{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:03:24Z","timestamp":1791500604329,"version":"4.3.4"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp; Neck"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Human papillomavirus (HPV) is an increasing risk factor for cancer. HPV\u2010associated oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favorable outcome. Blockstaining for p16 is a surrogate marker for HPV+ OPSCC. In oral and laryngeal squamous cell carcinoma (OSCC\/LSCC), the relevance of p16 immunohistochemistry, alone or in combination with other cell cycle\u2010related proteins, to identify HPV\u2010driven non\u2010OPSCC is less well understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We stained for p16, pRb, cyclin D1, and p53 in 327 HNSCC. In 310 OPSCC, HPV\u2010status was assessed by HPV DNA PCR. In 119 non\u2010OPSCC, RNA in situ hybridization was additionally performed. HPV\u2010status was correlated with staining patterns, p53 and clinical data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The OPSCC showed blockstaining for p16 in 36%, 8% were equivocal. Of these, HPV\u2010testing was performed in 57%, and 53% were positive for HPV DNA. HPV\u2010association correlated with absence of pRb and cyclin D1 and favorable outcome. In non\u2010OPSCC, 18% showed p16\u2010blockstaining, and 13% showed E6\/E7 RNA. Six of seven HPV+ OSCC and 8\/8 LSCC lost pRb and cyclin D1. Compared to HPV\u2010negative counterparts, patients with HPV+ cancers had lower rates of alcohol consumption and keratinizing morphology. HPV\u2010positive OSCC had a longer overall survival (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). HPV subtype 16 was the most common.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We conclude that HPV\u2010positive non\u2010OPSCC are associated with p16 overexpression and low levels of pRb and cyclin D1. High expression of pRb and cyclin D1 indicates HPV\u2010negativity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hed.27764","type":"journal-article","created":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T04:30:01Z","timestamp":1712723401000},"page":"2569-2581","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["p16 overexpression identifies oncogenic <scp>high\u2010risk HPV<\/scp> infection in <scp>non\u2010oropharyngeal<\/scp> squamous cell carcinoma of the head and neck"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8233-2986","authenticated-orcid":false,"given":"Anne\u2010Sophie","family":"Becker","sequence":"first","affiliation":[{"name":"Institute of Pathology Rostock University Medical Center  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Merkel","sequence":"additional","affiliation":[{"name":"Institute of Pathology 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