| Summary: | IntroductionHuman papillomavirus (HPV) prevalence is high among men who have sex with men (MSM), increasing the risk of anal cancer. Key risk factors include HIV co-infection and persistent HPV infection, although the underlying mechanisms remain unclear.MethodsWe characterized HPV burden in 75 men (median age 53 years [IQR 41–60]) presenting to LMU University Hospital or the medical practice prinzmed between 2022 and 2024. 64/75 defined themselves as MSM, 49 MSM were living HIV and 15 without HIV. 11/75 non-MSM were living with HIV. To identify systemic immunological correlates of HPV clearance or persistence, we performed IFN-γ ELISpot and peripheral blood T cells were analyzed by flow cytometry. Further, in a subgroup ano-mucosal CD8+ T cells were profiled via low-input RNA sequencing to determine immune signatures associated with persistent HPV infection.ResultsAnal HPV infection was highly prevalent at baseline (67/75) in this largely unvaccinated cohort (73/75), particularly among MSM (59/64), and was independent of HIV status. At baseline, simultaneous infection with multiple HPV types was detected in 50/64 MSM versus 4/11 non-MSM, and most infections persisted over 1 year. Type-specific systemic T-cell responses were detected in 3/4 individuals who cleared a given HR HPV type, compared with 0/14 with persistent HR HPV (p = 0.049). Among men living with HIV, HR HPV clearance was lower compared to men without HIV. Peripheral T cells in men living with HIV and infected with at least one HR HPV strain exhibited markers of exhaustion (TIM-3+ CD4+ and CD8+ T cells [p-value = 0.01 for CD4+ and p-value = 0.04 for CD8+]; Tcf1–PD-1+TIM-3+ CD4+ T cells [p-value = 0.02]), and senescence (CD57+ CD4+ T cells, p-value = 0.02). Ano-mucosal CD8+ T cells of HR HPV infected men living with HIV showed upregulation of genes associated with exhaustion (CTLA4, CD101), activation and effector function (GZMK, CTSW) compared to non-HR HPV infected men.DiscussionOur findings show a high anal HPV burden and low clearance among MSM, regardless of HIV status. Clearance was associated with type-specific systemic T-cell responses, while T-cell exhaustion and senescence may contribute to reduced clearance in men living with HIV.
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