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Lookup NU author(s): Dr Max RobinsonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021, The Author(s).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.
Author(s): Ferreiro-Iglesias A, McKay JD, Brenner N, Virani S, Lesseur C, Gaborieau V, Ness AR, Hung RJ, Liu G, Diergaarde B, Olshan AF, Hayes N, Weissler MC, Schroeder L, Bender N, Pawlita M, Thomas S, Pring M, Dudding T, Kanterewicz B, Ferris R, Thomas S, Brhane Y, Diez-Obrero V, Milojevic M, Smith-Byrne K, Mariosa D, Johansson MJ, Herrero R, Boccia S, Cadoni G, Lacko M, Holcatova I, Ahrens W, Lagiou P, Lagiou A, Polesel J, Simonato L, Merletti F, Healy CM, Hansen BT, Nygard M, Conway DI, Wright S, Macfarlane TV, Robinson M, Alemany L, Agudo A, Znaor A, Amos CI, Waterboer T, Brennan P
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2021
Volume: 12
Issue: 1
Print publication date: 01/12/2021
Online publication date: 12/10/2021
Acceptance date: 13/09/2021
Date deposited: 02/11/2021
ISSN (electronic): 2041-1723
Publisher: Nature Research
URL: https://doi.org/10.1038/s41467-021-26151-9
DOI: 10.1038/s41467-021-26151-9
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