Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.
case_control · Level III
Where this comes from
- Record sourced from PubMed, PMID 34642315.
- Also identified by DOI 10.1038/s41467-021-26151-9 and PMC identifier 8511029.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- HLA Antigens
- Human papillomavirus 16
- Immunity, Humoral
- Mouth Neoplasms
- Oropharyngeal Neoplasms
- Papillomavirus Infections