{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:32:04Z","timestamp":1790127124865,"version":"4.0.1"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"5","funder":[{"DOI":"10.13039\/100030692","name":"Intramural Research Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100030692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA098803"],"award-info":[{"award-number":["R01 CA098803"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Human papillomavirus (HPV) type 16 E6 protein seropositivity accurately predicts oropharyngeal squamous cell carcinoma risk decades before diagnosis; but the biomarker\u2019s 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In a cohort study in Brazil, Mexico, and the United States, we calculated HPV-16 E6 seropositivity (median fluorescence intensity\u2009&amp;gt;\u20091000), 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 3997 men, 14 had HPV-16 E6 antibodies detected (seroprevalence\u2009=\u20090.35%, 95% CI\u2009=\u20090.19% to 0.59%; median fluorescence intensity\u2009=\u20092407 [IQR\u2009=\u20091325-5986]). Older age was associated with increased odds of HPV-16 E6 seropositivity (50-84\u2009years vs 18-29\u2009years odds ratio\u2009=\u200916.61, 95% CI\u2009=\u20092.20 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\u200a000. Seven men had 3 or more years of follow-up; all were persistently seropositive for 3\u2009years. One man was seropositive for 9 years but seroreverted at his exit visit. Oral HPV-16 DNA (prevalence\u2009=\u20091.13%) was associated with HPV-16 E6 seropositivity (odds ratio\u2009=\u200916.87, 95% CI\u2009=\u20093.35 to 69.55), but oral HPV-16 DNA positivity was not persistent over follow-up, even when HPV-16 E6 antibodies were persistently detected.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jnci\/djae326","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T03:43:36Z","timestamp":1733888616000},"page":"915-923","source":"Crossref","is-referenced-by-count":6,"title":["Natural history of HPV-16 E6 serology among cancer-free men in a multicenter longitudinal cohort study"],"prefix":"10.1093","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7064-4424","authenticated-orcid":false,"given":"Jaimie Z","family":"Shing","sequence":"first","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Rockville, MD 20850,","place":["United 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Heidelberg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0257-2363","authenticated-orcid":false,"given":"Allan","family":"Hildesheim","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Rockville, MD 20850,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7798-9772","authenticated-orcid":false,"given":"Sudhir","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5089-3666","authenticated-orcid":false,"given":"Bradley A","family":"Sirak","sequence":"additional","affiliation":[{"name":"Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center , Tampa, FL 33612,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8793-0766","authenticated-orcid":false,"given":"John","family":"Schussler","sequence":"additional","affiliation":[{"name":"Information Management Services , Silver Spring, MD 20705,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5483-6303","authenticated-orcid":false,"given":"Danping","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Rockville, MD 20850,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention, National Cancer Institute, National Institutes 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