{"doi":"10.1016/j.ebiom.2020.103190","title":"HPV16 E6 seropositivity and oropharyngeal cancer: Marker of exposure, risk, or disease?","abstract":"Human papillomavirus (HPV) infection, primarily HPV16, is responsible for a substantial increase in the incidence of oropharyngeal cancers (base of tongue, tonsil, soft palate, and pharyngeal wall) among men in recent years in several developed countries [[1]Gillison M.L. Chaturvedi A.K. Anderson W.F. Fakhry C Epidemiology of human papillomavirus-positive head and neck squamous cell carcinoma.J Clin Oncol. 2015; 33: 3235-3242Crossref PubMed Scopus (564) Google Scholar]. Recent studies have discovered HPV16 E6 seropositivity (IgG antibodies measured through a Luminex-multiplexed assay) as a biomarker strongly associated with prospective oropharyngeal cancer risk [[2]Kreimer A.R. Ferreiro-Iglesias A. Nygard M. Bender N. Schroeder L. Hildesheim A. et al.Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium.Ann Oncol. 2019; 30: 1335-1343Summary Full Text Full Text PDF PubMed Scopus (26) Google Scholar,[3]Kreimer A.R. Johansson M. Yanik E.L. Katki H.A. Check D.P. Lang Kuhs K.A. et al.Kinetics of the human papillomavirus type 16 E6 antibody response prior to oropharyngeal cancer.J Natl Cancer Inst. 2017; 109Crossref Scopus (54) Google Scholar]. Yet, little is known regarding HPV16 E6 seroepidemiology in the general population. In the December issue of EBioMedicine, Brenner et al. [[4]Brenner N. Mentzer A.J. Hill M. Almond R. Allen N. Pawlita M. et al.Characterization of human papillomavirus (HPV) 16 E6 seropositive individuals without HPV-associated malignancies after 10 years of follow-up in the UK Biobank.EBioMedicine. 2020; 62103123Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar] report on the first large population-based study of HPV16 E6 seroepidemiology within the UK Biobank (ages 40–69 years). The key results include: 1) low prevalence of HPV16 E6 seropositivity (~0.8%); 2) seropositivity was associated with several markers of high-risk sexual behaviours; and 3) seropositivity was not associated with age, gender, or smoking status. Herein, we place the results of Brenner et al. [[4]Brenner N. Mentzer A.J. Hill M. Almond R. Allen N. Pawlita M. et al.Characterization of human papillomavirus (HPV) 16 E6 seropositive individuals without HPV-associated malignancies after 10 years of follow-up in the UK Biobank.EBioMedicine. 2020; 62103123Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar] within the context of the field with respect to the biological/epidemiological meaning of HPV16 E6 seropositivity and the clinical implications for screening. Is E6 seropositivity a marker of exposure, risk, or disease? Brenner et al. [[4]Brenner N. Mentzer A.J. Hill M. Almond R. Allen N. Pawlita M. et al.Characterization of human papillomavirus (HPV) 16 E6 seropositive individuals without HPV-associated malignancies after 10 years of follow-up in the UK Biobank.EBioMedicine. 2020; 62103123Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar] report higher E6 seropositivity in individuals with a higher number of lifetime sex partners, same-gender sex partners, early sexual debut, and in those seropositive for other sexually transmitted infections. These associations imply E6 seropositivity is a marker of exposure, consistent with acquisition of HPV infections at multiple anatomic sites, primarily through sexual activity [[5]Schiffman M. Doorbar J. Wentzensen N. de Sanjose S. Fakhry C. Monk B.J. et al.Carcinogenic human papillomavirus infection.Nat Rev Dis Primers. 2016; 2: 16086Crossref PubMed Scopus (340) Google Scholar]. Serologic markers of HPV, such as L1 antibodies, generally indicate cumulative exposure invariant of the site (i.e., anogenital vs. oral) or duration of infection (i.e., short-term vs. long-term) [[5]Schiffman M. Doorbar J. Wentzensen N. de Sanjose S. Fakhry C. Monk B.J. et al.Carcinogenic human papillomavirus infection.Nat Rev Dis Primers. 2016; 2: 16086Crossref PubMed Scopus (340) Google Scholar]. By contrast, accumulating evidence suggests E6 an","journal":"EBioMedicine","year":2021,"id":204106,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9646,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":453584,"name":"Anil K. Chaturvedi","orcid":"0000-0003-2696-8899","position":1,"is_corresponding":false},{"id":420942,"name":"Rebecca Landy","orcid":"0000-0003-4042-4820","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:51:22.166488Z","pmid":"33418506","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}