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

被引：0

作者：

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

机构：

[1] Section of Genetics,Department of Environmental Medicine and Public Health

[2] Genetic Epidemiology Group,Bristol Dental School

[3] International Agency for Research on Cancer,Department of Human Genetics, Graduate School of Public Health

[4] World Health Organization,Department of Epidemiology

[5] Section of Genetics,Division of Medical Oncology and Center for Cancer Research

[6] Genetic Cancer Susceptibility Group,Department of Otolaryngology/Head and Neck Surgery

[7] International Agency for Research on Cancer,Section of Hygiene, University Department of Life Sciences and Public Health

[8] World Health Organization,Department of Woman and Child Health and Public Health

[9] Infections and Cancer Epidemiology, Public Health Area

[10] German Cancer Research Center (DKFZ),Department of Head and Neck Surgery

[11] Icahn School of Medicine at Mount Sinai,Department of Otorhinolaryngology, Head and Neck Surgery

[12] National Institute for Health Research (NIHR) Bristol Biomedical Research Centre,School of Medicine

[13] University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol,School of Public Health

[14] University of Bristol,Department of Research

[15] Prosserman Centre for Population Health Research,School of Medicine, Dentistry, and Nursing

[16] Lunenfeld-Tanenbaum Research Institute,undefined

[17] Sinai Health System,undefined

[18] Lunenfeld-Tanenbaum Research Institute of Sinai Health System,undefined

[19] University of Toronto,undefined

[20] University of Pittsburgh,undefined

[21] UPMC Hillman Cancer Center,undefined

[22] Gillings School of Global Public Health,undefined

[23] University of North Carolina at Chapel Hill,undefined

[24] University of Tennessee Health Science Center,undefined

[25] University of North Carolina at Chapel Hill,undefined

[26] Chapel Hill,undefined

[27] Oncology Data Analytics Program,undefined

[28] Catalan Institute of Oncology (ICO),undefined

[29] Section of Early Detection and Prevention,undefined

[30] Prevention and Implementation Group,undefined

[31] International Agency for Research on Cancer,undefined

[32] World Health Organization,undefined

[33] Università Cattolica del Sacro Cuore,undefined

[34] Fondazione Policlinico Universitario A.Gemelli IRCCS,undefined

[35] Institute of Clinical Otorhinolaryngology,undefined

[36] Università Cattolica del Sacro Cuore,undefined

[37] Istituto di Clinica Otorinolaringoiatrica,undefined

[38] Fondazione Policlinico Universitario A.Gemelli IRCCS,undefined

[39] Maastricht University Medical Center,undefined

[40] Institute of Hygiene and Epidemiology,undefined

[41] University Bremen,undefined

[42] National and Kapodistrian University of Athens,undefined

[43] University of West Attica,undefined

[44] National Cancer Institute,undefined

[45] IRCCS,undefined

[46] University of Padova,undefined

[47] CeRMS and University of Turin,undefined

[48] Trinity College School of Dental Science,undefined

[49] Cancer Registry of Norway,undefined

[50] Cancer Registry of Norway,undefined

来源：

Nature Communications | / 12卷

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摘要：

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.

引用

共 50 条

[1] Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer
Ferreiro-Iglesias, Aida
McKay, 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
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Schroeder, Lea
Bender, Noemi
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