Depletion of Human Papilloma Virus E6- and E7-Oncoprotein-Specific T-Cell Responses in Women Living With HIV

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dc.contributor.authorMbuya, Wilbert
dc.contributor.authorMcharo, Ruby
dc.contributor.authorMhizde, Jacklina
dc.contributor.authorMnkai, Jonathan
dc.contributor.authorMahenge, Anifrid
dc.contributor.authorMwakatima, Maria
dc.contributor.authorMwalongo, Wolfram
dc.contributor.authorHoelscher, Michael
dc.contributor.authorSaathoff, Elmar
dc.contributor.authorRwegoshora, France
dc.contributor.authorTorres, Liset
dc.contributor.authorKroidl, Arne
dc.contributor.authorGeldmacher, Christof
dc.contributor.authorHeld, Kathrin
dc.contributor.authorChachage, Mkunde
dc.contributor.authorSembo, Margareth
dc.contributor.authorHaule, Antelmo
dc.contributor.authorMaboko, Leonard
dc.contributor.authorGeisenberger, Otto
dc.contributor.authorAgrea, Peter
dc.contributor.authorKoup, Richard A.
dc.date.accessioned2022-11-23T12:34:08Z
dc.date.available2022-11-23T12:34:08Z
dc.date.issued2021-10-25
dc.description.abstractBackground: Cervical cancer - caused by persistent High Risk Human Papilloma Virus (HR HPV) infections - is the second most common cancer affecting women globally. HIV infection increases the risk for HPV persistence, associated disease progression and malignant cell transformation. We therefore hypothesized that this risk increase is directly linked to HIV infection associated dysfunction or depletion of HPV-oncoprotein-specific T-cell responses. Methods: The 2H study specifically included HIV+ and HIV- women with and without cervical lesions and cancer to analyze HPV oncogene-specific T cell responses in relation to HPV infection, cervical lesion status and HIV status. Oncoprotein E6 and E7 specific T-cell responses were quantified for the most relevant types HPV16, 18 and 45 and control antigens (CMV-pp65) and M.tb-PPD in 373 women, using fresh peripheral blood mononuclear cells in an IFN-γ release ELISpot assay. Results: Overall, systemic E6- and E7-oncoprotein-specific T-cell responses were infrequent and of low magnitude, when compared to CMV-pp65 and M.tb-PPD (p < 0.001 for all HR HPV types). Within HIV negative women infected with either HPV16, 18 or 45, HPV16 infected women had lowest frequency of autologous-type-E6/E7-specific T-cell responses (33%, 16/49), as compared to HPV18 (46% (6/13), p = 0.516) and HPV45 (69% (9/13), p = 0.026) infected women. Prevalent HPV18 and 45, but not HPV16 infections were linked to detectable oncoprotein-specific T-cell responses, and for these infections, HIV infection significantly diminished T-cell responses targeting the autologous infecting genotype. Within women living with HIV, low CD4 T-cell counts, detectable HIV viremia as well as cancerous and precancerous lesions were significantly associated with depletion of HPV oncoprotein-specific T-cell responses. Discussion: Depletion of HPV-oncoprotein-specific T-cell responses likely contributes to the increased risk for HR HPV persistence and associated cancerogenesis in women living with HIV. The low inherent immunogenicity of HPV16 oncoproteins may contribute to the exceptional potential for cancerogenesis associated with HPV16 infections.en_US
dc.description.sponsorshipDFG African cooperation projects in Infectiology (grant 2128/2-1).en_US
dc.identifier.citationMbuya Wilbert, Held Kathrin, Mcharo Ruby D., Haule Antelmo, Mhizde Jacklina, Mnkai Jonathan, Mahenge Anifrid, Mwakatima Maria, Sembo Margareth, Mwalongo Wolfram, Agrea Peter, Hoelscher Michael, Maboko Leonard, Saathoff Elmar, Geisenberger Otto, Rwegoshora France, Torres Liset, Koup Richard A., Kroidl Arne, Chachage Mkunde, Geldmacher Christof (2021) Depletion of Human Papilloma Virus E6- and E7-Oncoprotein-Specific T-Cell Responses in Women Living With HIV. Frontiers in Immunology:12. https://www.frontiersin.org/articles/10.3389/fimmu.2021.742861.10.3389/fimmu.2021.742861en_US
dc.identifier.issn1664-3224
dc.identifier.issn1664-3224
dc.identifier.urihttp://hdl.handle.net/20.500.11810/5905
dc.language.isoenen_US
dc.publisherFrontiers Media S.A.en_US
dc.subjectHPV, HIV, T-cell response, oncoprotein, cervical canceren_US
dc.titleDepletion of Human Papilloma Virus E6- and E7-Oncoprotein-Specific T-Cell Responses in Women Living With HIVen_US
dc.title.alternativeDepletion and activation of mucosal CD4 T cellsen_US
dc.title.alternativeHR HPV-Oncoprotein-Specific T-Cell Responsesen_US
dc.typeJournal Article, Peer Revieweden_US
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