Citation
Ferreiro-Iglesias, Aida; McKay, James D.; Brenner, Nicole; Virani, Shama; Lesseur, Corina; Gaborieau, Valerie; Ness, Andy R.; Hung, Rayjean J.; Liu, Geoffrey; & Diergaarde, Brenda, et al. (2021). Germline Determinants of Humoral Immune Response to HPV-16 Protect against Oropharyngeal Cancer. Nature Communications, 12(1), 5945. PMCID: PMC8511029Abstract
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.URL
http://dx.doi.org/10.1038/s41467-021-26151-9Reference Type
Journal ArticleYear Published
2021Journal Title
Nature CommunicationsAuthor(s)
Ferreiro-Iglesias, AidaMcKay, James D.
Brenner, Nicole
Virani, Shama
Lesseur, Corina
Gaborieau, Valerie
Ness, Andy R.
Hung, Rayjean J.
Liu, Geoffrey
Diergaarde, Brenda
Olshan, Andrew F.
Hayes, Neil
Weissler, Mark Christian
Schroeder, Lea
Bender, Noemi
Pawlita, Michael
Thomas, Steve
Pring, Miranda
Dudding, Tom
Kanterewicz, Beatriz
Ferris, Robert L.
Thomas, Sera
Brhane, Yonathan
Díez-Obrero, Virginia
Milojevic, Maja
Smith-Byrne, Karl
Mariosa, Daniela
Johansson, Mattias
Herrero, Rolando
Boccia, Stefania
Cadoni, Gabriella
Lacko, Martin
Holcátová, Ivana
Ahrens, Wolfgang
Lagiou, Pagona
Lagiou, Areti
Polesel, Jerry
Simonato, Lorenzo
Merletti, Franco
Healy, Claire M.
Hansen, Bo T.
Nygård, Mari
Conway, David I.
Wright, Sylvia
Macfarlane, Tatiana V.
Robinson, Max
Alemany, Laia
Agudo, Antonio
Znaor, Ariana
Amos, Christopher I.
Waterboer, Tim
Brennan, Paul