{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T09:05:27Z","timestamp":1784538327372,"version":"3.55.0"},"reference-count":23,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Oropharyngeal squamous cell carcinoma (OPSCC) is a biologically heterogeneous disease. p16 immunohistochemistry is widely used as a surrogate marker for human papillomavirus (HPV)\u2013associated OPSCC and plays a key role in prognostication and staging. However, p16 overexpression does not invariably reflect transcriptionally active HPV infection, and the clinical significance of p16\u2013HPV discordance remains incompletely defined, particularly in populations with high exposure to traditional carcinogens. Materials and Methods: We conducted a retrospective cohort study of patients diagnosed with OPSCC between 2016 and 2020 at a tertiary referral center in Taiwan. p16 immunohistochemistry was performed in all cases, and transcriptionally active high-risk HPV was assessed by RNA in situ hybridization in p16-positive tumors. Clinicopathologic characteristics, carcinogen exposure profiles, and survival outcomes, including overall survival (OS) and disease-free survival (DFS), were analyzed according to p16 and HPV status. Results: Among 140 patients with OPSCC, 49 (35%) were p16-positive, of whom 44 (90%) demonstrated transcriptionally active HPV. Compared with p16-negative tumors, p16-positive OPSCC was significantly associated with lymphoepithelial organ involvement, non-keratinizing morphology, lower clinical stage, and less exposure to alcohol, betel nut, and tobacco. In Kaplan\u2013Meier and univariable analyses, p16 positivity was associated with significantly improved OS and DFS. In contrast, p16-positive\/HPV RNA-negative tumors exhibited clinicopathologic features more closely resembling p16-negative OPSCC, including greater keratinization and higher carcinogen exposure. Conclusions: p16-positive\/HPV RNA-negative tumors showed clinicopathologic features suggestive of biological heterogeneity; however, the small number of discordant cases precludes definitive conclusions regarding survival differences. These findings support selective HPV RNA testing in p16-positive OPSCC with atypical clinicopathologic features, particularly in carcinogen-endemic populations.<\/jats:p>","DOI":"10.3390\/medicina62071401","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T07:54:13Z","timestamp":1784534053000},"page":"1401","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic Implications of p16 Immunohistochemistry and Its Discordance with Transcriptionally Active HPV in Oropharyngeal Squamous Cell Carcinoma: A Taiwanese Cohort Study"],"prefix":"10.3390","volume":"62","author":[{"given":"Yun-An","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Kuan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kuang-Tien General Hospital, Shalu, Taichung 433, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4299-2784","authenticated-orcid":false,"given":"Jen-Fan","family":"Hang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei 40705, Taiwan"},{"name":"School of Medicine and Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6508-6448","authenticated-orcid":false,"given":"Chien-Chih","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung 40705, Taiwan"},{"name":"Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung 40705, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","unstructured":"WHO Classification of Tumours Editorial Board (2024). 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Agents Cancer"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/7\/1401\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T08:28:28Z","timestamp":1784536108000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/7\/1401"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":23,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["medicina62071401"],"URL":"https:\/\/doi.org\/10.3390\/medicina62071401","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]}}}