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Hundred and twenty cancer cases were from the oropharynx and 94 were from head and neck cancer regions outside the oropharynx (45 oral cavity, 12 hypopharynx and 35 larynx). Serum antibodies to early (E1, E2, E6 and E7) and late (L1) HPV16 proteins were analyzed by multiplex serology and were compared to tumor HPV RNA status as the gold standard. A tumor was defined as HPV\u2010driven in the presence of HPV16 DNA and HPV16 transformation\u2010specific RNA transcript patterns (E6*I, E1<jats:sup>\u2227<\/jats:sup>E4 and E1C). Of 120 OPSCC, 66 (55%) were HPV16\u2010driven. HPV16 E6 seropositivity was the best predictor of HPV16\u2010driven OPSCC (diagnostic accuracy 97% [95%CI 92\u201399%], Cohen's kappa 0.93 [95%CI 0.8\u20131.0]). Of the 66 HPV\u2010driven OPSCC, 63 were HPV16 E6 seropositive, compared to only one (1.8%) among the 54 non\u2010HPV\u2010driven OPSCC, resulting in a sensitivity of 96% (95%CI 88\u201398) and a specificity of 98% (95%CI 90\u2013100). Of 94 HNSCC outside the oropharynx, six (6%) were HPV16\u2010driven. In these patients, HPV16 E6 seropositivity had lower sensitivity (50%, 95%CI 19\u201381), but was highly specific (100%, 95%CI 96\u2013100). In conclusion, HPV16 E6 seropositivity appears to be a highly reliable diagnostic marker for HPV16\u2010driven OPSCC with very high sensitivity and specificity, but might be less sensitive for HPV16\u2010driven HNSCC outside the oropharynx.<\/jats:p>","DOI":"10.1002\/ijc.30697","type":"journal-article","created":{"date-parts":[[2017,3,19]],"date-time":"2017-03-19T05:58:57Z","timestamp":1489903137000},"page":"2748-2757","source":"Crossref","is-referenced-by-count":118,"title":["Sensitivity and specificity of antibodies against HPV16 E6 and other early proteins for the detection of HPV16\u2010driven oropharyngeal squamous cell carcinoma"],"prefix":"10.1002","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5010-5236","authenticated-orcid":false,"given":"Dana","family":"Holzinger","sequence":"first","affiliation":[{"name":"Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program German Cancer Research Center (DKFZ) Heidelberg 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Neurosciences ENT Clinic and Regional Center for Head and Neck Cancer, University of Padua Treviso Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christel","family":"Herold\u2010Mende","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Heidelberg University Heidelberg Germany"},{"name":"Department of Neurosurgery, Division of Experimental Neurosurgery Heidelberg University Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Dyckhoff","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Heidelberg University Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Boehm","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology University Hospital Leipzig Leipzig 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