Germline Determinants of Humoral Immune Response To HPV-16 Protect Against Oropharyngeal Cancer

Aida Ferreiro-Iglesias, James McKay, Nicole Brenner, Shama Virani, Corina Lesseur, Valerie Gaborieau, Andrew R Ness, Rayjean J. Hung, Geoffrey Liu, Brenda Diergaarde, Andrew Olshan, Neil Hayes, Mark C Weissler, Lea Schroeder, Noemi Bender, Michael Pawlita, Steve J Thomas, Miranda Pring, Tom Dudding, Beatriz KanterewiczRobert L. Ferris, Sera Thomas, Yonathan Brhane, Virginia Diez-Obero, Maja Milojevic, Karl Smith Byrne , Daniela Mariosa, Mattias J Johansson, Rolando Herrero, Stefania Boccia, Gabriella Cadoni, Martin Lacko, Ivana Holcátová, Wolfgang Ahrens, Pagona Lagiou, Areti Lagiou, Jerry Polesel, Lorenzo Simonato, Franco Merletti, Claire M Healy, Bo T Hansen, Mari Nygaard, David I Conway, Sylvia Wright, Tatiana Macfarlane, Max Robinson, Laia Alemany, Antonio Agudo, Ariana Znaor, Christopher Amos, Tim Waterboer, Paul Brennan*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review


Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conducted a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer(OCC)) and 5,256 controls. Four novel susceptibility loci were detected 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, revealed 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.
Original languageEnglish
JournalNature Communications
Publication statusAccepted/In press - 6 Jul 2021


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