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Ober, V.* ; Gruener, E.* ; Wang, D.Q.* ; Baranov, O.* ; Stirner, R.* ; Reiling, G.* ; Conca, R.* ; Dächert, C.* ; Ibarra, G.* ; Seybold, U.* ; Bogner, J.* ; Geldmacher, C.* ; Held, K. ; Roider, J.*

Local and systemic immune correlates of anal high-risk HPV infection and clearance in men living with HIV and men at high risk for HIV.

Front. Microbiol. 17, DOI: 10.3389/fmicb.2026.1855627 (2026)

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Introduction: Human 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.Methods: We 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.Results: Anal 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.Discussion: Our 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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Publication type Article: Journal article

Document type Scientific Article

Keywords Men Who Have Sex With Men ; Immune System ; Cohort ; Clearance ; Cd8 ; Human Immunodeficiency Virus (hiv) ; Elispot ; Hpv Infection

ISSN (print) / ISBN 1664-302X

e-ISSN 1664-302X

Journal Frontiers in Microbiology

Quellenangaben Volume: 17

Publisher Frontiers

Reviewing status Peer reviewed

Institute(s) Research Unit Global Health (UGH)