{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T05:48:23Z","timestamp":1782366503401,"version":"3.54.5"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We characterized HPV burden in 75 men (median age 53 years [IQR 41\u201360]) 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-\u03b3 ELISpot and peripheral blood T cells were analyzed by flow cytometry. Further, in a subgroup ano-mucosal CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells were profiled via low-input RNA sequencing to determine immune signatures associated with persistent HPV infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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 (\n                      <jats:italic>p<\/jats:italic>\n                      = 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\n                      <jats:sup>+<\/jats:sup>\n                      CD4\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells [\n                      <jats:italic>p<\/jats:italic>\n                      -value = 0.01 for CD4\n                      <jats:sup>+<\/jats:sup>\n                      and\n                      <jats:italic>p<\/jats:italic>\n                      -value = 0.04 for CD8\n                      <jats:sup>+<\/jats:sup>\n                      ]; Tcf1\n                      <jats:sup>\u2013<\/jats:sup>\n                      PD-1\n                      <jats:sup>+<\/jats:sup>\n                      TIM-3\n                      <jats:sup>+<\/jats:sup>\n                      CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells [\n                      <jats:italic>p<\/jats:italic>\n                      -value = 0.02]), and senescence (CD57\n                      <jats:sup>+<\/jats:sup>\n                      CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells,\n                      <jats:italic>p<\/jats:italic>\n                      -value = 0.02). Ano-mucosal CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells of HR HPV infected men living with HIV showed upregulation of genes associated with exhaustion (\n                      <jats:italic>CTLA4, CD101<\/jats:italic>\n                      ), activation and effector function (\n                      <jats:italic>GZMK, CTSW<\/jats:italic>\n                      ) compared to non-HR HPV infected men.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1855627","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T05:30:17Z","timestamp":1782365417000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["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"],"prefix":"10.3389","volume":"17","author":[{"given":"Veronica","family":"Ober","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Department of Medicine IV, LMU University Hospital, LMU Munich","place":["Munich, Germany"]},{"name":"German Centre for Infection Research, Partner Site Munich","place":["Munich, 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Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"D\u00e4chert","sequence":"additional","affiliation":[{"name":"Max Von Pettenkofer Institute, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Ibarra","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Department of Medicine IV, LMU University Hospital, LMU Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Seybold","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Department of Medicine IV, LMU University Hospital, LMU Munich","place":["Munich, Germany"]},{"name":"German Centre for Infection Research, Partner Site Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes R","family":"Bogner","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Department of Medicine IV, LMU University Hospital, LMU Munich","place":["Munich, Germany"]},{"name":"German Centre for Infection Research, Partner Site Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Geldmacher","sequence":"additional","affiliation":[{"name":"German Centre for Infection Research, Partner Site Munich","place":["Munich, Germany"]},{"name":"Institute of Infectious Diseases and Tropical Medicine, LMU University Hospital, LMU Munich","place":["Munich, Germany"]},{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology, Infection and Pandemic Research","place":["Munich, 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