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Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer
A. Ferreiro-Iglesias, JD. McKay, N. Brenner, S. Virani, C. Lesseur, V. Gaborieau, AR. Ness, RJ. Hung, G. Liu, B. Diergaarde, AF. Olshan, N. Hayes, MC. Weissler, L. Schroeder, N. Bender, M. Pawlita, S. Thomas, M. Pring, T. Dudding, B. Kanterewicz,...
Language English Country Great Britain
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
R01 CA092039
NCI NIH HHS - United States
RP-PG-0707-10034
Department of Health - United Kingdom
P30 CA047904
NCI NIH HHS - United States
R01 CA090731
NCI NIH HHS - United States
P50 CA097190
NCI NIH HHS - United States
R01 DE025712
NIDCR NIH HHS - United States
C18281/A19169
Cancer Research UK - United Kingdom
NLK
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- MeSH
- Genome-Wide Association Study MeSH
- Gene Expression MeSH
- Genetic Predisposition to Disease MeSH
- Haplotypes MeSH
- HLA Antigens classification genetics immunology MeSH
- Immunity, Humoral * MeSH
- Papillomavirus Infections genetics immunology pathology virology MeSH
- Smoking physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Human papillomavirus 16 immunology pathogenicity MeSH
- Quantitative Trait Loci MeSH
- Meta-Analysis as Topic MeSH
- Oropharyngeal Neoplasms genetics immunology pathology virology MeSH
- Mouth Neoplasms genetics immunology pathology virology MeSH
- Oncogene Proteins, Viral genetics immunology MeSH
- Antibodies, Viral biosynthesis MeSH
- Repressor Proteins genetics immunology MeSH
- Risk Factors MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Capsid Proteins genetics immunology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
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.
Bristol Dental School University of Bristol Bristol UK
Cancer Registry of Norway Oslo Norway
Catalan Institute of Oncology IDIBELL Barcelona Spain
Centre for Oral Health Research Newcastle University Newcastle UK
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública CIBERESP Madrid Spain
CeRMS and University of Turin Turin Italy
Department of Medicine Baylor College of Medicine Houston TX USA
Department of Research Cancer Registry of Norway Oslo Norway
Infections and Cancer Epidemiology German Cancer Research Center Heidelberg Germany
Institute of Hygiene and Epidemiology Prague Czech Republic
National Cancer Institute IRCCS Aviano Italy
Oncology Data Analytics Program Catalan Institute of Oncology Barcelona Spain
Queen Elizabeth University Hospital NHS Greater Glasgow and Clyde Glasgow UK
School of Medicine Dentistry and Nursing University of Glasgow Glasgow UK
School of Medicine National and Kapodistrian University of Athens Athens Greece
School of Public Health University of West Attica Athens Greece
Trinity College School of Dental Science Dublin Ireland
University Bremen Bremen Germany
University of Aberdeen Aberdeen UK
References provided by Crossref.org
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