Cargando…
Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511029/ https://www.ncbi.nlm.nih.gov/pubmed/34642315 http://dx.doi.org/10.1038/s41467-021-26151-9 |
_version_ | 1784582698729209856 |
---|---|
author | 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 Weissler, Mark C. Schroeder, Lea Bender, Noemi Pawlita, Michael Thomas, Steve Pring, Miranda Dudding, Tom Kanterewicz, Beatriz Ferris, Robert Thomas, Sera Brhane, Yonathan Díez-Obrero, Virginia Milojevic, Maja Smith-Byrne, Karl Mariosa, Daniela Johansson, Mattias J. Herrero, Rolando Boccia, Stefania Cadoni, Gabriella Lacko, Martin Holcátová, Ivana Ahrens, Wolfgang Lagiou, Pagona Lagiou, Areti Polesel, Jerry Simonato, Lorenzo Merletti, Franco Healy, Claire M. Hansen, Bo T. Nygård, Mari Conway, David I. Wright, Sylvia Macfarlane, Tatiana V. Robinson, Max Alemany, Laia Agudo, Antonio Znaor, Ariana Amos, Christopher I. Waterboer, Tim Brennan, Paul |
author_facet | 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 Weissler, Mark C. Schroeder, Lea Bender, Noemi Pawlita, Michael Thomas, Steve Pring, Miranda Dudding, Tom Kanterewicz, Beatriz Ferris, Robert Thomas, Sera Brhane, Yonathan Díez-Obrero, Virginia Milojevic, Maja Smith-Byrne, Karl Mariosa, Daniela Johansson, Mattias J. Herrero, Rolando Boccia, Stefania Cadoni, Gabriella Lacko, Martin Holcátová, Ivana Ahrens, Wolfgang Lagiou, Pagona Lagiou, Areti Polesel, Jerry Simonato, Lorenzo Merletti, Franco Healy, Claire M. Hansen, Bo T. Nygård, Mari Conway, David I. Wright, Sylvia Macfarlane, Tatiana V. Robinson, Max Alemany, Laia Agudo, Antonio Znaor, Ariana Amos, Christopher I. Waterboer, Tim Brennan, Paul |
author_sort | Ferreiro-Iglesias, Aida |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8511029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85110292021-10-29 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 Weissler, Mark C. Schroeder, Lea Bender, Noemi Pawlita, Michael Thomas, Steve Pring, Miranda Dudding, Tom Kanterewicz, Beatriz Ferris, Robert Thomas, Sera Brhane, Yonathan Díez-Obrero, Virginia Milojevic, Maja Smith-Byrne, Karl Mariosa, Daniela Johansson, Mattias J. Herrero, Rolando Boccia, Stefania Cadoni, Gabriella Lacko, Martin Holcátová, Ivana Ahrens, Wolfgang Lagiou, Pagona Lagiou, Areti Polesel, Jerry Simonato, Lorenzo Merletti, Franco Healy, Claire M. Hansen, Bo T. Nygård, Mari Conway, David I. Wright, Sylvia Macfarlane, Tatiana V. Robinson, Max Alemany, Laia Agudo, Antonio Znaor, Ariana Amos, Christopher I. Waterboer, Tim Brennan, Paul Nat Commun Article 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. Nature Publishing Group UK 2021-10-12 /pmc/articles/PMC8511029/ /pubmed/34642315 http://dx.doi.org/10.1038/s41467-021-26151-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article 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 Weissler, Mark C. Schroeder, Lea Bender, Noemi Pawlita, Michael Thomas, Steve Pring, Miranda Dudding, Tom Kanterewicz, Beatriz Ferris, Robert Thomas, Sera Brhane, Yonathan Díez-Obrero, Virginia Milojevic, Maja Smith-Byrne, Karl Mariosa, Daniela Johansson, Mattias J. Herrero, Rolando Boccia, Stefania Cadoni, Gabriella Lacko, Martin Holcátová, Ivana Ahrens, Wolfgang Lagiou, Pagona Lagiou, Areti Polesel, Jerry Simonato, Lorenzo Merletti, Franco Healy, Claire M. Hansen, Bo T. Nygård, Mari Conway, David I. Wright, Sylvia Macfarlane, Tatiana V. Robinson, Max Alemany, Laia Agudo, Antonio Znaor, Ariana Amos, Christopher I. Waterboer, Tim Brennan, Paul Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer |
title | Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer |
title_full | Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer |
title_fullStr | Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer |
title_full_unstemmed | Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer |
title_short | Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer |
title_sort | germline determinants of humoral immune response to hpv-16 protect against oropharyngeal cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511029/ https://www.ncbi.nlm.nih.gov/pubmed/34642315 http://dx.doi.org/10.1038/s41467-021-26151-9 |
work_keys_str_mv | AT ferreiroiglesiasaida germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT mckayjamesd germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT brennernicole germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT viranishama germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT lesseurcorina germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT gaborieauvalerie germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT nessandyr germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT hungrayjeanj germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT liugeoffrey germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT diergaardebrenda germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT olshanandrewf germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT hayesneil germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT weisslermarkc germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT schroederlea germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT bendernoemi germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT pawlitamichael germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT thomassteve germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT pringmiranda germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT duddingtom germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT kanterewiczbeatriz germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT ferrisrobert germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT thomassera germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT brhaneyonathan germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT diezobrerovirginia germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT milojevicmaja germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT smithbyrnekarl germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT mariosadaniela germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT johanssonmattiasj germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT herrerorolando germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT bocciastefania germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT cadonigabriella germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT lackomartin germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT holcatovaivana germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT ahrenswolfgang germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT lagioupagona germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT lagiouareti germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT poleseljerry germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT simonatolorenzo germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT merlettifranco germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT healyclairem germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT hansenbot germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT nygardmari germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT conwaydavidi germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT wrightsylvia germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT macfarlanetatianav germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT robinsonmax germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT alemanylaia germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT agudoantonio germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT znaorariana germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT amoschristopheri germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT waterboertim germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer AT brennanpaul germlinedeterminantsofhumoralimmuneresponsetohpv16protectagainstoropharyngealcancer |