Anal Cancer Precursors Research Articles

S342 Interoperable Artificial Intelligence for High-Resolution Anoscopy: A Transatlantic Collaborative Study in Anal Cancer Precursor Detection and Differentiation

S342 Interoperable Artificial Intelligence for High-Resolution Anoscopy: A Transatlantic Collaborative Study in Anal Cancer Precursor Detection and Differentiation

Gastroenterology healthcare in LGBTQ+ individuals.

Lesbian, gay, bisexual, transgender, queer, or questioning individuals, as well as those with another diverse identity (LGBTQ+), present specific nuances in healthcare that physicians must consider in clinical practice. Particularly, gastroenterologists are nowadays facing different issues in several fields regarding LGBTQ+ healthcare, such as endoscopy, inflammatory bowel disease, hepatology, and proctology. In this study, the authors provide a practice-oriented and up-to-date review reinforcing the importance of some of the most prevalent pathologies associated with sexuality that gastroenterologists may encounter in their clinical practice. In terms of endoscopy, authors describe the endoscopic findings related to human papillomavirus (HPV) infection: the esophageal squamous papilloma and cell carcinoma; also highlight the importance of retroflexion maneuver during a routine colonoscopy that allows detection of anal intraepithelial neoplasia lesions that can be anal cancer precursors. Regarding inflammatory bowel disease, some considerations are made about the differential diagnosis with infectious proctitis, and the topic of the risk of anal cancer due to HPV infection, in this specific population, is also addressed. Considering hepatology, the authors review the most important issues related to hepatotropic sexually transmitted infections. The authors also make some comments regarding the possibility of drug-induced liver injury in gender-affirming hormone therapy and pre-exposure prophylaxis for HIV prevention. Finally, considering the proctology field, an up-to-date review is performed regarding anal cancer screening, HPV infection and related diseases, and infectious proctitis management.

Distinct anal microbiome is correlated with anal cancer precursors in MSM with HIV.

Anal cancer risk is elevated in MSM with HIV (MSMWH). Anal high-risk human papillomavirus (hr-HPV) infection is necessary but insufficient to develop high-grade squamous intraepithelial lesion (HSIL), the anal cancer precursor, suggesting additional factors. We sought to determine whether the microbiome of the anal canal is distinct by comparing it with the microbiome of stool. We also sought to determine whether changes in the anal microbiome are associated with HSIL among MSMWH. Cross-sectional comparison of the microbiome of the anal canal with the microbiome of stool in MSMWH and cross-sectional comparison of the anal microbiome of MSMWH with anal HSIL with the anal microbiome of MSMWH without anal HSIL. Sterile swabs were used to sample the anus of MSMWH for microbiome and HPV testing, followed by high-resolution anoscopy. Stool samples were mailed from home. 16S sequencing was used for bacterial identification. Measures of alpha diversity, beta diversity, and differential abundance analysis were used to compare samples. One hundred sixty-six anal samples and 103 matching stool samples were sequenced. Beta diversity showed clustering of stool and anal samples. Of hr-HPV-positive MSMWH, 31 had HSIL and 13 had no SIL. Comparison of the microbiome between these revealed 28 different species. The highest-fold enrichment among MSMWH/hr-HPV/HSIL included pro-inflammatory and carcinogenic Prevotella, Parasuterella, Hungatella, Sneathia, and Fusobacterium species. The anti-inflammatory Anaerostipes caccae showed the greatest reduction among MSMWH/hr-HPV/HSIL. The anal microbiome is distinct from stool. A pro-inflammatory and carcinogenic environment may be associated with anal HSIL.

Deep Learning in High-Resolution Anoscopy: Assessing the Impact of Staining and Therapeutic Manipulation on Automated Detection of Anal Cancer Precursors.

High-resolution anoscopy (HRA) is the gold standard for detecting anal squamous cell carcinoma (ASCC) precursors. Preliminary studies on the application of artificial intelligence (AI) models to this modality have revealed promising results. However, the impact of staining techniques and anal manipulation on the effectiveness of these algorithms has not been evaluated. We aimed to develop a deep learning system for automatic differentiation of high-grade squamous intraepithelial lesion vs low-grade squamous intraepithelial lesion in HRA images in different subsets of patients (nonstained, acetic acid, lugol, and after manipulation). A convolutional neural network was developed to detect and differentiate high-grade and low-grade anal squamous intraepithelial lesions based on 27,770 images from 103 HRA examinations performed in 88 patients. Subanalyses were performed to evaluate the algorithm's performance in subsets of images without staining, acetic acid, lugol, and after manipulation of the anal canal. The sensitivity, specificity, accuracy, positive and negative predictive values, and area under the curve were calculated. The convolutional neural network achieved an overall accuracy of 98.3%. The algorithm had a sensitivity and specificity of 97.4% and 99.2%, respectively. The accuracy of the algorithm for differentiating high-grade squamous intraepithelial lesion vs low-grade squamous intraepithelial lesion varied between 91.5% (postmanipulation) and 100% (lugol) for the categories at subanalysis. The area under the curve ranged between 0.95 and 1.00. The introduction of AI to HRA may provide an accurate detection and differentiation of ASCC precursors. Our algorithm showed excellent performance at different staining settings. This is extremely important because real-time AI models during HRA examinations can help guide local treatment or detect relapsing disease.

S173 Deep Learning and High-Resolution Anoscopy: Assessing the Impact of Staining and Overcoming the Impact Therapeutic Anal Manipulation in the Automated Detection and Differentiation of Anal Squamous Cell Cancer Precursors

S173 Deep Learning and High-Resolution Anoscopy: Assessing the Impact of Staining and Overcoming the Impact Therapeutic Anal Manipulation in the Automated Detection and Differentiation of Anal Squamous Cell Cancer Precursors

Diagnosis and screening for anal intraepithelial neoplasia in Belgium: position statement.

Anal cancer is an uncommon malignancy, comprising only 2.5% of all gastrointestinal malignancies and similar to cervical cancer, the human papillomavirus (HPV) is responsible for the majority of anal cancers. Over the last decades there has been an up to 3-fold increased incidence seen in specific populations at risk such as persons living with HIV (PLWH), men who have sex with men (MSM), woman diagnosed with HPV-related gynaecological precancerous lesions or cancer, solid organ transplant recipients (SOTR) and patients with autoimmune diseases. Although international practice is evolving increasingly towards active screening for and treatment of anal cancer precursors in at-risk groups, currently no organised screening program is in effect in Belgium. Currently, differerent screening options as well as treatment modalities are available. Before commencing a nationwide organised screening program, essential decisions on screening strategies need to be made, based on both scientific as well as financial and logistical facts.

Artificial intelligence and high-resolution anoscopy: automatic identification of anal squamous cell carcinoma precursors using a convolutional neural network.

High-resolution anoscopy (HRA) is the gold standard for detecting anal squamous cell cancer (ASCC) precursors. Although it is superior to other diagnostic methods, particularly cytology, the visual identification of areas suspected of having high-grade squamous intraepithelial lesions remains difficult. Convolutional neural networks (CNNs) have shown great potential for assessing endoscopic images. The aim of the present study was to develop a CNN-based system for automatic detection and differentiation of HSIL versus LSIL in HRA images. A CNN was developed based on 78 HRA exams from a total of 71 patients who underwent HRA at a single high-volume center (GH Paris Saint-Joseph, Paris, France) between January 2021 and January 2022. A total of 5026 images were included, 1517 images containing HSIL and 3509 LSIL. A training dataset comprising 90% of the total pool of images was defined for the development of the network. The performance of the CNN was evaluated using an independent testing dataset comprising the remaining 10%. The sensitivity, specificity, accuracy, positive and negative predictive values, and area under the curve (AUC) were calculated. The algorithm was optimized for the automatic detection of HSIL and its differentiation from LSIL. Our model had an overall accuracy of 90.3%. The CNN had sensitivity, specificity, positive and negative predictive values of 91.4%, 89.7%, 80.9%, and 95.6%, respectively. The area under the curve was 0.97. The CNN architecture for application to HRA accurately detected precursors of squamous anal cancer. Further development and implementation of these tools in clinical practice may significantly modify the management of these patients.

Shared Decision-Making Concerning Anal Cancer Screening in Persons With Human Immunodeficiency Virus.

Anal high-grade squamous intraepithelial lesion (aHSIL) is the immediate precursor of anal cancer. Anal cytology is a recommended screening test to identify aHSIL among people with human immunodeficiency virus (HIV; PWH). Heterogeneity of risk for invasive anal cancer among PWH suggests the value of a shared decision-making framework regarding screening. Using a longitudinal HIV cohort with a comprehensive anal cancer screening program, we estimated the adjusted probabilities of having aHSIL on the first anal cytology. We used logistic regression models with inverse probability weighting to account for differential screening in the cohort and to construct a predicted probability nomogram for aHSIL. Sensitivity analysis was performed to estimate aHSIL prevalence corrected for misclassification bias. Of 8139 PWH under care between 2007 and 2020, 4105 (49.8%) underwent at least 1 anal cytology test. First-time cytology aHSIL was present in 502 (12.2%) PWH. The adjusted probability of having aHSIL varied from 5% to 18% depending on patient characteristics. Prespecified factors in the aHSIL prediction model included nadir CD4 cell count, ethnicity, race, age, sex, gender identity, and HIV risk factors. The ability of the model to discriminate cytological aHSIL was modest, with an area under the curve of 0.63 (95% confidence interval, .60-.65). PWH are at increased risk for aHSIL and invasive anal cancer. Risk, however, varies by patient characteristics. Individual risk factor profiles predictive of aHSIL can be modeled and operationalized as nomograms to facilitate shared decision-making conversations concerning anal cancer screening.

Anal cancer: an essay on etiology, risk conditions, vulnerability, and care of carriers

Introduction: The incidence of anal cancer is influenced by individual factors and socially determined conditions of vulnerability. In Brazil, it has increased in recent decades. A probable explanation for the growing incidence is the low coverage of screening and prevention programs. Objective: The aim of this study was to reflect on risk factors, the need for early diagnosis, and care of people with anal cancer and to associate social vulnerability in the understanding of illness and care in the Unified Health System (SUS). Methods: This is a systematic literature review with consultations carried out in open electronic databases: SciELO, Digital Library of Theses and Dissertations, and CAPES Publications Portal. The descriptors used were “anal cancer,” “anal cytology,” “anal cancer precursor lesions,” “primary prevention,” “integrality in health,” and “public health policies.” Results: Ensuring access to services is a common guideline in the literature. Based on the recovered references, two axes of analysis were built: in the first, ideas to reflect on care with collective health approaches were systematized, mainly on the etiology, biological risk factors, and conditions of vulnerability for cancer development to which the subjects are exposed. In the second, ideas to propose care technologies are put forward, with evidence from similar protocols and policies, especially the “Cervical Cancer Control Program,” which deals with a pathology with cytohistological and etiological similarities, risk factors, diagnostic techniques, and skilled health professionals. Conclusion: The reviewed sources point to the possibility of incorporating, as a SUS policy, large-scale actions of prevention, screening, and early diagnosis, to qualify and expand the initiatives of promotion and care. The professional cytotechnologist can be a decisive factor in the implementation of the care policy, expanding assistance to the population and qualifying the services.

Advancing anal cancer prevention in men.

In The Lancet HIV, Feixue Wei and colleagues1 report findings from the largest pooled analysis done to date on two important surrogates of anal cancer among men: prevalent high-risk human papillomavirus (HR-HPV) anal infection, and anal high-grade squamous intraepithelial lesions (HSIL), the precursor of anal cancer. This international collaboration combined individual-level data from 29 900 men across 64 studies in the analysis. The authors focused on three main covariates: HIV status; sexuality (men who have sex with men [MSM], including those who have sex with men only or also with women, or men who have sex with women [MSW]); and age.

Xpert HPV as a Screening Tool for Anal Histologic High-Grade Squamous Intraepithelial Lesions in Women Living With HIV.

Women living with HIV (WLWH) experience high rates of anal cancer. Screening using anal cytology, high-resolution anoscopy (HRA) with biopsies, can histologically diagnose anal cancer precursors called high-grade squamous intraepithelial lesions (HSIL). The low specificity of screening using anal cytology results in HRA referral for many WLWH without HSIL. Screening using high-risk human papillomavirus (HR-HPV) may improve specificity. Two hundred seven WLWH (63% non-Hispanic black) were screened for anal histologic HSIL (hHSIL) using cytology, HRA-guided biopsies, and Xpert HPV. Xpert performance for predicting anal hHSIL was compared with that of cytology. Usng Xpert 5 HPV genotypic results and accompanying cycle thresholds, receiver operator characteristic curve and recursive partitioning analyses were used to create predictive models for hHSIL. The performance of Xpert to predict hHSIL was not different from that of cytology with a sensitivity (Sn) of 89% and specificity (Sp) of 49%. Interpretation of Xpert was modified using genotypic results and receiver operator characteristic curve analysis, which produced a screen with an Sn and Sp of 75% and 84% for hHSIL, respectively. Another reinterpretation of Xpert was created using recursive partitioning and cycle thresholds, which predicted hHSIL with an Sn and Sp of 75% and 86%, respectively. The detection of HPV-16 was highly predictive of hHSIL in all analyses. These modified screening tests would reduce HRA referral in this population by almost half compared with anal cytology. Xpert HPV is an alternative to anal cytology to screen for anal HSIL and can be optimized to reduce the number of unnecessary HRAs performed in WLWH.

State of the Science: Screening, Surveillance, and Epidemiology of HPV-Related Malignancies.

Oropharyngeal, cervical, vulvar, and anal cancers share a common risk factor of HPV infection. HPV vaccination is currently recommended at age 11 or 12 to prevent new HPV infections for all genders with catch-up vaccination recommened up to age 26. Despite the known effectiveness of HPV vaccination to prevent HPV-related cancer, there is continued low uptake in the United States; only 40% of eligible persons were vaccinated in 2018, though rates are 70% among teenagers. Current American Cancer Society cancer screening guidelines recommend cervical cancer screening, but do not have specific recommendations for screening for other HPV-related cancers. Oropharyngeal cancer precursors have yet to be identified, and there are currently no routine screening tests for oropharyngeal cancer recommended by the U.S. Preventive Services Task Force. The U.S. Preventive Services Task Force and American Cancer Society recommend cervical cancer screening for women at average risk up to age 65, and screening guidelines do not currently differ by HPV vaccination status. Primary HPV DNA testing was first approved for cervical cancer screening in 2016 and was shown to be superior for cervical cancer prevention. Vulvar and anal cancer precursors have been identified, but optimal screening remains unclear. Examination of the anal canal and perianus is best performed by trained clinicians using high-resolution anoscopy, and effectiveness of using high-resolution anoscopy to detect and treat anal high-grade squamous intraepithelial lesions to prevent cancer is actively being researched. Current multistep approaches to control HPV-related malignancies include HPV vaccination coupled with cervical cancer screening or surveillance for oropharyngeal, vulvar, and anal cancers.

High Prevalence of Anal High-Grade Squamous Intraepithelial Lesions, and Prevention Through Human Papillomavirus Vaccination, in Young Men Who Have Sex With Men Living With Human Immunodeficiency Virus

BackgroundMen who have sex with men (MSM) are at high risk for human papillomavirus (HPV)–related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied.MethodsTwo hundred and sixty MSMLWH aged 18–26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24.ResultsAmong 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type–associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18–associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events.Conclusions18–26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type–associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination.

HPV vaccination to prevent recurrence of anal intraepithelial neoplasia in HIV+ MSM.

Objective:Anal cancer precursor lesions high-grade anal intraepithelial neoplasia (HGAIN) are highly prevalent among HIV+ MSM. Treatment of HGAIN is frustrated by high recurrence rates. We investigated the efficacy of the quadrivalent human papillomavirus (qHPV) vaccine as posttreatment adjuvant in preventing HGAIN recurrence in HIV+ MSM.Design:Randomized, double-blind, placebo-controlled, multicentre trial.Setting:Three HIV outpatient clinics in Amsterdam, the Netherlands.Subjects:HIV+ MSM with CD4+ cell count more than 350 cells/μl, biopsy-proven intra-anal HGAIN successfully treated in the past year, and lesions still in remission at enrolment, as assessed by high-resolution anoscopy (HRA).Intervention:Participants were randomized to three doses of qHPV (Gardasil-4, MSD) or placebo with vaccinations at 0, 2, and 6 months. HRA was repeated at 6, 12, and 18 months.Main outcome measure:The primary outcome was cumulative, biopsy-proven HGAIN recurrence rate at 18 months, evaluated in an intention-to-treat (ITT) (received all vaccinations) and per-protocol analysis (all vaccinations and complete follow-up).Results:We randomized 126 participants of which 64 (50.8%) received qHPV and 62 (49.2%) placebo. All participants received three vaccinations, and in both groups for two participants follow-up was incomplete. We found no difference (P = 0.38) in cumulative HGAIN recurrence rates between the qHPV (44/64, 68.8%) and placebo group (38/62, 61.3%) in the ITT analysis [absolute risk reduction −7.5 (95% confidence interval (CI) −24.1 to 9.2)]. This was similar in the per-protocol analysis.Conclusion:Despite adequate serological responses to qHPV vaccination, short-term recurrence of HGAIN was not prevented. These findings do not support qHPV vaccination as a treatment adjuvant to prevent HGAIN recurrence in HIV+ MSM.

Giant Acuminated Condyloma in a HIV Positive Migrant Patient: Is There a Benefit on Giving the HPV Vaccine To the Men Who Have Sex With Men Population? Case Report and Literature Review

Anal cancer is a serious health problem in HIV-positive Men who have Sex with Men (MSM), and precursor lesions like anal intraepithelial neoplasia; are well defined. Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)- associated anal cancer precursor lesion, is frequent among human immunodeficiency virus (HIV)-positive men who have sex with men and women (MSMW). There is a paucity of data published on the progression of high-grade AIN to invasive cancer as well as on clinical and virological characteristics comparing anal margin and anal canal carcinoma. Men who are infected with HIV and MSM are at particularly high risk for persistent HPV infection and HPV-induced lesions. The treatment of high-grade squamous intraepithelial lesions (HISL) in HIV positive MSM associating the adjuvant vaccine against HPV is likely to be cost-effective, with benefits reported in the age group above 38 years. It is convenient to design large controlled studies that enroll the MSM population infected with HIV, as in our patient; to evaluate the benefits of the HPV vaccine.

HIV-Infected Patients With Anal Cancer Precursors: Clinicopathological Characteristics and Human Papillomavirus Subtype Distribution.

HIV-Infected Patients With Anal Cancer Precursors: Clinicopathological Characteristics and Human Papillomavirus Subtype Distribution.

Risk of Anal Cancer Following Benign Anal Disease and Anal Cancer Precursor Lesions: A Danish Nationwide Cohort Study.

Human papillomavirus (HPV) is associated with the majority of anal high-grade intraepithelial neoplasia (AIN) and anal cancers. Little is known about the risk of anal cancer following a diagnosis of benign anal disease and AIN. Using data from nationwide, population-based Danish registries, a cohort of 126,174 individuals with either non-neoplastic anal disease or AIN 1 to 3 during 1970 to 2016 was followed until first occasion of anal cancer. Information on HIV status was obtained from the Danish HIV Cohort Study. The absolute risk of anal cancer was estimated using the Aalen-Johansen estimator taking into account censoring at emigration and end of follow-up and competing risk at time of death. Standardized incidence ratios (SIR) for anal cancer among individuals with non-neoplastic anal disease, including inflammatory lesions, hemorrhoids, and polyps, were estimated in Poisson models. Sex-, age-, and calendar period-specific national population rates were estimated using the Danish National Pathology Registry. Anal cancer risk increased with increasing severity of lesions, reaching 4% 5 years after diagnosis of AIN3. Even among those with non-neoplastic anal lesions, particularly inflammatory lesions, anal cancer risk was significantly higher than expected from Danish national anal cancer rates (SIR = 2.8; 95% confidence intervals, 2.3-3.2). The absolute 5-year risk of anal cancer following AIN3 was considerably higher among HIV-positive (14.1%) than HIV-negative (3.2%) individuals. Anal cancer risk increases with increasing severity of lesions and is especially high among HIV-positive individuals. Vaccination against HPV is important in the prevention of both high-grade AIN and anal cancer.

Routine Screening of Anal Cytology in Persons With Human Immunodeficiency Virus and the Impact on Invasive Anal Cancer: A Prospective Cohort Study.

The efficacy of screening programs to prevent anal cancer in persons with human immunodeficiency virus 1 (HIV-1) is unclear. To examine the impact of a screening program to detect anal cancer precursors on the incidence of cases of invasive anal squamous-cell carcinoma (IASCC) in persons with HIV-1, we performed a single-center, retrospective analysis of a prospective cohort of outpatients with HIV-1 attending a reference HIV unit from January 2005 onward. All participants were invited to participate in a continued structured screening program for anal cancer prevention. We estimated the incidence of IASCC and performed a comparative analysis between subjects enrolled in the screening program (screening group) and those who declined to participate (nonscreening group). To reduce any selection bias, a propensity score analysis was applied. We included 3111 persons with HIV-1 (1596 men-who-have-sex-with-men [MSM], 888 men-who-have-sex-with-women [MSW], 627 women; mean age, 41 years), with a median follow-up of 4.7 years (14 595 patient-years of follow-up); 1691 (54%) participated in the screening program. Ten patients were diagnosed with IASCC: 2 (MSM) in the screening group and 8 (4 MSM, 2 MSW, and 2 women) in the nonscreening group. The incidence rates of IASCC were 21.9 (95% confidence interval [CI], 2.7-70.3) and 107.0 (95% CI, 46.2-202.0) per 100 000 person-years, respectively. After a propensity score adjustment, the difference was significant in favor of the screening group (hazard ratio, 0.17; 95% CI, .03-.86). The number of cases of IASCC was significantly lower in persons with HIV engaged in an anal cytology screening program. These results should be validated in a randomized clinical trial.

Screening for anal cancer precursors among patients living with HIV in the absence of national guidelines: practitioners' perspectives.

Immunocompromised populations including people living with HIV (PLWH) suffer disproportionate burden from anal cancer, a rare cancer caused by persistent infection of the anal canal with oncogenic strains of human papillomavirus. In the US, there are no nationally adopted screening guidelines for anal cancer. In the absence of such guidelines, this study explores healthcare practitioners' screening practices for early signs of anal cancer among PLWH. Between November 2017 and June 2018, the research team completed 25 interviews among a diverse sample of healthcare practitioners who provide care for PLWH. Providers expressed frustration that screening and treatment guidelines for anal cancer were scant, and they varied in their screening practices. The majority of providers screened PLWH for anal dysplasia via the anal Pap smear; few providers were trained and had the medical equipment to conduct high-resolution anoscopy-guided biopsies, a more sensitive and specific screening method. Others screened through digital ano-rectal examinations (DARE) and both visually and with a DARE. Participants discussed how providers may be over-treating their patients who have high-grade anal intraepithelial neoplasia (AIN) and the role of biomarkers to determine whether the lesion is carcinogenic. Practitioners who provide care for PLWH are proactive in screening to help prevent and control anal cancer, a rare and slow-growing disease. Continuing to regularly surveil high-risk populations, particularly PLWH previously diagnosed with high-grade lesions, is critical to prevent and control anal cancer.

Women with anal cancer precursors: Clinical characteristics and concomitant genital tract neoplasia

Women with anal cancer precursors: Clinical characteristics and concomitant genital tract neoplasia