{"doi":"10.1093/jnci/djae326","title":"Natural history of HPV-16 E6 serology among cancer-free men in a multicenter longitudinal cohort study","abstract":"BACKGROUND: Human papillomavirus (HPV) type 16 E6 protein seropositivity accurately predicts oropharyngeal squamous cell carcinoma risk decades before diagnosis; but the biomarker's translational potential is unknown. To inform considerations for oropharyngeal squamous cell carcinoma screening, we described HPV-16 E6 seroprevalence, predictors, and kinetics among cancer-free men. METHODS: In a cohort study in Brazil, Mexico, and the United States, we calculated HPV-16 E6 seropositivity (median fluorescence intensity > 1000), measured by multiplex serology, in cancer-free men. We assessed HPV-16 E6 seropositivity predictors using logistic regression, adjusting for country, age, sexual orientation, and lifetime number of sexual partners. Among HPV-16 E6 seropositive men, we retrieved all available retrospective serum samples and described temporal HPV-16 E6 antibody patterns. RESULTS: Of 3997 men, 14 had HPV-16 E6 antibodies detected (seroprevalence = 0.35%, 95% CI = 0.19% to 0.59%; median fluorescence intensity = 2407 [IQR = 1325-5986]). Older age was associated with increased odds of HPV-16 E6 seropositivity (50-84 years vs 18-29 years odds ratio = 16.61, 95% CI = 2.20 to 417.03). Serum from 11 of the 14 seropositive men retested positive; 6 men had median fluorescence intensity above 5000, of whom 2 had median fluorescence intensity greater than 10 000. Seven men had 3 or more years of follow-up; all were persistently seropositive for 3 years. One man was seropositive for 9 years but seroreverted at his exit visit. Oral HPV-16 DNA (prevalence = 1.13%) was associated with HPV-16 E6 seropositivity (odds ratio = 16.87, 95% CI = 3.35 to 69.55), but oral HPV-16 DNA positivity was not persistent over follow-up, even when HPV-16 E6 antibodies were persistently detected. CONCLUSION: Although HPV-16 E6 seropositivity is rare, it is generally stable once detected; thus, HPV-16 E6 antibodies may be an informative biomarker of HPV-driven oropharyngeal squamous cell carcinoma. Few men seroreverted following HPV-16 E6 seropositivity but remained close to the seropositivity cutoff; thus, cancer risk among these men is less clear.","journal":"JNCI Journal of the National Cancer Institute","year":2024,"id":448037,"datarank":0.33675674014271273,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.044870217784415675,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.044870217784415675,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":6,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.6688,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":390461,"name":"Anna R. Giuliano","orcid":"0000-0002-5440-8859","position":1,"is_corresponding":false},{"id":558766,"name":"Nicole Brenner","orcid":"0000-0002-7690-4925","position":2,"is_corresponding":false},{"id":1266673,"name":"Birgitta E. Michels","orcid":"0000-0001-9948-4567","position":3,"is_corresponding":false},{"id":265756,"name":"Allan Hildesheim","orcid":"0000-0003-0257-2363","position":4,"is_corresponding":false},{"id":77400,"name":"Sudhir Srivastava","orcid":"0000-0002-7798-9772","position":5,"is_corresponding":false},{"id":407870,"name":"Bradley Sirak","orcid":null,"position":6,"is_corresponding":false},{"id":265759,"name":"John Schussler","orcid":"0000-0002-8793-0766","position":7,"is_corresponding":false},{"id":388041,"name":"Danping Liu","orcid":"0000-0001-5483-6303","position":8,"is_corresponding":false},{"id":1266674,"name":"Wendy Wang","orcid":"0009-0007-8630-2796","position":9,"is_corresponding":false},{"id":390102,"name":"Tim Waterboer","orcid":"0000-0002-0616-6963","position":10,"is_corresponding":false},{"id":265766,"name":"Aimée R. Kreimer","orcid":"0000-0002-6073-2591","position":11,"is_corresponding":false},{"id":521810,"name":"Jaimie Z. Shing","orcid":"0000-0001-7064-4424","position":0,"is_corresponding":true}],"reference_count":21,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:02:08.018689Z","pmid":"39658222","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":[]}