prospective observational pilot study enrolled a small sample of women undergoing loop electrosurgical excision procedure for cervical squamous intraepithelial neoplasia. Fresh ex vivo specimens were imaged with the GDOCM device. Digital images were reviewed by a pathologist who was blinded to the histopathology results. Histopathologic features were then compared with the digital observations. Results Standard histologic features of cervical squamous epithelium and of squamous intraepithelial neoplasia could be observed in GDOCM images. Cervical epithelium, stroma, basement membrane, and squamous papilla could all be identified. Human papillomavirus effects, such as vacuolization and cellular density, were also observed. Conclusions A GDOCM imaging system has the potential to obtain histologic resolution images of the cervix in the evaluation of squamous intraepithelial neoplasia. This pilot study allowed for optimizing the imaging system and paved the way for a future diagnostic accuracy study. The development of this technology could streamline the evaluation of patients at risk for cervical neoplasia.

Dynamic Spectral Imaging Colposcopy Versus Regular Colposcopy in Women Referred With High-Grade Cytology: A Nonrandomized Prospective Study

Objective The aim of the study was to evaluate the sensitivity of dynamic spectral imaging (DSI) colposcopy compared with regular colposcopy for women referred with high-grade cervical cytology. Methods In a prospective, nonrandomized, multicenter study, we included women referred for colposcopy at hospital gynecology clinics with high-grade cytology. Women were examined using either a regular or DSI colposcope. In both groups, colposcopists located 1 area viewed as most suspicious. In the DSI group, this was done before viewing the DSI map. Subsequently, an area was chosen based on the worst color of the DSI map, and further additional biopsies were taken. All women had 4 cervical biopsies taken, all analyzed separately. The main outcome was sensitivity to find cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Results A total of 261 women were examined using DSI colposcopy, and 156 women were examined using regular colposcopy. The sensitivity for finding CIN2+ when using the DSI technology as an adjunctive technology was found to be 82.2% (95% CI = 75.9–87.4), based on an average of 1.4 biopsies. This was corresponding in sensitivity to 2 biopsies taken using regular colposcopy (80.3%; 95% CI = 72.3–86.8). There was no difference in sensitivity for CIN+ between the groups when 3 or more biopsies were taken. Conclusions We found that the DSI colposcope may help direct biopsy placement; however, the improvement is based on small differences in needed biopsies and the clinical significance of this may be small. Multiple biopsies were still superior.

Cervical Screening Practices and Outcomes for Young Women in Response to Changed Guidelines in Calgary, Canada, 2007–2016

Objective The aim of the study was to describe temporal trends in screening and outcomes for women, after changes in guidelines in Alberta, Canada, that raised starting age to 21 years, then to 25 years of age, and reduced frequency to 3 yearly. Materials and Methods Calgary Laboratory Information System data were used to examine screening rates, follow-up procedures, and cancer among women 10–29 years from 2007 to 2016 in the whole population of Calgary. Interrupted time-series analyses were used to assess changes in screening and subsequent diagnostic procedures over the 10-year period. Results Annual screening rates dropped by approximately 10% at all ages older than 15 years after the 2009 Alberta cervical cancer screening guidelines, followed by a steady decrease. Further change continued subsequent to minimal apparent effect of the 2013 Canadian Task Force on Preventive Health Care guidelines. The rates of abnormal test results decreased in concert with decreased screening. No increases in cervical intraepithelial neoplasia 1, cervical intraepithelial neoplasia 2/3, or invasive cervical cancer rates were observed after reduced testing. Conclusions The largest decrease in screening and follow-up procedures occurred in the period immediately after implementation of 2009 Alberta screening guidelines. The number of consequent procedures also decreased in proportion to decreased screening, but there was no increase in cancer rates. Starting screening at the age of 25 years and reducing intervals seem to be safe.

Identification of Specific Tumor Markers in Vulvar Carcinoma Through Extensive Human Papillomavirus DNA Characterization Using Next Generation Sequencing Method

Objectives A subset of vulvar carcinomas (VC) are associated with human papillomavirus (HPV) DNA. This trait can be used to identify tumor markers for patient's follow-up. A large diversity of HPV prevalence in VC has been reported, but no data are available concerning the insertional HPV status in this tumor type. Therefore, we have used an innovative next generation sequencing (NGS)-based CaptHPV method able to provide an extensive characterization of HPV DNA in tumors. Material and Methods Tumor tissue specimens from 55 patients with VC were analyzed using p16 immunohistochemistry, in situ hybridization, polymerase chain reaction, and CaptHPV-NGS assays. Results Our analyses showed that 8 (14.5%) of 55 cases were associated with HPV 16 DNA. No other HPV genotypes were identified. The HPV genome was in a free episomal state only in one case and both episomal and integrated into the tumor cell genome in 7. There was a single insertion in 5 cases and multiple sites, scattered at different chromosomal loci in two. ISH data suggest that some of these might reflect tumor heterogeneity. Viral integration targeted cellular genes among which were TP63, CCDC148, LOC100133091, PKP1, and POLA2. Viral integration at the PKP1 locus was associated with partial gene deletion, and no PKP1 protein was detected in tumor tissue. Conclusions Using the NGS-based innovative capture-HPV approach, we established a cartography of HPV 16 DNA in 8 VC cases and identified novel genes targeted by integration that may be used as specific tumor markers. In addition, we established a rationale strategy for optimal characterization of HPV status in VC.

Risk of Vulvar HSIL and Penile Neoplasias in Anogenital Lichen Planus: A Case-Control Study

Objective Lichen planus (LP) is a chronic inflammatory skin disease that may affect the skin, scalp, nails, and mucosa. The aim of this study was to investigate the risk of genital premalignant and malignant conditions in patients with anogenital LP (agLP). Methods The authors identified 60 male and 56 female patients with agLP by searching the biobank archives for a genital or perianal skin biopsy showing LP between 2004 and 2020. They also included 10 randomly selected age- and sex-matched controls for each patient. The risks of genital cancers and their precursors were evaluated. Results The incidence of agLP was 1.54 per 100,000 men and 1.36 per 100,000 women. There was no statistical difference between male and female incidence (p = .5721). The odds ratio (OR) for high-grade squamous intraepithelial lesion (HSIL) of the vulva was 31.2 (95% CI = 2.46–1645.00; p = .01). The OR for penile neoplasias could not be calculated because control patients had no neoplasias, but the difference was suggestive of statistical significance (95% CI = 1.90–infinite; p = .008). The mean age at the time of diagnosis of agLP was 59.9 years (median 62 years) in female patients and 40.8 years (median 33 years) in male patients. The difference in the mean ages of female and male patients was statistically significant (95% CI = 11.92–26.13; p < .001). Conclusions Patients with agLP may have an increased risk for vulvar HSIL and penile neoplasia.

Performance of Xpert HPV on Self-collected Vaginal Samples for Cervical Cancer Screening Among Women in South Africa

Objectives Self-sampling may increase access to cervical cancer screening in low-resource settings. Using Xpert HPV, we compared test performance of self- and clinician-collected samples in HIV-positive and HIV-negative women in South Africa. Materials and Methods Three hundred thirty HIV-positive and 375 HIV-negative women in the screening group and 202 HIV-negative and 200 HIV-positive women in the referral group, aged 30–65 years, participated in the study. All women self-collected a vaginal sample, and then, a cervical sample was collected by a clinician (both tested using Xpert HPV), followed by colposcopic examination and collection of histologic specimens. Results There was good agreement between self- and clinician-collected samples for detection of any high-risk human papillomavirus (HPV, κ = 0.72 [95% CI = 0.669–0.771]). Prevalence of HPV and sensitivity of the test to detect cervical intraepithelial neoplasia 2+ was similar in self- and clinician-collected samples. Specificity was lower in self-collected than in clinician-collected samples in both HIV-negative (self: 77.5% [95% CI = 72.8–81.8] vs clinician: 86.9% [95% CI = 82.9–90.2]) and HIV-positive (self: 44.0% [95% CI = 38.0–50.1] vs clinician: 59.7% [95% CI = 53.6–65.6]) women. Restricting the definition of screen-positive to 3 of 5 channels on HPV Xpert improved specificity in both HIV-negative (self: 83.2% [95% CI = 78.8–87.0] vs clinician: 89.7% [95% CI = 86.1–92.7]) and HIV-positive (self: 54.2% [95% CI = 48.1–60.2] vs clinician: 67.4% [95% CI = 61.5–72.9]) women. Conclusions The self-collected sample had good agreement with the clinician-collected sample for the detection of HPV, and restricting the HPV types may improve the specificity in HIV-positive women.

Factors Associated With Timely Receipt of Colposcopy After Abnormal Cervical Cancer Screening

Objective The aim of the study was to examine factors associated with timely colposcopy following abnormal cervical cancer screening among patients receiving care at an urban safety-net obstetrics and gynecology clinic. Methods In this cohort study, the authors reviewed the care cycle of index abnormal cervical cancer screening requiring colposcopy follow-up from 3 separate years: 2016, 2018, and 2021. Primary outcomes included colposcopy attendance and timely colposcopy evaluation based on established guidelines. Multivariable log binomial regression models were used to evaluate patient characteristics and outcomes. Results Across the 3 years, the authors identified 820 abnormal cervical cancer screening results from 752 patients for which a colposcopy was indicated. Of these patients, 42.2% identified as non-Hispanic Black, 79.7% were English-speaking, and 80.0% were publicly insured. Pap tests requiring colposcopy resulted in completion 85.2% of the time, with 59.8% completed within guideline-concordant intervals. Human papillomavirus–vaccinated patients were less likely to attend colposcopy (relative risk [RR] = 0.84, 95% confidence interval [CI] = 0.76–0.93). Current smokers had lower colposcopy attendance compared to never-smokers (RR = 0.89, 95% CI = 0.81–0.98). Timely colposcopy took place 59.6% of the time in 2016, 56.9% of the time in 2018, and 63.3% of the time in 2021. Patients aged 40–49 and 50–64 were more likely to complete colposcopy within guideline recommended intervals than those younger than age 30 (RR = 1.23, 95% CI = 1.03–1.47; RR = 1.38, 95% CI = 1.15–1.66). Conclusions Despite modest overall improvement in the rate of guideline-concordant colposcopy attendance, significant gaps in timely follow-up persist. Targeted interventions are needed to improve follow-up care, particularly for younger patients and smokers.

Recurrence After Biopsy-Confirmed Cervical High-Grade Intraepithelial Lesion Followed by Negative Conization: A Systematic Review and Meta-analysis

Abstract The aim of the study is to assess the recurrence rate (as cervical intraepithelial neoplasia 2+ [CIN2+]) in patients who had a confirmed high-grade squamous intraepithelial lesion (CIN2–3) in a cervical biopsy specimen followed by a negative conization specimen. Materials and Methods A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Ovid/MEDLINE, Ovid/Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception until January 2023. The study protocol was registered in PROSPERO (ID number CRD42023393951). The search identified 3,089 articles; 1,530 were removed as duplicates, and 1,559 titles and abstracts were assessed for inclusion. The full text of 26 studies was assessed for eligibility, and finally, 12 studies with 1,036 patients were included. All included studies were retrospective cohort studies. A proportion meta-analysis was performed. Results For patients with negative conization specimens, the recurrence rate as CIN2+ during follow-up was 6% (95% CI, 1.8%–12.1%; I 2 = 49.2; p < .0001, 215 patients and 4 studies) in the proportion meta-analysis, ranging from 0.3% to 13.0% for the individual studies. For patients with ≤CIN1 conization specimens, the recurrence rate as CIN2+ during follow-up was 3.6% (95% CI, 1.2%–7%; I 2 = 75.1; p < .0001, 991 patients and 10 studies) in the proportion meta-analysis and ranged from 0.6% to 13.0% for the individual studies. Conclusions The recurrence rate as CIN2+ for patients with a confirmed high-grade intraepithelial lesion on a cervical biopsy followed by a negative conization specimen is 6%. In patients with negative and CIN1 conization specimens, the recurrence rate is 3.6%.

Defining the Longitudinal Risk of CIN 3+ for <CIN 2 Colposcopy for Patients Referred With High-Grade Cytology

Objective To determine the baseline and cumulative risk of cervical intraepithelial neoplasia (CIN)3 and invasive cervical cancer in participants referred to colposcopy with high-grade cytology and <CIN2 histology, stratified by biopsy result. Methods The authors linked administrative databases including cytology, pathology, cancer registries, and physician billing history to identify participants referred to colposcopy between January 2012 and December 2013 with high-grade cytology (atypical squamous cells [ASC]-H, high-grade squamous intraepithelial lesion [HSIL], invasive squamous cell carcinoma, adenocarcinoma, atypical glandular cells [AGC], adenocarcinoma in situ) and had <CIN2 (with and without biopsy confirmation) at colposcopy. Three- and 5-year risks of CIN3 and invasive cervical cancer were generated using Kaplan-Meier survival analysis. Results Among 4,168 women referred to colposcopy for ASC-H, HSIL, squamous cell carcinoma, or adenocarcinoma, the 3- and 5-year CIN3 incidence rates were 17.7%/20.0% no biopsy, 13.0%/15.1% negative biopsy, and 18.9%/20.0% low-grade squamous intraepithelial lesion (LSIL) biopsies. The 3- and 5-year incidences of invasive cancer were: 1.25%/1.68% no biopsy, 0.78%/1.04% negative biopsy, and 0%/0% LSIL biopsy. When the initial cytology was AGC/adenocarcinoma in situ (n = 944), the 3- and 5-year rates of CIN3 were 7.42%/8.39% no biopsy, 7.41%/9.26% negative biopsy, and 7.69%/7.69% LSIL biopsy. The invasive cancer rates were 1.12%/1.54% no biopsy, 0.46%/0.46% negative biopsy, and 0.0%/0.0% LSIL biopsy. By screening cytology, participants referred for HSIL had the highest 3- and 5-year rates of CIN3 (18.9% and 21%) compared with AGC (7.22%/8.28%) and ASC-H (15.5%/18%). The 3- and 5-year invasive cancer rates were 1.38%/1.75% HSIL, 0.85%/1.17% AGC, and 0.91%/1.36% ASC-H. Conclusions In participants referred for high-grade cytology where colposcopy shows <CIN2, the subsequent risk of invasive cancer at 5 years is sufficiently elevated to warrant close surveillance in colposcopy.

Clinical Characteristics and Detection Sensitivity of Cervical Cancer Screening in Vaginal Intraepithelial Neoplasia

Objective This study aimed to investigate the characteristics and screening history of vaginal intraepithelial neoplasia (VaIN) or vaginal cancer and compare the sensitivity of cytology and human papillomavirus (HPV) tests on the cervix against vaginal and cervical high-grade squamous intraepithelial lesion or cancer. Methods This study included patients who underwent colposcopy-directed biopsy and were diagnosed with VaIN or vaginal cancer from February 2013 to November 2022. Clinical information was obtained from the medical records of the department. Statistical analysis was performed on SPSS 26.0 (IBM Corp, Armonk, NY) using t test, chi-square, and Fisher exact tests. Results A total of 1,166 patients were included in this study. The median age of VaIN2+ patients was 50.5 years, whereas VaIN1 reported a median age of 42.1 years old, p < .001. This study reported that VaIN was significantly and positively correlated with cervical lesions (r = 0.244). The high-risk HPV (hr-HPV) detection rate was 88.2% (858/973) in VaIN and 95.2% in VaIN2+. Human papillomavirus 16 was the most prevalent HPV type in VaIN2+, which accounted for 54.9%, followed by HPV58 (19.5%), HPV52 (15.2%), HPV51 (12.2%), and HPV18 (11.0%). The sensitivity of hr-HPV and cytology tests on the cervix for detecting VaIN2+ was 94.7% and 83.4%, respectively. Both tests were not significantly different from detecting cervical intraepithelial neoplasia 2+. Conclusions Human papillomavirus 16 is the dominant HPV type in vaginal precancer lesions. Cervical cancer screening has similar sensitivity for VaIN2+ as for cervical intraepithelial neoplasia 2+, with hr-HPV testing showing higher sensitivity than cytology.

Do High Rates of Atypical Glandular Cells Correlate With Higher Incidence of Disease in a Large Safety Net Hospital

Objective The aim of the study was to describe the incidence and correlates of atypical glandular cell (AGC) Pap tests in a low socioeconomic status, underserved population. Materials and Methods Medical records of patients with AGC Pap tests at a single institution were reviewed from January 2013 to August 2019. Baseline characteristics were extracted including age, body mass index, birth control, abnormal uterine bleeding, and human papillomavirus (HPV). All colposcopy and endometrial biopsies were classified into negative/low-risk (polyps, tubular metaplasia, microglandular hyperplasia, cervical intraepithelial neoplasia 1) and high-risk (HR) lesions (cervical intraepithelial neoplasia 2/3, adenocarcinoma in situ, endometrial hyperplasia, cervical cancer, endometrial cancer). Logistic regression identified significant associations. Sixty-eight randomly selected AGC cytology slides from the cohort and 32 non-AGC slides outside the cohort were blindly reviewed by 6 pathologists. Fleiss κ interrater agreement was assessed. Results Seven hundred forty patients with AGC Pap tests were identified (0.8% of all Pap tests performed during this time). After excluding for incomplete data, 478 patients were included. Sixty-three patients had HR lesions (13.3%). Patients with HR lesions had increased odds of abnormal uterine bleeding (odds ratio = 4.32, p < .001) and HPV positivity (odds ratio = 10.89, p < .001) when compared with patients with low-risk lesions. The κ agreement was 0.21 for all cases and 0.18 for AGC alone. Conclusions This population falls within the national averages for AGC Pap tests. There was an increased risk of HR lesions in patients with abnormal uterine bleeding and HPV positivity. The rate of HR lesions among AGC Pap tests was at the lower end of values in the literature. After blinded pathologist review, interobserver κ agreement was low for AGC Pap tests.

Recurrence in Cervical High-Grade Squamous Intraepithelial Lesion: The Role of the Excised Endocervical Canal Length—Analysis of 2,427 Patients

Objective This study aimed to evaluate the influence of the excised canal length on relapse rates of cervical high-grade squamous intraepithelial lesion (HSIL) treated by loop electrosurgical excision procedure and to find a cut-off point, above which lower recurrence rates could be observed, with low probability of compromising future obstetric outcome, and the relationship with other individual factors related to HSIL recurrence. Method This was a retrospective cohort study of 2,427 women diagnosed with cervical intraepithelial neoplasia CIN2+ who underwent cervical conization using the high-frequency loop electrosurgical excision procedure surgery technique, to analyze the role of endocervical canal length associated with individual factors in the recurrent disease after CIN2+ treatment and determine a cut-off point for the excised canal length needed to decrease the risk of disease relapse. Results In 2,427 cases, the relapse rate of HSIL treated was 12%. Compromised margins of conization, HIV+, and endocervical canal length were related directly to relapses (p < .001). The cut-off point, by receiver operating characteristic curve, to calculate the endocervical canal length related to relapses was 1.25 cm of canal excised. Canal length of less than 1.25 cm increased the recurrence rate 2.5 times. Compromised margins and HIV+ increased recurrence rates by more than 5 times. Conclusion Cervical HSIL recurrence was directly related to the endocervical canal length: excised canal length of 1.25 cm or more decreases recurrence rate; HIV and compromised margins increase the chance of recurrence by more than 5 times.

Nonsquamous Lesions of the Vulvar Skin and Subcutaneous Tissue: A Review (Part 1)

Objectives This article aimed to review “nonsquamous lesions of the vulvar skin and subcutaneous tissue” clinically and pathologically, based on the fifth edition of the World Health Organization tumor classification. Materials and Methods A database search of PubMed and Google Scholar was performed between 1970 and 2021, using the search terms “vulva,” “lower genital tract,” and “nonsquamous lesions.” The search was limited to “humans,” “gynecopathology,” and “dermatopathology.” Full article texts were reviewed. Reference lists were screened for additional articles. We excluded articles written in the non-English language and abstracts. Results A list of 600 articles was identified. Another screening identified 68 articles for clinicopathological features of nonsquamous lesions of the vulvar skin and subcutaneous tissue. In the first part of this review, we cover 5 major groups of nonsquamous lesions of the vulvar skin and subcutaneous tissue including (1) glandular tumors and cysts, (2) adenocarcinomas of other types, (3) germ cell tumors of the vulva, (4) neuroendocrine neoplasia, and (5) hematolymphoid hyperplasia and neoplasia. The rest of the major topics including mesenchymal tumors of the lower genital tract, melanocytic lesions, and metastasis will be discussed in the second part of this review. Conclusions Clinicopathological features of nonsquamous lesions of the vulvar skin and subcutaneous tissue as categorized by the updated World Health Organization classification are presented.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) Consensus Statement on the Management of Vaginal Intraepithelial Neoplasia

Abstract The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vaginal intraepithelial neoplasia (VaIN). The management of VaIN varies according to the grade of the lesion: VaIN 1 (low grade vaginal squamous intraepithelial lesions (SIL)) can be subjected to follow-up, while VaIN 2–3 (high-grade vaginal SIL) should be treated. Treatment needs individualization according to the patient’s characteristics, disease extension and previous therapeutic procedures. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Total vaginectomy is used only in highly selected cases of extensive and persistent disease. Carbon dioxide (CO2) laser may be used as both an ablation method and an excisional one. Reported cure rates after laser excision and laser ablation are similar. Topical agents are useful for persistent, multifocal lesions or for patients who cannot undergo surgical treatment. Imiquimod was associated with the lowest recurrence rate, highest human papillomavirus (HPV) clearance, and can be considered the best topical approach. Trichloroacetic acid and 5-fluorouracil are historical options and should be discouraged. For VaIN after hysterectomy for cervical intraepithelial neoplasia (CIN) 3, laser vaporization and topical agents are not the best options, since they cannot reach epithelium buried in the vaginal scar. In these cases surgical options are preferable. Brachytherapy has a high overall success rate but due to late side effects should be reserved for poor surgical candidates, having multifocal disease, and with failed prior treatments. VaIN tends to recur and ensuring patient adherence to close follow-up visits is of the utmost importance. The first evaluation should be performed at 6 months with cytology and an HPV test during 2 years and annually thereafter. The implementation of vaccination against HPV infection is expected to contribute to the prevention of VaIN and thus cancer of the vagina. The effects of treatment can have an impact on quality of life and result in psychological and psychosexual issues which should be addressed. Patients with VaIN need clear and up-to-date information on a range of treatment options including risks and benefits, as well as the need for follow-up and the risk of recurrence.

The Distribution of Cervical Transformation Zone and Its Impact on Colposcopic Diagnosis: A Multicenter Study in China

Objective The value of the transformation zone (TZ) is often overlooked in clinical settings. This study aims to assess TZ distribution, associated factors, and its impact on colposcopic diagnosis. Methods χ2 tests were used to analyze demographics, clinical history, and tissue samples to examine the differences in TZ distribution. Factors affecting the TZ were explored using logistic regression, and diagnostic indicators were calculated. Results A total of 5,302 individual datasets were finally included. TZ1, TZ2, and TZ3 accounted for 31.6%, 38.5%, and 30.0%, respectively. Age is the most important factor that influences the location of the TZ. The proportion of TZ3 steadily increased with age, comprising over 55% in women over 50. The colposcopic diagnostic performance shows that high-grade squamous intraepithelial lesion or worse (HSIL+) sensitivity of TZ3 (58.1%, 95% confidence interval [CI] = 52.9–63.4) is significantly lower than that of TZ1 (69.8%, 95% CI = 65.5–74.1) and TZ2 (73.2%, 95% CI = 69.7–76.8). The HSIL+ specificity of TZ3 (96.3, 95% CI = 95.3–97.4) was higher than that of TZ1 (96.3, 95% CI = 95.2–97.3) and TZ2 (92.5, 95% CI = 91.1–93.9). The HSIL+ positive predictive value (81.3%, 95% CI = 76.4–86.2) and negative predictive value (89.3%, 95% CI = 87.6–90.9) for TZ3 are high, with no significant differences when compared with TZ1 and TZ2. Conclusions Age predominantly influences TZ location, with TZ3 being most frequently found in women over 50. While TZ3 poses a higher risk of missed diagnosis during colposcopy, it remains clinically valuable in identifying diseased and nondiseased status. Increasing colposcopists' awareness of TZ importance is needed in clinical practice.

Female Genital Tract Melanoma: 10 Years of Experience at a Single Tertiary Center

Objective Malignant melanoma of the female genital tract is a rare disease with poor prognosis, with controversies remaining in its staging and management. In this study, we investigate clinical, pathological, and outcome data for patients referred to a tertiary cancer center with female genital tract melanoma over a decade. Methods Patients were retrospectively identified using a search of pathology reports to identify all cases of female genital tract melanoma from 2007 to 2019. Electronic patient records were used to record clinical information. Histopathology specimens were reviewed by a gynecological and dermatological pathology specialist. Results We identified 30 cases of genital tract melanoma, of which 19 were vulvar, 10 were vaginal, and 1 cervical. Overall survival at 1, 3, and 5 years was found to be 80%, 60%, and 57%. Patients who died were not significantly older at presentation than patients who survived (62 y vs 69 y, p = .215). No association was found between mortality and microscopic ulceration, lymphovascular invasion, pigmentation, resection margins, or radical versus local surgery. Nonvulvar lesions were significantly associated with mortality compared with vulvar lesions (p = .0018), despite similar age and Breslow thickness. Five patients were diagnosed at in situ stage, all of these were vulvar. Even after excluding these melanomas in situ, nonvulvar melanomas still had a significantly worse mortality rate (p = .048). A higher proportion of nonvulvar lesions than vulvar lesions displayed loss of pigmentation (p = .026). Conclusions Nonvulvar genital tract melanomas carry a significantly worse prognosis. Survival was not related to resection margins, supporting the use of more conservative surgical margins.

Clinical Characteristics and Long-Term Follow-up of Patients Treated for High-Grade Vaginal Intraepithelial Neoplasia: Results From a 20-Year Survey in Italy

Objectives The aim of this survey was to evaluate the different surgical approaches for women with high-grade vaginal intraepithelial neoplasia (HG-VaIN) used in 8 hospitals in central and northern Italy in the last 20 years. In particular, the baseline characteristics of the patients and factors potentially leading to excisional treatment rather than ablation were considered. Moreover, the clinical outcome of patients treated for HG-VaIN (disease persistence or recurrence and progression toward invasive vaginal cancer) was analyzed. Materials and Methods The medical records of all women initially diagnosed with HG-VaIN and subsequently treated in 8 Italian hospitals from January 1996 to December 2016 were analyzed in a multicenter retrospective case series. Results Among the 226 women included, 116 (51.3%) underwent ablative procedures and 110 underwent excisional surgery (48.7%). An ablative procedure was preferred in cases where multiple lesions were found on colposcopic examinations. Physicians decided more frequently to perform excisional procedures in women with menopausal status, high-grade referral cervical cytology, previous hysterectomy for human papillomavirus–related disease, or VaIN 3 on colposcopic-guided biopsy. Conclusions The surgical treatment of HG-VaIN should be tailored according to the clinical characteristics of each woman and each lesion. However, in potentially high-risk cases (VaIN 3, previous hysterectomy for human papillomavirus–related disease, and menopausal women) or in those cases in which an occult invasive disease cannot be ruled out, an excisional approach should be preferred. In any case, long-term follow-up is advisable in women treated for HG-VaIN.

Vaginal Intraepithelial Neoplasia: A Retrospective Study of Treatment and Outcomes Among a Cohort of UK Women

Objectives The aim of the study was to analyze the clinical features of women found to have vaginal intraepithelial neoplasia (VaIN), the treatment modalities that they were offered, and clinical outcomes after treatment and follow-up. Materials and Methods This is a retrospective review of all cases of biopsy-proven or treated VaIN occurring for a 15-year period at Southend University Hospital, United Kingdom. Results Eighty-eight cases of VaIN were identified. The age range was from 24 to 76 years, and 39% of cases were low grade (VaIN 1) and 60% high grade (VaIN 2 and 3). Sixty-five percent of patients had either already undergone or would go on to have treatment for cervical intraepithelial neoplasia. Of those with low-grade disease, 86% were managed conservatively with a 97% success rate. Similarly, with high-grade disease, 77% were managed with laser treatment with a success rate of 76% for primary treatment. Of the 6 cases of high-grade disease treated conservatively, 50% subsequently needed active treatment. There was 1 case of progression to vaginal cancer (1.3%). Conclusions Vaginal intraepithelial neoplasia remains an uncommon premalignant condition. It can affect women of all ages and is commoner in those who are immunosuppressed. Observation of low-grade disease is safe and the abnormality often resolves spontaneously. For persistent disease or higher-grade abnormalities, there are many treatment options but laser vaporization is the most commonly used. However, because of the nature of VaIN, recurrence is common even after treatment and further management can be challenging. The overall rate of malignant progression is small but protracted follow-up may be necessary.

Evaluation of a Self-collected Device for Human Papillomavirus Screening to Increase Cervical Cancer Screening

Objective The authors compared the performance of a novel self-collect device with clinician-collected samples for detection of high-risk human papillomavirus (hrHPV). Materials and Methods Eighty-two (82) participants were recruited from 5 clinical sites in the United States. Each participant performed self-collect sampling using the self-collect device followed by a standard of care clinician-collected sample. Both samples were evaluated for hrHPV using polymerase chain reaction (PCR)-based HPV assays. A subset of HPV-positive samples underwent dual staining (p16/Ki-67), and concordance was evaluated. Biopsy results collected per standard of care were recorded. Results On the Roche cobas assay, the preliminary positive percent agreement (PPA) and negative percent agreement (NPA) was 91%. Agreement for hrHPV using the BD OnClarity in PreservCyt was 100% PPA (n = 10), and 100% PPA, 93% NPA in SurePath. Dual-stain concordance was 93% (n = 16) overall, and 100% for HPV other genotypes. Seventy-one participants (n = 71; 89%) indicated they would feel confident using the self-collect device for screening if they knew they could get equal results, and 86% (n = 69) indicated that they would be more likely to get screened with this option. Conclusions The self-collect device shows high (>92%) positive and negative agreement for detection of HPV when compared with reference clinician-collected samples, with very high acceptability and preference. Furthermore, the self-samples collected with the self-collect device showed highly concordant results by dual stain, which is a novel and emerging application for a self-collected sampling device, thus enabling potential triage from 1 sample.

Cervical Stenosis: Previously Unrecognized Cause of False-Negative Human Papillomavirus Tests in Women Developing Cervical Cancer

ObjectivesCervical stenosis can jeopardize adequate posttreatment cytologic follow-up of patients treated for high-grade cervical intraepithelial lesions. An impact on human papillomavirus (HPV) testing has not been described.Materials and MethodsWe describe 2 patients with cervical stenosis, followed by cytology and HPV co-testing after excisions of high-grade cervical intraepithelial lesions. Each had 1 or more co-test “double-negative” results. Hysterectomies revealed unexpected cervical carcinomas.ResultsIn case 1, an 80-year-old woman with complete cervical stenosis and earlier high-grade squamous dysplasia presented with abdominal pain, nausea, and an enlarged uterus. Attempted endometrial biopsy was unsuccessful. Cytology and HPV tests 9 months earlier were negative. Hysterectomy revealed a cervical squamous carcinoma. In case 2, a 40-year-old woman followed conservatively after excision of endocervical adenocarcinoma in situ had 5 follow-up cytology and HPV co-tests. All were HPV negative. Elective hysterectomy revealed cervical adenocarcinoma. Both carcinomas tested HPV positive.ConclusionsCervical stenosis in women developing cervical cancer can cause misleading sampling and false-negative HPV test results.

The Role of Cervical or Vaginal HPV Testing in Surveillance of Vulvar, Vaginal, and Anal HPV-Associated Neoplasia

Objectives The study aims are to evaluate the utility of cervical or vaginal human papillomavirus (HPV) status in predicting recurrence of noncervix lower genital tract (LGT) high-grade squamous intraepithelial lesion (HSIL), assess factors associated with HPV positivity, and explore patterns of HSIL surveillance. Methods This retrospective cohort included patients undergoing ≥12 months of surveillance after biopsy-proven vulvar, vaginal, or anal HSIL between 2015 and 2023 at an Australian hospital with a laboratory that performs universal p16 and p53 immunohistochemistry for vulvar squamous neoplasia. Data collected included demographics, HPV results, medical comorbidities, vulvar dermatoses, treatment, frequency of surveillance, outcomes, and follow-up duration. Data were stratified by HPV status at the time of LGT HSIL diagnosis. Results Of 143 patients with a median age of 54 years, 23% used topical steroids for lichen sclerosus or planus, 93% had a recent or concurrent HPV test, and 53% of these were positive. Positive HPV was more frequent in vaginal versus vulvar HSIL (92% vs 46%; p = .003) and less frequent in patients with diabetes (23% vs 3%; p < .001). Recurrent or persistent HSIL occurred in 65%. HPV positivity was not associated with overall recurrence, but afforded a 6-fold higher vaginal HSIL recurrence risk. There was a documented surveillance strategy in 92% with 78% of these having 6-monthly assessments for 5 disease-free years, then annually. Conclusions Cervical or vaginal oncogenic HPV results do not predict vulvar HSIL recurrence but may inform surveillance for vaginal disease. Limitations include the retrospective design, potential referral bias, and limited generalizability.

Assessing Physician Adherence to Guidelines for CervicalCancer Screening and Management of AbnormalScreening Results

Objective The aim of the study was to survey obstetrician-gynecologists' cervical cancer screening practices and management of cervical abnormalities to ascertain adherence to guidelines. Methods From January to July 2019, obstetrician-gynecologists at 5 St. Louis area hospitals were surveyed online about cervical cancer screening and management practices through 13 clinical vignettes. Survey scores and the American Society of Colposcopy and Cervical Pathology (ASCCP) app use were compared using Mann-Whitney tests. Results When screening 30- to 65-year-old participants, 114 (98%) of the 116 total participants used co-testing, but only 71 (61%) screened at 5-year intervals. None used primary human papillomavirus (HPV) testing. For 21- to 29-year-old participants, 17 (15%) screened with annual cytology, whereas 14 (12%) used annual or every 3-year co-testing. Forty eight (41%) screened younger than 21 years, regardless of risk factors or only if immunocompromised. Eleven (9%) continued screening after total hysterectomy for benign indications. Only 2 (2%) responded to all clinical vignettes in adherence to guidelines. More than 30% of participants would pursue unnecessary HPV testing and/or loop electrosurgical excision procedure for persistent low-grade cytology. Fifty eight (48%) incorrectly reported hysterectomy as management for adenocarcinoma in situ on biopsy. Participants would undertreat young women with high-grade abnormalities including high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia 3 (48, 41%) and high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia 1 (65, 56%). Forty one (35%) reported exiting women from screening prematurely. The median score for participants using the ASCCP app was significantly greater than those who did not (79% vs 71%, p = .002). Conclusions Midwestern obstetrician-gynecologists' adherence to the guidelines for cervical cancer screening and management of abnormal results is suboptimal. Although co-testing for women aged 30–65 years has been broadly adopted, primary HPV testing has not. Physicians overscreen, overtreat low-grade lesions, and undertreat high-grade lesions in young women.

Effect of Obesity on Cervical Cancer Screening and Outcomes

Objectives The aims of the study were to identify whether obese women are less appropriately screened for cervical cancer before diagnosis and to explore related cancer outcomes. Methods We retrospectively reviewed all cervical cancer patients at a single institution between 1986 and 2016 and collected demographic information including age, cancer stage, body mass index (BMI), screening information, and cancer outcomes. Morbid obesity was defined as BMI of 40 kg/m2 or greater, obesity as BMI of 30 to less than 40 kg/m2, and nonobese as BMI of less than 30 kg/m2. χ2, Fisher exact, and Wilcoxon rank sum tests were used to compare variables between BMI categories. Cox regression models were used to evaluate recurrence-free survival and overall survival (OS). Results A total of 1,080 patients were reviewed, of whom 311 (29.4%) were obese and 107 (10.1%) morbidly obese. A significant association between BMI and cytology screening was evidenced with morbidly obese women having the highest incorrect rate (64.4%), followed by obese (51.5%) and nonobese women (46.0%, p < .01). There was no significant difference in presence of symptoms at presentation (p = .12) or stage (p = .06) between BMI categories. In multivariable analysis of cancer outcomes, higher BMI was associated with worse OS (p < .01) with a hazard ratio of 1.25 (95% CI = 0.92–1.69) for obese women and hazard ratio 2.27 (95% CI = 1.56–3.31) for morbidly obese women relative to normal weight but recurrence-free survival did not differ between BMI groups (p = .07). Conclusions Our study strengthens evidence that obese and morbidly obese women have disproportionate inappropriate screening before cervical cancer diagnosis, and morbidly obese women have worse OS than their counterparts.

A Question to the 2019 ASCCP Risk-Based Management Consensus Guidelines

Response to Letter to the Editor Regarding: 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors

Is There a Place for the Introduction of Colposcopy Quality Standards?

Objectives The aims of the study were to examine the degree of compliance with international quality measures for colposcopy in Israel, which does not currently have formal guidelines and to compare the achievement of quality measures between clinical settings. Methods This is a retrospective cohort study, in a hospital, a community clinic, and 2 private colposcopy clinics in Israel, including women aged 18–70 years presenting for colposcopy after abnormal Pap results. Compliance was compared between clinical sites regarding 6 international standards: documentation of reason for referral, type of transformation zone, biopsy location, and grade; proportion of women with high-degree cytological abnormalities (atypical squamous cells - cannot exclude high grade squamous intraepithelial lesion and above) receiving a colposcopy within 4 weeks; and the positive predictive value of colposcopy to detect cervical intraepithelial neoplasia 2 and above. Results Documentation of reason for referral (1.3% of target), transformation zone type (22.6% of target), biopsy location (18% of target), and lesion grade (31% of target) all failed to meet international standards, as did the proportion of patients with high-degree cytological abnormalities who underwent colposcopy within 4 weeks (32.9% of the target). The positive predictive value of colposcopy exceeded standards (30% above target). Differences existed between clinical settings. Conclusions In Israel, there is a considerable shortfall in performance and documentation of most international quality measures for colposcopy. Quality measures for cervical examinations and colposcopy should be considered for inclusion in the National Program for Quality Measures.

P16/Ki-67 Immunostaining in the Triage of Postmenopausal Women With Low-Grade Cytology Results

Objective The interpretation of postmenopausal smears and the gynecological treatment of these patients can often be difficult. The objective of this study was to assess the performance of p16/Ki-67 dual-stained cytology as a triage of atypical squamous cells of undetermined significance and low-grade intraepithelial lesion cytology results in postmenopausal women. Methods All consecutive atypical squamous cells of undetermined significance and low-grade intraepithelial lesion smears in 1-year period were collected and p16/Ki-67 immunostaining was performed retrospectively. The results were compared with histology results or long-term cytology follow-up in cases with no biopsy. Results The sensitivity of p16/Ki-67 immunostaining for the detection of cervical intraepithelial neoplasia (CIN) 2 and CIN 3 was 57.1% and 85.0%, respectively. The specificity for the detection of CIN 2 was 94.3% and CIN 3 92.4%. Negative predictive values for the detection of CIN 2 and CIN 3 were 96.3% and 99.6%, respectively. Conclusions Dual p16/Ki-67 immunostaining is a useful additional method in postmenopausal patients with low-grade cytology. Considering the high specificity and negative predictive value in our study, we believe that it could be helpful in avoiding unnecessary referrals to colposcopy and thus reduce the cost of the program.

HPV Catch-up Vaccination Reduces the Prevalence of HPV 16 and 18 Infections and Cervical Disease: A Retrospective Study

Differences Between Squamous Intraepithelial Lesions of the Vulva and the Cervix

Abstract The Lower Anogenital Squamous Terminology project and subsequent publication have grouped preinvasive human papillomavirus–associated squamous intraepithelial lesions of the lower genital tract and adjacent skin as a single entity. We are concerned that as a result of this grouping, some of the clinically relevant differences may not be taken into consideration. We describe differences between high-grade squamous intraepithelial lesion of the vulva and cervix (vulvar intraepithelial neoplasia and cervical intraepithelial neoplasia), in embryology (arising from ectoderm vs mesoderm), clinical presentations (symptoms or signs due to many vulvar lesions vs abnormal cytology), examination techniques and diagnosis (clinical examination of potentially widely involved areas vs colposcopy of the transformation zone), natural history, management, and follow-up requirements (long-term clinical assessment vs cytology and human papillomavirus testing). We believe that failure to understand these important differences will lead to errors in management.

2019 ASCCP Risk-Based Management Consensus Guidelines: Methods for Risk Estimation, Recommended Management, and Validation

Objective To manage cervical screening abnormalities, the 2019 ASCCP management consensus guidelines will recommend clinical action on the basis of risk of cervical precancer and cancer. This article details the methods used to estimate risk, to determine the risk-based management, and to validate that the risk-based recommendations are of general use in different settings. Methods Based on 1.5 million patients undergoing triennial cervical screening by cotesting at the Kaiser Permanente Northern California from 2003 to 2017, we estimated risk profiles for different clinical scenarios and combinations of past and current human papillomavirus and cytology test results. We validated the recommended management by comparing with the estimated risks in several external data sources. Results Risk and management tables are presented separately by Egemen et al. 1 and Demarco et al. 2 Risk-based management derived from the Kaiser Permanente Northern California largely agreed with the management implied from the estimated risks of the other data sources. Conclusions The new risk-based guidelines present management of abnormal cervical screening results. By describing the steps used to develop these guidelines, the methods presented in this article can provide a basis for future extensions of the risk-based guidelines.

Risk of Recurrence After Treatment for Cervical Intraepithelial Neoplasia 3 and Adenocarcinoma In Situ of the Cervix: Recurrence of CIN 3 and AIS of Cervix

Objectives The aim of the study was to evaluate recurrence risk of cervical intraepithelial neoplasia (CIN) 3+ and adenocarcinoma in situ (AIS)+ in a large population cohort of women previously treated for CIN 3/AIS. Methods Merging administrative databases with information on health services utilization and jurisdictional cancer registry, we identified all women undergoing treatment for CIN 3 or AIS from 2006 to 2010. Recurrence rate 1–5 years after treatment was defined as a biopsy finding of CIN 3/AIS or retreatment (loop electrosurgical excision procedure [LEEP], laser, cone, hysterectomy). Logistic regression was used to determine odds of recurrence. Results A total of 15,177 women underwent treatment for CIN 3 (n = 14,668) and AIS (n = 509). The recurrence rate for 5 years was greater for AIS (9.0%) compared with CIN 3 (6.1%). In a multivariate analysis, increased risk of recurrence was shown for age older than 45 years (hazard ratio (HR) = 1.3, 95% CI = 1.1–1.6), AIS compared with CIN 3 (HR = 2.2, 95% CI = 1.5–3.5) first cytology after treatment showing high grade (HR = 12.4, 95% CI = 9.7–15.7), and no normal Pap smears after treatment (HR = 2.8, 95% CI = 2.2–3.7). There was no difference in recurrence risk with treatment type (cone vs LEEP: HR = 1.0, 95% CI = 0.8–1.2, and laser vs LEEP: HR = 1.1, 95% CI = 0.8–1.4) or number of procedures per year performed by physicians (<40 vs >40 procedures: HR = 1.1, 95% CI = 0.9–1.3). Conclusions Recurrence risk of CIN 3 and AIS is related to age, histology, and posttreatment cytology, which should assist with discharge planning from colposcopy. Definitive treatment with hysterectomy should be considered in women older than 45 years with additional risk factors for recurrence.

Cervical Stratified Mucin-Producing Intraepithelial Lesion: A Systematic Review of Diagnosis and Management

Objectives The aims of the study were to synthesize reported associations of stratified mucin-producing intraepithelial lesion (SMILE) of the cervix with other dysplasia lesions and immunohistochemical (IHC) stains, compare expected patterns of IHC staining to other lesions in the differential diagnosis, and assess follow-up pathology. Methods This systematic review includes all case reports and case series of cervical lesions consistent with SMILE based on the histologic diagnosis described in the original case series. MEDLINE, EMBASE, and Cochrane Database were searched through June 2019. Immunohistochemical analysis, concurrent lesions, and pathology on follow-up were compiled for comparison. Weighted averages of concurrent lesions were calculated. Results Nine case reports and case series were included, published between 2000 and 2019. Of 9 studies, 6 and 5 studies reported strong, diffuse staining of p16 and increased expression of Ki-67, respectively. Stratified mucin-producing intraepithelial lesion is associated with human papillomavirus, especially type 18. The weighted average risk of concurrent high-grade squamous intraepithelial lesion was 79% (range = 33%–93%), adenocarcinoma in situ 39% (2.9%–92%), adenocarcinoma 5% (1%–25%), and squamous cell carcinoma 6% (0%–11%). Patients underwent follow-up ranging from repeat Pap to radical hysterectomy, with pathology on follow-up infrequently and irregularly reported. Conclusions Stratified mucin-producing intraepithelial lesion is a rare lesion with a paucity of research on necessary cytology and IHC stains for diagnosis, but p16 and Ki-67 IHC stains can be performed to rule out benign lesions. The lesion is associated with high risk of concurrent high-grade squamous intraepithelial lesion, adenocarcinoma in situ, and invasive carcinoma, but studies on the risk of pursuing fertility-preserving management are needed.

2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors

Loop Electrosurgical Excision Procedure or Cervical Conization to Exclude Cervical Cancer Before Simple Hysterectomy

Objective The aim of the study was to determine which women require loop electrosurgical excision procedure (LEEP) or cervical conization (cone) to exclude cervical cancer after colposcopy for evaluation of abnormal cervical cancer screening tests yet before simple hysterectomy. Materials and Methods Review of electronic medical records from colposcopy clinics followed by chart review of women with cervical cancer was conducted. Results Of 18,537 cervical colposcopies for evaluation of abnormal cervical cancer screening tests, 0.6% (103/18,537) had cervical cancer; of 103 women with cervical cancer, 57 had neither cervical biopsy nor endocervical curettage (ECC) showing cancer or rule-out cancer (occult cancers) and were diagnosed by subsequent LEEP (n = 22), cone (n = 31), failed cone (n = 1), or hysterectomy (n = 3). The relative risk of occult cervical cancer at colposcopy for ECC of cervical intraepithelial neoplasia (CIN) 2 or CIN 3 versus ECC not CIN 2 or CIN 3 was 51.5 (5.0% vs 0.1%), for cervical biopsy of CIN 3 versus not CIN 3, was 34.5 (3.9% vs 0.1%), and for colposcopic impression of CIN 2, CIN 3, or cancer (CIN 2+) versus impression not CIN 2+, was 8.5 (1.9% vs 0.2%). If the 10.9% (2,018/18,537) of colposcopies with ECC of CIN 2 or CIN 3, cervical biopsy of CIN 3, or colposcopic impression of CIN 2+ had subsequent LEEP or cone, 96.5% (55/57) of occult cervical cancers would be detected before hysterectomy. Conclusions After colposcopy, women with ECC of CIN 2 or CIN 3, cervical biopsy of CIN 3, or colposcopic impression of CIN 2+ require LEEP or cone before simple hysterectomy.

Trends in Patient Demographics and Diagnostic Yield at an Academic Colposcopy Clinic From 2008 to 2018

Objective The aim of the study was to review trends in colposcopy rates and diagnoses of high-grade dysplasia and cancer for the past 10 years at an academic colposcopy clinic. Materials and Methods A registry of patients seen January 2008 to December 2018 at an academic colposcopy clinic was queried to examine trends in patient characteristics, cytology and histology results, and interventions during the study period, which coincided with the implementation of revised national guidelines. Differences in characteristics were examined with analysis of variance and χ2 tests. Trends in diagnoses were examined with logistic regression. Trends in interventions were modeled with binomial distribution, logit link, Poisson distribution, and log link. Results Among 5,103 women referred for abnormal pap testing, human papillomavirus, or dysplasia, the mean age increased over time (30.6 in 2008 to 38.4 in 2018, p < .0001) and fewer pregnant patients were served (11.3% in 2008 vs 2.8% in 2018, p < .0001). There were decreased rates of low-grade cytology (81.3% in 2008 vs 73.6% in 2018, p = .006) and increased rates of human papillomavirus positivity (4.1% in 2008 vs. 14.4% in 2018, p < .0001) on referral. Fewer colposcopies were performed per patient per year (1.2 in 2008 vs. 0.7 in 2018, p < .0001), and with this targeted intervention, there was an increased percentage of patients diagnosed with high-grade histology over time (adjusted p = .05). Conclusions Over time, the number of colposcopies performed per patient decreased, especially in younger and pregnant women. Meanwhile, the percentage of patients diagnosed with high-grade histology increased, suggesting that guidelines decreased unnecessary procedures while increasing the percentage of patients diagnosed with precancerous lesions.

Challenges Associated With Cervical Cancer Screening and Management in Obese Women: A Provider Perspective

Objectives Obese women are at increased risk of cervical cancer, partly due to missed detection of cervical precancers during routine cervical cancer screening. We administered a clinician survey to better understand specific challenges and identify potential solutions to performing cervical cancer screening and management in obese women. Materials and Methods We administered a web-based survey to 2,319 members of the American Society of Colposcopy and Cervical Pathology including questions related to challenges associated with cervical sampling and visualization in obese compared with normal weight women and potential strategies for improvement. We summarized providers' responses using descriptive statistics and used Fisher exact tests to evaluate associations between provider characteristics and challenges with cervical sampling, visualization, and biopsy. Results Of the 240 providers that completed the survey, 89% and 93% reported that cervical sampling and visualization are more challenging in obese women, respectively, whereas 80% reported that taking a biopsy was more challenging. Commonly reported barriers included vaginal prolapse, difficulty visualizing and accessing the cervix, and lack of long enough sampling devices and large enough speculums. Frequently used techniques to improve sampling and visualization included use of a condom or examination glove finger to sheath a speculum and using a tenaculum. Most providers identified training for cervical sampling and colposcopy in obese women as a learning gap, and only 8% reported receiving such training. Conclusions Cervical cancer screening and management are more challenging in obese compared with normal weight women. Major barriers to cervical sampling and visualization included lack of adequately sized equipment and lack of education and training.

Role of Oral Tramadol 50 mg in Reducing Pain During Colposcopy-Directed Cervical Biopsy: A Randomized Controlled Trial

Objective The aim of the study was to assess safety and efficacy of 50-mg tramadol in reducing patient-perceived pain during colposcopy. Material and Methods We conducted a randomized double-blind placebo-controlled trial in the colposcopy unit of a tertiary referral hospital, Cairo, Egypt, from April 2018 to October 2018. Our primary outcome was pain during colposcopy-guided ectocervical punch biopsy. Our secondary outcomes were pain during speculum insertion, acetic acid application, Lugol iodine application, endocervical curettage (ECC), endocervical brushing, 10-minute postprocedure, and additional analgesia requirement. Pain was assessed using 10-cm visual analog scale. Results One hundred fifty women were randomized into 2 groups: tramadol group (n = 75) received oral 50-mg tramadol tablets, and control group (n = 75) received placebo tablets. Both groups showed no significant difference in anticipated pain score (p = .56), pain scores during speculum insertion (p = .70), application of acetic acid (p = .40), and Lugol iodine (p = .79). However, the mean pain scores were significantly lower in tramadol group compared with placebo at ectocervical biopsy (p = .001), ECC (p = .001), endocervical brushing (p = .001), and 10 minutes after colposcopy (p = .001). Need for additional analgesia was significantly lower in tramadol group (p = .03). Conclusions Oral tramadol 50 mg significantly reduces pain perception during colposcopy-guided ectocervical biopsy, ECC, endocervical brushing, and 10 minutes after colposcopy with tolerable adverse effects.

High-Risk Human Papillomavirus Identification in Precancerous Cervical Intraepithelial Lesions

Objective This review aims to summarize the currently available human papillomavirus (HPV) testing methods for precancerous cervical intraepithelial lesions. Materials and Methods A literature search of PubMed using key words “high-risk HPV, precancerous cervical intraepithelial lesions, FDA-approved HPV tests, p16 IHC, Ki 67 IHC, fluorescent in situ hybridization for HPV, Pap smear, HPV vaccines, HPV tests using self-collected samples, and next-generation sequencing” was performed between January 1 and June 14, 2019. The package inserts of the Food and Drug Administration–approved HPV tests were obtained from the companies' Web sites. Results Multiple morphology-based, immunohistochemical staining and nucleic acid HPV tests were reviewed, including the material required, methodologies, result interpretations, as well as their advantages, limitations, and futures. The structure of HPV and its natural history of infection and transmission were touched on as well for a better understanding of these testing methods. Conclusions Human papillomavirus tests are a critical component for cervical cancer screening, and understanding of these tests helps test results interpretation and patients' triage.

Association of Body Mass Index With Adherence to Cervical Cancer Screening Recommendations in Hispanic Women

Objective Obese women have higher cervical cancer incidence and mortality than their counterparts, possibly related to nonadherence to screening recommendations. We assessed the association of body mass index with adherence to cervical cancer screening recommendations in Hispanic women living in Puerto Rico, a minority population with the highest incidence of cervical cancer in the United States. Materials and Methods We included 536 Hispanic women aged 21 to 64 years enrolled in a population-based study of human papillomavirus (HPV) infection. Demographic and clinical characteristics and risky behaviors were collected using structured interviews. Weight and height were measured to classify body mass index as underweight, normal, overweight, and obesity (class I, class II, class III). Adherence to cervical cancer screening recommendations was self-reported. Logistic regression models were fit to estimate the odds ratio with 95% CI after adjusting for covariates. Results Nearly one third (29.7%) of women were overweight and 43.5% were obese (class I: 22.6%, class II: 11.0%, class III: 9.9%). Overall adherence to cervical cancer screening within the past 3 years was 78.5%, being lowest among women with class III obesity (60.4%). After multivariable adjustment, only women with class III obesity had significantly higher odds (odds ratio = 2.5, 95% CI: 1.2–5.1) of reporting nonadherence to cervical cancer screening compared with normal weight women. Conclusions Adherence to cervical cancer screening in this population was below the Healthy People 2020 target of 93%, especially for women with morbid obesity. These findings highlight the importance of adequate interventions to decrease cervical cancer screening disparities in these women.

Specimen Fragmentation and Loop Electrosurgical Excision Procedure and Cold Knife Cone Biopsy Outcomes

Objective Surgical technique for loop electrosurgical excision procedure (LEEP) and cold knife cone (CKC) emphasizes a uniform specimen, but sequelae of specimen fragmentation are not established. We evaluated outcomes between fragmented and unfragmented excisional biopsy specimens. Materials and Methods Loop electrosurgical excision procedure and CKCs from January 2010 to October 2013 were reviewed. Intraepithelial lesion grade, fragmentation, margin, and Endocervical curettage status were analyzed. Adenocarcinoma in situ and cancer were excluded. Repeat procedures during the study period were included in follow-up. Loop electrosurgical excision procedures with top hat with no separate fragments were analyzed independently versus those with fragmented LEEP and/or top hat. Indeterminate margin was defined as inconclusive or unevaluable margin, or intraepithelial lesion in unidentifiable margin or fragment. Outcomes involved residual or recurrent disease and repeat procedures for intraepithelial lesion. χ2 was used for statistical analysis. Results Fragmented specimens were more likely to have any positive margin (p = .01), multiple positive margins (p < .001), and indeterminate margin (p < .001) than unfragmented specimens. There was no significant difference in rates of positive, insufficient, or high-grade Endocervical curettage (p = .74, 0.54, 0.92). Patients with fragmented specimens were more likely to have high-grade lesion recurrence in the following 3 years (p = .04) versus patients with index unfragmented specimens, though not compared with those with unfragmented LEEP + top-hat cases. Overall rates of repeat LEEP/CKC or hysterectomy for dysplasia were not different (p = .56). Conclusions Fragmentation of LEEP and CKC specimens is associated with higher rates of positive margins, recurrent high-grade intraepithelial lesions, and indeterminate margins. These may cause diagnostic uncertainty, require closer follow-up, and increase cost with more visits and studies.

Loop Electrosurgical Excision Procedure Treats Cervical Intraepithelial Neoplasia 2/3 Among HIV− and HIV+ Women in Kenya

Objective The aim of the study was to compare loop electrosurgical excision procedure (LEEP) as treatment for cervical intraepithelial neoplasia (CIN) 2/3 in HIV− versus HIV+ women. Materials and Methods Seventy-five HIV− and 75 HIV+ women at 6 months or more after LEEP for CIN 2/3 were enrolled between September 2013 and November 2014 in this prospective cohort study at the cervical cancer screening clinic in Eldoret, Kenya. Visual inspection with acetic acid (VIA), followed by cervical cytology with conventional cytology, was performed on all women. Women with positive VIA or abnormal cervical cytology underwent colposcopy/biopsy. Lesion progression, persistence, and regression were assessed to quantify the efficacy of LEEP. Results Post–loop electrosurgical excision procedure screening test showed both a negative VIA and normal cervical cytology in 64 (85%) of HIV− and 57 (77%) HIV+ women (risk difference = 8.3%, CI = −4.2% to 21%, p = .20). Eleven (15%) HIV− and 17 (23%) HIV+ ( p = .20) women had positive VIA, abnormal cervical cytology, or both and were referred for colposcopy/biopsy. Twenty-one (8 HIV−, 13 HIV+) women were biopsied. Of the 8 HIV− women, 4 (50%) had CIN lesions that regressed, 3 (38.0%) persisted, and 1 (12%) progressed to invasive cancer after LEEP. Of the 13 HIV+ women, 6 (46%) had CIN lesions that regressed, 7 (54%) had CIN lesions that persisted, and no HIV+ women had CIN lesions that progressed after LEEP. There was no difference in estimated efficacies of LEEP for HIV− and HIV+ women (92.7% versus 89.4%, risk difference = 3.3%, CI = −4.8% to 15.3%, p = .85). Conclusions Loop electrosurgical excision procedure for CIN 2/3 is effective treatment for HIV− and HIV+ women in low-resource settings. Future efforts should improve follow-up after treatment.

Molecular Features of Preinvasive and Invasive Vulvar Neoplasms

Objectives Neoplasms arising from the vulva are uncommon and comprise various subtypes. Given the recent advancements in the molecular aspects of oncologic pathology and how they have impacted cancer treatment, an understanding of recent innovations in the molecular features of vulvar lesions is important. Materials and Methods Systematic literature search was performed on PubMed, Google Scholar, and Scopus databases for molecular and genetic characteristics of vulvar neoplasms. Peer-reviewed literature published in English is included. Results Squamous cell carcinoma (SCC) and its precursors are the predominant neoplasm at this site. Human papillomavirus (HPV) plays a crucial role in the pathogenesis of some of these lesions. Human papillomavirus–associated SCC follows the carcinogenic pathway driven by viral proteins E6 and E7 while HPV-independent SCC shows a high incidence of mutation of TP53 and CDKN2A genes. Mutations in the genes involving the PI3K-Akt pathway play an important role in the pathogenesis of both types of SCC. Among other vulvar malignancies, melanoma, and vulvar Paget disease (VPD) pose a significant clinical challenge and have unique molecular characteristics. Compared with dermal cutaneous melanoma, vulvar melanoma shows a higher rate of mutation of cKIT and NRAS genes and a lower rate of mutations in BRAF. Less than 20% of VPD shows amplification of ERBB2 and seldom shows mutation in genes involving the PI3K-Akt pathway. Conclusions Several potentially targetable molecular pathways have emerged as they have been shown to be involved in the tumorigenesis of SCC, melanoma, and VPD.

Incidence and Risk Factors for Recurrence and Progression of HPV–Independent Vulvar Intraepithelial Neoplasia

Objectives Human papillomavirus (HPV)–independent vulvar intraepithelial neoplasia (VIN) is a rare yet aggressive precursor lesion of vulvar cancer. Our objectives were to estimate its long-term incidence, the risk of recurrent disease and progression to vulvar cancer, and risk factors thereof. Materials and Methods Patients with HPV-independent VIN between 1991 and 2019 in a selected region were identified from the Dutch Nationwide Pathology Databank (Palga). Data were collected from the pathology reports. Crude and European age-standardized incidence rates were calculated for 10-year periods. Kaplan-Meier analyses were performed to determine the cumulative recurrence and cancer incidence, followed by Cox regression analyses to identify associated risk factors. Results A total of 114 patients were diagnosed with solitary HPV-independent VIN without prior or concurrent vulvar cancer. The European age-standardized incidence rate increased from 0.09 to 0.69 per 100,000 women-years between 1991–2010 and 2011–2019. A cumulative recurrence and cancer incidence of 29% and 46% were found after 8 and 13 years of follow-up, respectively. Nonradical surgery was identified as the only independent risk factor for recurrent HPV-independent VIN. Risk factors associated with progression to cancer were increasing age and a mutant p53 immunohistochemical staining pattern. Conclusions The incidence of detected HPV-independent VIN has substantially increased the last decade and the subsequent recurrence and vulvar cancer risks are high. Although HPV-independent VIN may present as a wide morphologic spectrum, surgical treatment should aim for negative resection margins followed by close surveillance, especially for p53 mutant lesions.

Syringocystadenoma Papilliferum of the Vulva: An Extremely Rare Vulvar Tumor

Aesthetic Outcome and Psychosexual Distress After Treatment for Vulvar High-Grade Squamous Intraepithelial Lesions

Objectives This study compared aesthetic outcome, psychosexual distress, and treatment satisfaction between women receiving surgical treatment or medical treatment with imiquimod for vulvar high-grade squamous intraepithelial lesion. Materials and Methods This is an extended analysis of the multicenter, randomized noninferiority trial “topical imiquimod versus surgery for vulvar intraepithelial neoplasia.” Patients were randomized to primary topical treatment or surgery and stratified by unifocal or multifocal disease. Digital photos of vulvar appearance were subsequently assessed for aesthetic outcome by 3 investigators blinded to group allocation. Psychosexual distress and treatment satisfaction were assessed with the Cervical Dysplasia Distress Questionnaire, the Sexual Activity Questionnaire, and the Client Satisfaction Questionnaire at baseline and follow-up. Results One hundred ten patients aged between 19 and 82 years were enrolled. Per-protocol analysis showed complete clinical response in 80% (37/46) using imiquimod, compared with 79% (41/52) after one surgical intervention. Photodocumentation at baseline and 6-month follow-up was available for 84 of these patients (44 imiquimod, 40 surgery). Blinded reviewer assessments of lesion size and lesion severity showed improvement from baseline to follow-up, with no differences between treatment groups. Sexual pleasure, discomfort, and distress remained stable from baseline to follow-up in both groups. Conclusions Good aesthetic outcome of vulvar high-grade squamous intraepithelial lesion treatment can be achieved with imiquimod and surgery, consisting of ablation or local excision. Treatment satisfaction and stable psychosexual health may not be dependent on chosen treatment modality, but rather on counseling in accordance with patients’ preferences.

Multiple Vulvar Polyps in Pregnancy: A Benign Disease With a Challenging Diagnosis

Vulvar High-Grade Squamous Intraepithelial Lesion and the Risk of Recurrence and Progression to Cancer

Objective This study aimed to analyze which clinical characteristics are associated with recurrence and progression of vulvar high-grade squamous intraepithelial lesion (vHSIL). Materials and Methods This was a retrospective cohort study, including all women with vHSIL followed in 1 center between 2009 and 2021. Women with a concomitant diagnosis of invasive vulvar cancer were excluded. Medical records were reviewed for demographic factors, clinical data, treatment type, histopathologic results, and follow-up information. Results A total of 30 women were diagnosed with vHSIL. The median follow-up time was 4 years (range = 1–12 years). More than half of the women (56.7% [17/30]) underwent excisional treatment, whereas 26.7% (8/30) underwent combined (excisional plus medical) treatment, and 16.7% (5/30) only had medical treatment (imiquimod). Six women had recurrence of vHSIL (20% [6/30]), with a mean time to recurrence of 4.7 ± 2.88 years. The progression rate to invasive vulvar cancer was 13.3% (4/30), with a mean time to progression of 1.8 ± 0.96 years. Multifocal disease was associated with progression to vulvar cancer (p = .035). We did not identify other variables associated with progression; no differences were found between women with and without recurrences. Conclusions Multifocality of the lesions was the only variable associated with progression to vulvar cancer. This reinforces the idea that these lesions are a challenge in both treatment and surveillance, involving a more difficult therapeutic decision with greater associated morbidity.

Mass Spectrometry Proteomic Analysis of Four p53 Patterns in Differentiated Vulvar Intraepithelial Neoplasia

Objective The histopathologic diagnostic criteria of differentiated vulvar intraepithelial neoplasia (dVIN), the precursor of human papillomavirus-independent squamous cell carcinoma, are basal atypia, a negative or non–block-positive p16, and a supportive p53 immunohistochemistry (IHC). Several different patterns of supportive p53 IHC have been described. This study aims to determine the relationship between p53 IHC patterns and mass spectrometry analysis of cellular proteins in dVIN. Methods Four patterns of p53 IHC were studied: overexpression, cytoplasmic, wild type, and intermediate expression between wild type and overexpression. For each pattern, tissue samples of 4 examples were subjected to mass spectrometry. Results The protein profile within each p53 IHC pattern shared common features. Each of the 4 p53 patterns had a distinguishable protein profile when compared with the other 3 patterns. Conclusions The distinguishable protein profiles in different p53 IHC patterns suggest diverse mechanisms of TP53 dysfunction. Subtyping dVIN by p53 IHC is worthy of further study because varied protein expression profiles may translate into different clinical behavior.

Identification of Risk Factors of Recurrence Among Patients With Vulvar Paget Disease Treated With Conservative Surgery

Objectives Vulvar Paget disease (VPD) is a benign disease with high recurrence rates. Standard treatment involves conservative surgery with wide local excision of the lesion. The purpose of the present study is to identify factors that increase the risk of relapse. Materials and Methods We conducted a retrospective study and included patients treated with conservative surgery for noninvasive VPD. Cox regression analysis was carried out to assess the independent effect of age, presence of positive margins, tumor size greater than 4 cm, bilateral lesions, and compositive morbidity and pathology on recurrence free survival. Post hoc power analysis was performed with the G-power tool using an α error of 0.05. Results Overall, 39 patients were included with a median age of 70 years (46–85 years). Of those, 19 patients relapsed within a median duration of 30.5 months (5–132 months). Twelve patients (63%) experienced at least a second relapse. The presence of composite comorbidity significantly affected the interval to recurrence (30.09 vs 71.80 months, p = .032). Univariate Cox regression analysis revealed that the presence of composite pathology features was indicative of a higher risk of recurrence (hazard ratio = −3.71, p = .024). The sample size did not allow for adequate power for this latter finding. Microscopically involved tumor margins and tumor size greater than 4 cm did not predict patients at risk of experiencing relapsing disease. Conclusions Patients with noninvasive VPD experience high relapse rates. The presence of concurrent benign vulvar pathology may increase these rates, although larger sample sizes are needed to ascertain our findings.

A Scoping Review of Treatment Outcome Measures for Vulvar Intraepithelial Neoplasia

Objective The goal of this study is to identify a list of clinician-reported outcome measures (CROMs) and patient-reported outcome measures (PROMs) through a review of published studies reporting on any therapeutic interventions for vulvar intraepithelial neoplasia (VIN). Materials and Methods A systematic search of published studies reporting on any therapeutic interventions for VIN was performed on MEDLINE, Embase, Cochrane Database, PsychInfo, and CINAHL from inception to September 20, 2021, based on predetermined study selection criteria. Data were extracted and analyzed by 2 authors independently using Covidence software. Results Thirty two of 2386 studies identified met study selection criteria. None of the 32 studies provided an explicit definition of VIN treatment “success.” The most common CROM was “clinical response to treatment.” The most common scale used to measure this outcome was “complete response/partial response/no response”; however, 17 of 23 studies (73.9%) did not define these values. Laboratory CROMs were reported in 12/32 (37.5%) studies. Patient-reported outcome measures were reported in only 10 of 32 studies(31.3%) —the most common PROM was “symptoms.” Only 2 of 32 studies measured PROMs related to “quality of life” domains. Adverse events/treatment-related adverse effects were reported in 24 of 32 studies (75%), although 71% of studies provided no details on how these data were collected. Conclusions There is a large variation in outcome measures, instruments, and scales used for any clinician-reported treatment outcome such as “clinical response.” Most studies do not include patient-reported outcome measures assessing quality of life domains. A Core Outcome Set for the treatment of VIN is needed to improve the quality of VIN research.

A Systematic Review of Risk Factors for Development, Recurrence, and Progression of Vulvar Intraepithelial Neoplasia

Objective Vulvar intraepithelial neoplasia (VIN) is a premalignant condition with high recurrence rates despite treatment. Vulvar intraepithelial neoplasia develops through separate etiologic pathways relative to the presence or absence of human papillomavirus (HPV) and TP53 mutations. This systematic review was conducted (1) to identify historical risk factors for the development, recurrence, and progression of VIN and (2) to critique these risk factors in the context of advances made in the stratification of VIN based on HPV or TP53 status. Materials and Methods A systematic search was performed on MEDLINE, Embase, Cochrane Database, PsychInfo, and CINAHL from inception to July 5, 2021. Three gynecologic oncologists independently evaluated the eligibility of studies based on predetermined inclusion and exclusion criteria, abstracted data, and then analyzed the relevant data. Results A total of 1,969 studies (involving 6,983 patients) were identified. Twenty-nine studies met inclusion criteria. The quality of evidence was low; primarily level 2b (Oxford Centre for Evidence-Based Medicine). Risk factors associated with the development of VIN include: smoking and coexisting vulvar dermatoses. Risk factors associated with recurrence include: smoking, multifocal disease, and positive surgical margins. Recent studies identified the presence of differentiated VIN/TP53 mutation as the most significant risk factor for both VIN recurrence and malignant progression. Conclusions The current body of evidence consists primarily of small retrospective observational studies. Well-designed retrospective case-control series and/or prospective observational studies are urgently needed. Ideally, future studies will collect standardized data regarding associated risk factors and stratify women with VIN based on HPV and TP53 status.

Differentiated Exophytic Vulvar Intraepithelial Lesions: Case Reports and Review of Literature

Objectives The aims of this article were to describe 2 patients with a pathological diagnosis of differentiated exophytic vulvar intraepithelial lesion and to summarize the literature regarding this relatively new diagnosis. Materials and Methods The existing literature was searched on December 1, 2021, using the MEDLINE database (1966–2021), and all combinations of the following search terms were used: “differentiated exophytic vulvar intraepithelial lesion” and “differentiated vulvar intraepithelial neoplasia.” Results Patients were postmenopausal and reported persistent vulvar itch associated with white hypertrophic plaques. Initial biopsies did not identify differentiated exophytic vulvar intraepithelial lesion. Invasive squamous cell carcinoma was found in both cases after surgical excision. Conclusions Differentiated vulvar intraepithelial lesions and invasive squamous cell carcinoma should be considered in the differential diagnosis of vulvar itch associated with hypertrophic plaques in postmenopausal women. Excision of suspicious plaques is recommended for definitive diagnosis.

Risk of Development of Vulvar Cancer in Women With Lichen Sclerosus or Lichen Planus: A Systematic Review

Objective Vulvar lichen sclerosus (VLS) and possibly vulvar lichen planus (VLP) are associated with an increased vulvar cancer (VC) risk. We analyzed the risk of VC and its precursors after a diagnosis of VLS or VLP. Materials and Methods A search was performed to identify articles describing the development of vulvar neoplasia in women with VLS or VLP. This systematic review was registered with the PROSPERO database. Results Fourteen studies on VLS included 14,030 women without a history of vulvar neoplasia. Vulvar cancer, differentiated vulvar intraepithelial neoplasia (dVIN), and vulvar high-grade squamous intraepithelial lesion occurred in 2.2% (314/14,030), 1.2% (50/4,175), and 0.4% (2/460), respectively. Considering women with previous or current VC, the rate was 4.0% (580/14,372). In one study, dVIN preceded VC in 52.0% of the cases. Progression of dVIN to VC was 18.1% (2/11). The risk was significantly higher in the first 1–3 years after a biopsy of VLS and with advancing age; it significantly decreased with ultrapotent topical steroid use. For the 14,268 women with VLP (8 studies), the rates of VC, dVIN, and vulvar high-grade squamous intraepithelial lesion were 0.3% (38/14,268), 2.5% (17/689), and 1.4% (10/711), respectively. Conclusions Vulvar lichen sclerosus is associated with an increased risk of VC, especially in the presence of dVIN and with advancing age. Ultrapotent topical steroids seem to reduce this risk. An increased risk of developing VC has been suggested for VLP. Hence, treatment and regular life-long follow-up should be offered to women with VLS or VLP.

Metastatic Neoplasms to the Vulva—A Review

Introduction Metastatic neoplasms to the vulva are rare and can pose a diagnostic dilemma. As identification of the primary site can influence patient treatment and prognosis, correct diagnosis is important. Methods PubMed was searched for applicable publications using the terms vulva, vulvar neoplasms, metastasis, and vulvar metastasis. Results Most neoplasms metastatic to the vulva originate from other genital sources; however, extragenital primary neoplasms can also metastasize to the vulva. Vulvar metastases often occur in the setting of widespread disease. Conclusions It is important to consider biopsy for appropriate histologic and immunohistochemical studies, as well as consider patient history to establish the primary site of metastatic lesions to the vulva, allowing optimal therapy.

Nonsquamous Lesions of the Vulvar Skin and Subcutaneous Tissue: A Review (Part 2)

Objective The aim of this second article was to complete part 1 review of nonsquamous lesions of the vulvar skin and subcutaneous tissue (Journal of Lower Genital Tract Disease, 2021), clinically and pathologically, based on the fifth edition of the World Health Organization tumor classification. Materials and Methods A database search of PubMed and Google Scholar was performed between 1970 and 2021, using the search terms “vulva,” “lower genital tract,” and “non-squamous lesions.” The search was limited to “human gynecological pathology.” Full article texts were reviewed, and reference lists were screened for additional articles. We excluded abstracts and articles written in the non-English language. Results An initial list of 400 articles was identified. Thirty-seven articles discussed clinicopathological features of nonsquamous lesions of the vulvar skin and subcutaneous tissue. Conclusions Clinicopathological features of nonsquamous lesions of the vulvar skin and subcutaneous tissue as categorized by the updated World Health Organization classification are presented.

Vulvar Vascular Malformations in Children and Adolescents—A Report of a Rare Entity and Review of the Literature

Vulvar High-Grade Squamous Intraepithelial Lesions and Cancer as a Risk Factor for Anal Cancer: A Review

Objectives Anal squamous cell carcinoma (ASCC) has a higher incidence described in certain groups, namely, in women with vulvar high-grade squamous intraepithelial lesions (vHSILs) and/or human papillomavirus squamous cell carcinoma (VSCC). This review describes terminology, vHSIL, and VSCC in their association with ASCC and the published recommendations for early detection of this cancer in these women. Materials and Methods A narrative review was conducted by the authors on vHSIL and VSCC as risk factors for ASCC. Results The ASCC and VSCC incidence are increasing. Women with vHSIL and/or VSCC can present with ASCC at diagnosis, being one of the highest-risk groups. Suspicious symptoms include rectal bleeding, pain, and a sensation of an anal mass. Digital anorectal examination can help detect early ASCC. Sensitivity of anal cytology in women with vHSIL and VSCC seems low, with the exception of immunosuppressed women with genital neoplasia (cervix, vagina, and vulva). There are still insufficient data on high-resolution anoscopy in women with vHSIL and/or VSCC as a screening method. Conclusions Clinicians need be aware that women with vHSIL and VSCC comprise one of the highest-risk groups for ASCC. Inquiring suggestive symptoms of ASCC and a digital anorectal examination can help in the early detection of this type of cancer.

Association Between Vulvar Squamous Intraepithelial Lesions and Psychiatric Illness

Objectives The aims of the study were to describe and to compare demographics and the prevalence of psychiatric disorders among patients with low- and high-grade vulvar squamous intraepithelial lesions. Methods A retrospective chart review was performed for patients presenting to a vulvar diseases clinic between 1996 and 2019 (N = 2,462). Intake questionnaire data were entered into a deidentified database. Results were compared between 80 patients with biopsy-confirmed high-grade squamous intraepithelial lesions (HSILs) and 48 patients with biopsy-confirmed low-grade squamous intraepithelial lesions (LSILs). Bivariate analysis was performed to compare demographics and psychiatric treatment and outcomes across HSIL and LSIL groups. Results Among 128 patients with vulvar disease, 80 (62.5%) had HSILs and 48 (37.5%) had LSILs. Patients with HSILs were significantly older (HSIL median [interquartile range] = 49.0 (39.0–61.0) vs LSIL = 36.0 [29.0–53.0], p = .006). There were no significant differences between groups across race/ethnicity, education, marital status, or self-reported household income categories. Forty percent of HSIL patients reported depression compared with 20.8% of LSIL patients (p = .03), whereas 31.3% of HSIL patients and 8.3% of LSIL patients reported anxiety (p = .002). Bipolar disorder was reported in 3.8% of HSIL patients and no LSIL patients (p = .29). There were no differences in the proportion of patients receiving psychiatric counseling, medications, or hospitalizations between groups. Conclusions Squamous intraepithelial lesions of the vulva are associated with psychiatric disorders above age-matched national averages; these disorders are more prominent in the HSIL group. Combining mental health services with ongoing disease treatment seem to be part of a comprehensive approach to caring for this patient population.