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Objectives: This study aims to assess the prevalence and factors associated with anal high-risk human papilloma virus (HR-HPV)., Design: A cross-sectional study conducted from 24 August 2020 to 24 November 2020., Setting: Primary care, Cotonou, Benin., Participants: 204 HIV-negative men who have sex with men initiating oral pre-exposure prophylaxis., Primary Outcome Measure: Anal HR-HPV genotypes using GeneXpert HPV assay. Fourteen HR-HPV were evaluated: HPV-16 and HPV-18/45 in 2 distinct channels and the 11 other genotypes as a pooled result (31, 33, 35, 39, 51, 52, 56, 58, 59, 66 and 68). The potential independent variables analysed included anal gonorrhoea and chlamydia infections, and sociodemographic and sexual behaviour factors. To assess the determinants of HR-HPV, univariate and multivariate Poisson regression models were performed by using SAS V.9.4., Results: Mean age±SD was 25.9±4.8 years. 131/204 men claimed insertive sex procured more pleasure. Thirty-two participants, accounting for 15.7% of the study sample, had gonorrhoea and/or chlamydia. The prevalence of any HR-HPV genotype was 36.3% (95% CI 30.0% to 43.0%). In total, 7.8% of men had HPV-16 and 7.4% had HPV-18/45. The prevalence for the pooled genotypes (31, 33, 35, 39, 51, 52, 56, 58, 59, 66 and 68) was 29.9%. Receptive anal sex during the last 6 months was strongly associated with prevalent HR-HPV infections. The adjusted proportion ratio (aPR) was 1.93 (95% CI 1.31 to 2.83). Gonorrhoea and chlamydia were also associated with the outcome of interest; p value for both infections was <0.05. The aPR comparing patients who perceived some risk of acquiring HIV to other men was 1.44 (95% CI 1.00 to 2.08)., Conclusions: In Benin, anal HR-HPV was common among HIV-negative men who have sex with men. Among this highly vulnerable population, there is a need for integrated preventive and management strategies targeting HPV and other sexually transmitted infections., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)