{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:25:50Z","timestamp":1793647550026,"version":"4.5.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T00:00:00Z","timestamp":1707782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23DE029811"],"award-info":[{"award-number":["K23DE029811"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03DE030550"],"award-info":[{"award-number":["R03DE030550"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21CA267152"],"award-info":[{"award-number":["R21CA267152"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03DE030550"],"award-info":[{"award-number":["R03DE030550"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K07CA218247"],"award-info":[{"award-number":["K07CA218247"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01CA249992-01A1"],"award-info":[{"award-number":["1R01CA249992-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01CA220581-01A1"],"award-info":[{"award-number":["1R01CA220581-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA068485"],"award-info":[{"award-number":["P30CA068485"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["# W81XWH2110160"],"award-info":[{"award-number":["# W81XWH2110160"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["# RES516237"],"award-info":[{"award-number":["# RES516237"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Vanderbilt Tissue Pathology Shared Resource"},{"name":"Shared Instrumentation","award":["S10 OD023475-01A1"],"award-info":[{"award-number":["S10 OD023475-01A1"]}]},{"name":"Shared Instrumentation","award":["S10 OD016355"],"award-info":[{"award-number":["S10 OD016355"]}]},{"name":"Leica Bond RX"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>In this feasibility study, we explored the combined use of circulating tumor human papillomavirus (HPV) DNA (ctHPVDNA) and HPV serology as diagnostic tests for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Among patients with research-banked serum or plasma at diagnosis, IgG antibodies to oncoproteins from HPV types 16, 18, 31, 33, 35, 45, 52, and 58 were detected with multiplex serology. Positivity for HPV 16 was defined based on detection of combinations of anti-E6, E1, E2, and E7 and for other high-risk types on detection of anti-E6 and anti-E7. Circulating tumor HPV DNA was detected by custom digital droplet polymerase chain reaction (ddPCR) assays for HPV types 16, 18, 33, 35, and 45. p16 immunohistochemistry and high-risk HPV RNA in situ hybridization (ISH) using a cocktail of 18 high-risk HPV types were performed on tissue.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 75 patients, 67 (89.3%) were HPV-associated (p16 and HPV RNA ISH positive) and 8 (10.7%) were HPV-independent. All 8 HPV-independent patients were seronegative and negative for ctHPVDNA (100% specificity). Serology was positive in 53 (79.1%) of 67 HPV-associated patients, while ddPCR was positive for ctHPVDNA in 59 (88.6%) of 67 HPV-associated patients. Requiring both tests to be positive resulted in a sensitivity of 50 (74.6%) of 67 while combining assays (either positive) improved sensitivity to 62 (92.6%) of 67.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Compared to HPV RNA ISH, HPV serology and ctHPVDNA are sensitive and highly specific biomarkers for HPV-associated OPSCC at the time of presentation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajcp\/aqad185","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T16:37:33Z","timestamp":1707842253000},"page":"570-578","source":"Crossref","is-referenced-by-count":13,"title":["Assessing the feasibility of a multimodal liquid biopsy for the diagnosis of HPV-associated oropharyngeal squamous cell carcinoma"],"prefix":"10.1093","volume":"161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9002-1283","authenticated-orcid":false,"suffix":"Jr","given":"James S","family":"Lewis","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology and Vanderbilt University Medical Center , Nashville, TN ,","place":["US"]},{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, Vanderbilt University Medical Center , Nashville, TN ,","place":["US"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Naegele","sequence":"additional","affiliation":[{"name":"Mass Eye and Ear , Boston, MA ,","place":["US"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios","family":"Efthymiou","sequence":"additional","affiliation":[{"name":"Mass Eye and Ear , Boston, MA ,","place":["US"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4180-8180","authenticated-orcid":false,"given":"Mitra","family":"Mehrad","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology and Vanderbilt University Medical Center , Nashville, TN ,","place":["US"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim A","family":"Ely","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology and Vanderbilt University Medical Center , Nashville, TN ,","place":["US"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Waterboer","sequence":"additional","affiliation":[{"name":"Division of Infections and Cancer Epidemiology, German Cancer Research Center (DFKZ) , Heidelberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystle A","family":"Lang Kuhs","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Environmental Health, College of Public Health and"},{"name":"Markey Cancer Center, University of Kentucky , Lexington, KY ,","place":["US"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth J","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, Vanderbilt University Medical Center , Nashville, TN ,","place":["US"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7609-737X","authenticated-orcid":false,"given":"Kelsey","family":"Richard","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine , Nashville, TN ,","place":["US"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipon","family":"Das","sequence":"additional","affiliation":[{"name":"Mass Eye and Ear , Boston, MA ,","place":["US"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5284-7762","authenticated-orcid":false,"given":"Daniel L","family":"Faden","sequence":"additional","affiliation":[{"name":"Mass Eye and Ear , Boston, MA ,","place":["US"]},{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, Harvard Medical School , Boston, MA ,","place":["US"]},{"name":"Broad Institute of the Massachusetts Institute of Technology and Harvard University , Cambridge, MA ,","place":["US"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,13]]},"reference":[{"key":"2025021301020403200_CIT0001","first-page":"24","article-title":"Human papillomavirus and survival of patients with oropharyngeal cancer","volume-title":"N Engl J Med.","author":"Ang","year":"2010"},{"key":"2025021301020403200_CIT0002","first-page":"744","article-title":"Human papillomavirus-associated head and neck cancer is a 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