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

by Pawlita, Michael , Bender, Noemi , Weissler, Mark C. , Herrero, Rolando , Ferris, Robert , Ferreiro-Iglesias, Aida , Brenner, Nicole , Lacko, Martin , Agudo, Antonio , Lagiou, Pagona , Macfarlane, Tatiana V. , Kanterewicz, Beatriz , Healy, Claire M. , Díez-Obrero, Virginia , Gaborieau, Valerie , Lesseur, Corina , Dudding, Tom , Johansson, Mattias J. , Simonato, Lorenzo , Conway, David I. , Wright, Sylvia , Milojevic, Maja , Virani, Shama , McKay, James D. , Pring, Miranda , Liu, Geoffrey , Nygård, Mari , Robinson, Max , Thomas, Steve , Ness, Andy R. , Alemany, Laia , Waterboer, Tim , Thomas, Sera , Smith-Byrne, Karl , Boccia, Stefania , Lagiou, Areti , Diergaarde, Brenda , Merletti, Franco , Hayes, Neil , Hung, Rayjean J. , Ahrens, Wolfgang , Amos, Christopher I. , Cadoni, Gabriella , Mariosa, Daniela , Schroeder, Lea , Brennan, Paul , Holcátová, Ivana , Brhane, Yonathan , Znaor, Ariana , Hansen, Bo T. , Olshan, Andrew F. , Polesel, Jerry

in 45/43 / 631/208/205/2138 / 631/67/1536/1665 / 631/67/1858 / 631/67/580 / 692/4028/67/68 / Aged / Antibodies / Antibodies, Viral - biosynthesis / Antigenic determinants / Cancer / Capsid protein / Capsid Proteins - genetics / Capsid Proteins - immunology / Case-Control Studies / Female / Gene Expression / Genetic Predisposition to Disease / Genome-Wide Association Study / Genomes / Haplotypes / Head & neck cancer / HLA Antigens - classification / HLA Antigens - genetics / HLA Antigens - immunology / Human papillomavirus / Human papillomavirus 16 - immunology / Human papillomavirus 16 - pathogenicity / Humanities and Social Sciences / Humans / Immune response / Immune response (humoral) / Immune system / Immunity, Humoral / Loci / Male / Meta-Analysis as Topic / Middle Aged / Mouth Neoplasms - genetics / Mouth Neoplasms - immunology / Mouth Neoplasms - pathology / Mouth Neoplasms - virology / multidisciplinary / Oncogene Proteins, Viral - genetics / Oncogene Proteins, Viral - immunology / Oral cancer / Oral carcinoma / Oral cavity / Oropharyngeal cancer / Oropharyngeal Neoplasms - genetics / Oropharyngeal Neoplasms - immunology / Oropharyngeal Neoplasms - pathology / Oropharyngeal Neoplasms - virology / Papillomavirus Infections - genetics / Papillomavirus Infections - immunology / Papillomavirus Infections - pathology / Papillomavirus Infections - virology / Proteins / Quantitative Trait Loci / Repressor Proteins - genetics / Repressor Proteins - immunology / Risk Factors / Science / Science (multidisciplinary) / Serology / Smoking - physiopathology / Throat cancer

2021

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

2021

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2021

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Journal Article

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

Pawlita, Michael,

Bender, Noemi,

Weissler, Mark C.,

Herrero, Rolando,

Ferris, Robert,

Ferreiro-Iglesias, Aida,

Brenner, Nicole,

Lacko, Martin,

Agudo, Antonio,

Lagiou, Pagona,

Macfarlane, Tatiana V.,

Kanterewicz, Beatriz,

Healy, Claire M.,

Díez-Obrero, Virginia,

Gaborieau, Valerie,

Lesseur, Corina,

Dudding, Tom,

Johansson, Mattias J.,

Simonato, Lorenzo,

Conway, David I.,

Wright, Sylvia,

Milojevic, Maja,

Virani, Shama,

McKay, James D.,

Pring, Miranda,

Liu, Geoffrey,

Nygård, Mari,

Robinson, Max,

Thomas, Steve,

Ness, Andy R.,

Alemany, Laia,

Waterboer, Tim,

Thomas, Sera,

Smith-Byrne, Karl,

Boccia, Stefania,

Lagiou, Areti,

Diergaarde, Brenda,

Merletti, Franco,

Hayes, Neil,

Hung, Rayjean J.,

Ahrens, Wolfgang,

Amos, Christopher I.,

Cadoni, Gabriella,

Mariosa, Daniela,

Schroeder, Lea,

Brennan, Paul,

Holcátová, Ivana,

Brhane, Yonathan,

Znaor, Ariana,

Hansen, Bo T.,

Olshan, Andrew F.,

Polesel, Jerry

2021

Overview

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. Genetic susceptibility loci for oropharyngeal cancer have been reported but these studies have not always examined human papillomavirus (HPV) status. Here, the authors perform genome-wide analysis taking into account HPV16 serology status and report two independent loci in the HLA region, suggesting the protective role of HLA variants against HPV infection.

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Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

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