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Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.

ABSTRACT: Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.

SUBMITTER: Ferreiro-Iglesias A

PROVIDER: S-EPMC8511029 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.

Ferreiro-Iglesias Aida A McKay James D JD Brenner Nicole N Virani Shama S Lesseur Corina C Gaborieau Valerie V Ness Andy R AR Hung Rayjean J RJ Liu Geoffrey G Diergaarde Brenda B Olshan Andrew F AF Hayes Neil N Weissler Mark C MC Schroeder Lea L Bender Noemi N Pawlita Michael M Thomas Steve S Pring Miranda M Dudding Tom T Kanterewicz Beatriz B Ferris Robert R Thomas Sera S Brhane Yonathan Y Díez-Obrero Virginia V Milojevic Maja M Smith-Byrne Karl K Mariosa Daniela D Johansson Mattias J MJ Herrero Rolando R Boccia Stefania S Cadoni Gabriella G Lacko Martin M Holcátová Ivana I Ahrens Wolfgang W Lagiou Pagona P Lagiou Areti A Polesel Jerry J Simonato Lorenzo L Merletti Franco F Healy Claire M CM Hansen Bo T BT Nygård Mari M Conway David I DI Wright Sylvia S Macfarlane Tatiana V TV Robinson Max M Alemany Laia L Agudo Antonio A Znaor Ariana A Amos Christopher I CI Waterboer Tim T Brennan Paul P

Nature communications 20211012 1

Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+ ...[more]

PMID: 34642315

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Project description:IntroductionHuman papillomavirus (HPV) is the primary cause of cervical and other anogenital cancers and is also associated with head and neck cancers. Incidence of HPV-related oropharyngeal squamous cell cancers (OPSCCs) is increasing, and HPV-related OPSCCs have surpassed cervical cancer as the most common HPV-related cancer in the USA. Given the multisite nature of HPV, there is strong interest in collecting data from both genital and oral sites, as well as associated data on social and sexual behaviours. The overarching goal of this study is to evaluate patterns of oral HPV infection incidence, clearance and persistence and their relationship to sexual behaviour history.Methods and analysisParticipants are recruited from two populations: college students at a large public university and general population from the surrounding area. At the first study visit, participants complete a detailed sexual history, health and behaviour questionnaire. Follow-up visits occur every 3-4 months over 3 years, when participants complete an abbreviated questionnaire. All participants provide a saliva sample at each visit, and eligible participants may provide a cervicovaginal self-swab. Genetic material isolated from specimens is tested for 15 high-risk and 3 low-risk HPV types. Statistical analyses will examine outcome variables including HPV prevalence, incidence, persistence and clearance. Logistic regression models will be used to estimate odds ratios and 95% confidence intervals for associations between the outcomes of interest and demographic/behavioural variables collected in the questionnaires. The longitudinal HPV infection data and detailed sexual history data collected in the questionnaires will allow us to develop individual-based network models of HPV transmission and will be used to parameterise multiscale models of HPV-related OPSC carcinogenesis.Ethics and disseminationThis study has been approved by the University of Michigan Institutional Review Board. All participants are consented in person by trained study staff. Study results will be disseminated through peer-reviewed publications.

Dataset Information

Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.

Publications

Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.

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