High prevalence of anal HPV16 infection among HIV-negative men who have sex with men and transgender women using pre-exposure prophylaxis: a single-centre retrospective cross-sectional study

Background: Anal squamous cell carcinoma is a preventable digestive malignancy driven by persistent infection with high-risk human papillomavirus (HPV), particularly HPV16. Current anal cancer screening strategies primarily target HIV-positive populations and may not reflect evolving risk profiles in HIV-negative men who have sex with men (MSM) using pre-exposure prophylaxis (PrEP). Methods: We conducted a retrospective cross-sectional study in HIV-negative MSM and transgender women (TGW) using PrEP who underwent routine proctology consultations. Anal samples were collected for cytology and high-risk HPV DNA testing, and targeted biopsies were performed when lesions were identified on standard anoscopy. We estimated the prevalence of anal HPV16 infection, identified associated behavioral and clinical factors, and assessed the prevalence of cytological and histological anal abnormalities. Results: Among 458 participants with interpretable HPV testing, anal HPV16 infection was detected in 32.5%. HPV16 positivity was independently associated with chemsex practices (OR 1.76; 95%CI1.14-2.71) and a history of rectal bacterial sexually transmitted infections since PrEP initiation (OR 1.64; 95% CI, 1.10-2.47). Cytological abnormalities were observed in 22.9% of participants and were more frequent in those with HPV16 infection (31.1% vs. 19.1%; OR 1.9; 95%CI 1.18-3.05; p = 0.008). Histological assessment was available for 92 individuals; 18.6% had low-grade lesions and 1.3% had high-grade lesions. Overall, HPV-related histological lesions were present in 19.9% of participants. Conclusions: HIV-negative MSM and TGW using PrEP exhibit a high burden of anal HPV16 infection and cytological abnormalities. These findings suggest that selected high-risk PrEP users may benefit from targeted anal cancer screening strategies.