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

Aida Ferreiro-Iglesias (), James D. McKay, Nicole Brenner, Shama Virani, Corina Lesseur, Valerie Gaborieau, Andy R. Ness, Rayjean J. Hung, Geoffrey Liu, Brenda Diergaarde, Andrew F. Olshan, Neil Hayes, Mark C. Weissler, Lea Schroeder, Noemi Bender, Michael Pawlita, Steve Thomas, Miranda Pring, Tom Dudding, Beatriz Kanterewicz, Robert Ferris, Sera Thomas, Yonathan Brhane, Virginia Díez-Obrero, 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 Nygård, David I. Conway, Sylvia Wright, Tatiana V. Macfarlane, Max Robinson, Laia Alemany, Antonio Agudo, Ariana Znaor, Christopher I. Amos, Tim Waterboer and Paul Brennan ()
Additional contact information
Aida Ferreiro-Iglesias: Section of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization
James D. McKay: Section of Genetics, Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, World Health Organization
Nicole Brenner: Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ)
Shama Virani: Section of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization
Corina Lesseur: Section of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization
Valerie Gaborieau: Section of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization
Andy R. Ness: National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol
Rayjean J. Hung: Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System
Geoffrey Liu: Lunenfeld-Tanenbaum Research Institute of Sinai Health System, University of Toronto
Brenda Diergaarde: University of Pittsburgh
Andrew F. Olshan: Gillings School of Global Public Health, University of North Carolina at Chapel Hill
Neil Hayes: University of Tennessee Health Science Center
Mark C. Weissler: University of North Carolina at Chapel Hill, Chapel Hill
Lea Schroeder: Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ)
Noemi Bender: Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ)
Michael Pawlita: Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ)
Steve Thomas: University of Bristol
Miranda Pring: University of Bristol
Tom Dudding: University of Bristol
Beatriz Kanterewicz: UPMC Hillman Cancer Center
Robert Ferris: UPMC Hillman Cancer Center
Sera Thomas: Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System
Yonathan Brhane: Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System
Virginia Díez-Obrero: Oncology Data Analytics Program, Catalan Institute of Oncology (ICO)
Maja Milojevic: Section of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization
Karl Smith-Byrne: Section of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization
Daniela Mariosa: Section of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization
Mattias J. Johansson: Section of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization
Rolando Herrero: Section of Early Detection and Prevention, Prevention and Implementation Group, International Agency for Research on Cancer, World Health Organization
Stefania Boccia: Università Cattolica del Sacro Cuore
Gabriella Cadoni: Institute of Clinical Otorhinolaryngology, Università Cattolica del Sacro Cuore
Martin Lacko: Maastricht University Medical Center
Ivana Holcátová: Institute of Hygiene and Epidemiology
Wolfgang Ahrens: University Bremen
Pagona Lagiou: National and Kapodistrian University of Athens
Areti Lagiou: University of West Attica
Jerry Polesel: National Cancer Institute, IRCCS
Lorenzo Simonato: University of Padova
Franco Merletti: CeRMS and University of Turin
Claire M. Healy: Trinity College School of Dental Science
Bo T. Hansen: Cancer Registry of Norway
Mari Nygård: Cancer Registry of Norway
David I. Conway: University of Glasgow
Sylvia Wright: Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde
Tatiana V. Macfarlane: University of Aberdeen
Max Robinson: Centre for Oral Health Research, Newcastle University
Laia Alemany: Catalan Institute of Oncology/IDIBELL
Antonio Agudo: Catalan Institute of Oncology/IDIBELL
Ariana Znaor: Cancer Surveillance Section, International Agency for Research on Cancer, World Health Organization
Christopher I. Amos: Department of Medicine, Baylor College of Medicine
Tim Waterboer: Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ)
Paul Brennan: Section of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-26151-9

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