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; Paul Brennan

doi:10.1038/s41467-021-26151-9

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, Paul Brennan

International Agency for Research on Cancer
German Cancer Research Center
University Hospitals Bristol and Weston NHS Foundation Trust
Sinai Health System
University of Toronto
University of Pittsburgh
University of North Carolina at Chapel Hill
University of Tennessee Health Science Center
University of Bristol
Institute Catala Oncologia
Maastricht University
Institute of Hygiene and Epidemiology
University of Bremen
University of West Attica
IRCCS Centro di Riferimento Oncologico - Aviano PN
University of Padua
University of Turin
Trinity College Dublin
Cancer Registry of Norway Institute of Population-Based Cancer Research
University of Glasgow
Queen Elizabeth University Hospital
University of Aberdeen
Newcastle University
Baylor College of Medicine

Risultato della ricerca: Contributo in rivista › Articolo

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.

Lingua originale	Inglese
pagine (da-a)	1-11
Numero di pagine	11
Rivista	Nature Communications
Volume	12
DOI	https://doi.org/10.1038/s41467-021-26151-9
Stato di pubblicazione	Pubblicato - 2021

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Keywords

HPV16
oropharyngeal cancer

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10.1038/s41467-021-26151-9

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Ferreiro-Iglesias, A., Mckay, J. D., Brenner, N., Virani, S., Lesseur, C., Gaborieau, V., Ness, A. R., Hung, R. J., Liu, G., Diergaarde, B., Olshan, A. F., Hayes, N., Weissler, M. C., Schroeder, L., Bender, N., Pawlita, M., Thomas, S., Pring, M., Dudding, T., ... Brennan, P. (2021). Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer. Nature Communications, 12, 1-11. https://doi.org/10.1038/s41467-021-26151-9

@article{63f385c958664169a86d694b0d44cc08,

title = "Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer",

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.",

keywords = "HPV16, oropharyngeal cancer, HPV16, oropharyngeal cancer",

author = "Aida Ferreiro-Iglesias and Mckay, \{James D.\} and Nicole Brenner and Shama Virani and Corina Lesseur and Valerie Gaborieau and Ness, \{Andy R.\} and Hung, \{Rayjean J.\} and Geoffrey Liu and Brenda Diergaarde and Olshan, \{Andrew F.\} and Neil Hayes and Weissler, \{Mark C.\} and Lea Schroeder and Noemi Bender and Michael Pawlita and Steve Thomas and Miranda Pring and Tom Dudding and Beatriz Kanterewicz and Robert Ferris and Sera Thomas and Yonathan Brhane and Virginia D{\'i}ez-Obrero and Maja Milojevic and Karl Smith-Byrne and Daniela Mariosa and Johansson, \{Mattias J.\} and Rolando Herrero and Stefania Boccia and Gabriella Cadoni and Martin Lacko and Ivana Holc{\'a}tov{\'a} and Wolfgang Ahrens and Pagona Lagiou and Areti Lagiou and Jerry Polesel and Lorenzo Simonato and Franco Merletti and Healy, \{Claire M.\} and Hansen, \{Bo T.\} and Mari Nyg{\aa}rd and Conway, \{David I.\} and Sylvia Wright and Macfarlane, \{Tatiana V.\} and Max Robinson and Laia Alemany and Antonio Agudo and Ariana Znaor and Amos, \{Christopher I.\} and Tim Waterboer and Paul Brennan",

year = "2021",

doi = "10.1038/s41467-021-26151-9",

language = "English",

volume = "12",

pages = "1--11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

}

Ferreiro-Iglesias, A, Mckay, JD, Brenner, N, Virani, S, Lesseur, C, Gaborieau, V, Ness, AR, Hung, RJ, Liu, G, Diergaarde, B, Olshan, AF, Hayes, N, Weissler, MC, Schroeder, L, Bender, N, Pawlita, M, Thomas, S, Pring, M, Dudding, T, Kanterewicz, B, Ferris, R, Thomas, S, Brhane, Y, Díez-Obrero, V, Milojevic, M, Smith-Byrne, K, Mariosa, D, Johansson, MJ, Herrero, R, Boccia, S , Cadoni, G, Lacko, M, Holcátová, I, Ahrens, W, Lagiou, P, Lagiou, A, Polesel, J, Simonato, L, Merletti, F, Healy, CM, Hansen, BT, Nygård, M, Conway, DI, Wright, S, Macfarlane, TV, Robinson, M, Alemany, L, Agudo, A, Znaor, A, Amos, CI, Waterboer, T & Brennan, P 2021, 'Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer', Nature Communications, vol. 12, pagg. 1-11. https://doi.org/10.1038/s41467-021-26151-9

TY - JOUR

T1 - Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer

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

PY - 2021

Y1 - 2021

N2 - 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.

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.

KW - HPV16

KW - oropharyngeal cancer

KW - HPV16

KW - oropharyngeal cancer

UR - http://hdl.handle.net/10807/187165

U2 - 10.1038/s41467-021-26151-9

DO - 10.1038/s41467-021-26151-9

M3 - Article

SN - 2041-1723

VL - 12

SP - 1

EP - 11

JO - Nature Communications

JF - Nature Communications

ER -

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

Abstract

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Keywords

Accesso al documento

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