Prevalence of anal dysplasia and HPV genotypes in gynecology patients: The ANGY cross-sectional prospective clinical study protocol
Authors: Pache Basile , Balaya Vincent , Mathis Jérôme , Hübner Martin , Sahli Roland , Cavassini Mathias , Sempoux Christine , Mathevet Patrice , Jacot-Guillarmod Martine 
Published: October 2022

Background
Human Papillomaviruses (HPV) are highly prevalent in the sexually active populations, with a significant burden in terms of health and psychological cost in all class ages. High-risk (HR) HPV genotypes are associated with anogenital dysplasia and cancers, and anal HPV-induced cancer is increasingly observed in women. The interactions of HPV genotype’s between the anus and the cervix, and the subsequent occurrence of dysplasia remains unclear. This clinical study set out to test the hypothesis that risk factors for anal HR-HPV and dysplasia may differ in women with or without cervical dysplasia or in HIV-positive women.

Methods
Cervical and anal HPV genotypes and cytology testing will be performed prospectively in a cohort of women recruited in a tertiary university hospital in Switzerland. Women will be allocated to three groups: 1) normal previous cervical smear; 2) high-grade cervical dysplasia (H-SIL) at previous cervical smear; 3) HIV+, independently of previous cervical smear result. General inclusion criteria comprised the followings: Female—Age > = 18 years; Satisfactory understanding of French; No objection to HIV testing. Specific inclusion criteria are: Group 1, no past or current gynecological dysplasia and HIV negative; Group 2, Gynecological dysplasia (H-SIL) or carcinoma in situ demonstrated by histology (vulvar, vaginal or cervical) and HIV negative; Group 3: HIV-positive (regardless of viremia or CD4 count) with or without gynecological dysplasia. General exclusion criteria are: Pregnancy; History of anal dysplasia/cancer; Status after pelvic radiotherapy; Absence of anus and anal canal. Estimated prevalences of anal dysplasia are: in group 1, 1% (0–2%); in group 2, 15% (5–27%), and in group 3, 30% (19–45%). With a 10% margin error, a sample size of 120 women per group is required to reach 90% power for detecting statistical significance (unilateral α error of 5%).

Discussion
The primary endpoint is the prevalence of anal and cervical dysplasia, and description of the respective HPV genotypes in each group. The results of this study could improve the standard of screening of cervical and anal dysplasia in women through evidence of concomitant presence of HPV’s and/or dysplasia in anus or cervix to support vaccination for instance. Beginning of recruitment started in September 2016. Results should be presented in end of 2022. Preliminary analysis for first 100 patients reveals that the mean age of the population is 39.6 (± 10.9) years with mean age of first sexual intercourse of 18.5 (± 3.9) years. In this cohort, 12% are vaccinated and 38% having had anal intercourse. Overall, 43% of the studied population had cervical HR-HPV in the studied population, and 53% had normal cytology. Anal LR HPV and HR HP were found in 27.6% and 38.4% of all patients respectively. Eighty percent had normal anal cytology. Groups 1,2 and 3 had a significant difference in terms of age, gestity, parity, age of first sexual intercourse, systematic use of condom, number of cervical LR HPV and HR HPV and abnormal cervical cytologies.

Trial registration
The study was approved by the institutional review board—CER-VD#2015–00200—on the 29th of June 2016 and is registered on the Swiss National Clinical Trials Portal (SNCTP), SNCTP000002567, Registered 29 June 2016, https://www.kofam.ch/en/snctp-portal/study/40742/