Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.
Aged
Antibodies, Viral
/ biosynthesis
Capsid Proteins
/ genetics
Case-Control Studies
Female
Gene Expression
Genetic Predisposition to Disease
Genome-Wide Association Study
HLA Antigens
/ classification
Haplotypes
Human papillomavirus 16
/ immunology
Humans
Immunity, Humoral
Male
Meta-Analysis as Topic
Middle Aged
Mouth Neoplasms
/ genetics
Oncogene Proteins, Viral
/ genetics
Oropharyngeal Neoplasms
/ genetics
Papillomavirus Infections
/ genetics
Quantitative Trait Loci
Repressor Proteins
/ genetics
Risk Factors
Smoking
/ physiopathology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 10 2021
12 10 2021
Historique:
received:
04
12
2020
accepted:
13
09
2021
entrez:
13
10
2021
pubmed:
14
10
2021
medline:
4
11
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34642315
doi: 10.1038/s41467-021-26151-9
pii: 10.1038/s41467-021-26151-9
pmc: PMC8511029
doi:
Substances chimiques
Antibodies, Viral
0
Capsid Proteins
0
E6 protein, Human papillomavirus type 16
0
HLA Antigens
0
Oncogene Proteins, Viral
0
Repressor Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5945Subventions
Organisme : NCI NIH HHS
ID : R01 CA092039
Pays : United States
Organisme : Department of Health
ID : RP-PG-0707-10034
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA047904
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA090731
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA097190
Pays : United States
Organisme : Medical Research Council
ID : MR/N005872/1
Pays : United Kingdom
Organisme : NIDCR NIH HHS
ID : R01 DE025712
Pays : United States
Organisme : Cancer Research UK
ID : C18281/A19169
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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