TY  - JOUR
AU  - Ferreiro-Iglesias, Aida
AU  - McKay, James D
AU  - Brenner, Nicole
AU  - Virani, Shama
AU  - Lesseur, Corina
AU  - Gaborieau, Valerie
AU  - Ness, Andy R
AU  - Hung, Rayjean J
AU  - Liu, Geoffrey
AU  - Diergaarde, Brenda
AU  - Olshan, Andrew F
AU  - Hayes, Neil
AU  - Weissler, Mark C
AU  - Schroeder, Lea
AU  - Bender, Noemi
AU  - Pawlita, Michael
AU  - Thomas, Steve
AU  - Pring, Miranda
AU  - Dudding, Tom
AU  - Kanterewicz, Beatriz
AU  - Ferris, Robert
AU  - Thomas, Sera
AU  - Brhane, Yonathan
AU  - Díez-Obrero, Virginia
AU  - Milojevic, Maja
AU  - Smith-Byrne, Karl
AU  - Mariosa, Daniela
AU  - Johansson, Mattias J
AU  - Herrero, Rolando
AU  - Boccia, Stefania
AU  - Cadoni, Gabriella
AU  - Lacko, Martin
AU  - Holcátová, Ivana
AU  - Ahrens, Wolfgang
AU  - Lagiou, Pagona
AU  - Lagiou, Areti
AU  - Polesel, Jerry
AU  - Simonato, Lorenzo
AU  - Merletti, Franco
AU  - Healy, Claire M
AU  - Hansen, Bo T
AU  - Nygård, Mari
AU  - Conway, David I
AU  - Wright, Sylvia
AU  - Macfarlane, Tatiana V
AU  - Robinson, Max
AU  - Alemany, Laia
AU  - Agudo, Antonio
AU  - Znaor, Ariana
AU  - Amos, Christopher I
AU  - Waterboer, Tim
AU  - Brennan, Paul
TI  - Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.
JO  - Nature Communications
VL  - 12
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2021-02250
SP  - 5945
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:34642315
DO  - DOI:10.1038/s41467-021-26151-9
UR  - https://inrepo02.dkfz.de/record/177020
ER  -