{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T17:24:46Z","timestamp":1781285086892,"version":"3.54.1"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,8,19]],"date-time":"2014-08-19T00:00:00Z","timestamp":1408406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:p>p16<jats:sup>INK4a<\/jats:sup> immunohistochemical overexpression is an overall reliable surrogate marker of human papillomavirus (HPV)\u2010associated head and neck squamous cell carcinomas (HNSCC). However, cases of ambiguous p16<jats:sup>INK4a<\/jats:sup> overexpression are regularly detected in the head and neck: p16<jats:sup>INK4a<\/jats:sup> expression can be observed in non\u2010malignant tissue, such as tonsillar crypt epithelium and a proportion of branchial cleft cysts. Additionally, diverse patterns of p16<jats:sup>INK4<\/jats:sup> expression can complicate interpretation of \u201cp16<jats:sup>INK4a<\/jats:sup>\u2010positivity\u201d. These aspects impede the unrestricted application of p16<jats:sup>INK4a<\/jats:sup> as a diagnostic marker in the head and neck. We hypothesized that combined detection of p16<jats:sup>INK4a<\/jats:sup> and the proliferation marker Ki\u201067 could support clarification of ambiguous p16<jats:sup>INK4a<\/jats:sup> expression in the head and neck by specifically indicating p16<jats:sup>INK4a<\/jats:sup>\u2010expressing cells with proliferative activity. p16<jats:sup>INK4a<\/jats:sup>\/Ki\u201067 co\u2010expression in a combined staining procedure was correlated to distinct p16<jats:sup>INK4a<\/jats:sup> expression patterns and HPV status (HPV DNA followed by E6*I oncogene mRNA detection) in 147 HNSCC and 50 non\u2010malignant head and neck samples. p16<jats:sup>INK4a<\/jats:sup>\/Ki\u201067 co\u2010expression only occurred in transformed cells of the head and neck. Co\u2010expression was never detected in non\u2010transformed cells. Combined p16<jats:sup>INK4a<\/jats:sup>\/Ki\u201067 expression was stringently associated with a diffuse p16<jats:sup>INK4a<\/jats:sup> expression pattern. All HPV oncogene\u2010expressing HNSCC showed p16<jats:sup>INK4a<\/jats:sup>\/Ki\u201067 co\u2010expression. We demonstrate that p16<jats:sup>INK4a<\/jats:sup>\/Ki\u201067 co\u2010expression occurs exclusively in transformed cells of the head and neck. Our findings indicate a substantial impact of combined p16<jats:sup>INK4a<\/jats:sup>\/Ki\u201067 expression in the assessment of ambiguous p16<jats:sup>INK4a<\/jats:sup> expression in the head and neck by specifically identifying p16<jats:sup>INK4a<\/jats:sup>\u2010expressing cells with proliferative activity. This property will be of considerable significance for head and neck histo\u2010 and cytopathology.<\/jats:p>","DOI":"10.1002\/ijc.29130","type":"journal-article","created":{"date-parts":[[2014,8,19]],"date-time":"2014-08-19T06:05:22Z","timestamp":1408428322000},"page":"1589-1599","source":"Crossref","is-referenced-by-count":42,"title":["p16<sup>INK4a<\/sup>\/Ki\u201067 co\u2010expression specifically identifies transformed cells in the head and neck region"],"prefix":"10.1002","volume":"136","author":[{"given":"Elena\u2010Sophie","family":"Prigge","sequence":"first","affiliation":[{"name":"Department of Applied Tumor Biology Institute of Pathology, University of Heidelberg, and Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csaba","family":"Toth","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Heidelberg, and National Center 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