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

Author

Listed:
  • 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
    Icahn School of Medicine at Mount Sinai)

  • 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
    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
    UPMC Hillman Cancer Center)

  • 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
    Fondazione Policlinico Universitario A.Gemelli IRCCS)

  • Gabriella Cadoni

    (Institute of Clinical Otorhinolaryngology, Università Cattolica del Sacro Cuore
    Istituto di Clinica Otorinolaringoiatrica, Fondazione Policlinico Universitario A.Gemelli IRCCS)

  • 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
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública-CIBERESP)

  • 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)

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.

Suggested Citation

  • 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 & Ne, 2021. "Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26151-9
    DOI: 10.1038/s41467-021-26151-9
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    References listed on IDEAS

    as
    1. Ho Lam Chan & Felipe Beckedorff & Yusheng Zhang & Jenaro Garcia-Huidobro & Hua Jiang & Antonio Colaprico & Daniel Bilbao & Maria E. Figueroa & John LaCava & Ramin Shiekhattar & Lluis Morey, 2018. "Polycomb complexes associate with enhancers and promote oncogenic transcriptional programs in cancer through multiple mechanisms," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
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    Cited by:

    1. Abhinav Thakral & John JW. Lee & Tianzhichao Hou & Katrina Hueniken & Tom Dudding & Mark Gormley & Shama Virani & Andrew Olshan & Brenda Diergaarde & Andrew R. Ness & Tim Waterboer & Karl Smith-Byrne , 2024. "Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study," Nature Communications, Nature, vol. 15(1), pages 1-9, December.

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