{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T18:54:29Z","timestamp":1779216869134,"version":"3.51.4"},"reference-count":54,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2013,10,21]],"date-time":"2013-10-21T00:00:00Z","timestamp":1382313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Dutch Cancer Foundation","award":["2007-3935"],"award-info":[{"award-number":["2007-3935"]}]},{"name":"Medical Research Foundation, Maastricht University Medical Centre","award":["PF126"],"award-info":[{"award-number":["PF126"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:p>Human papillomavirus (HPV) is a risk factor for the development of benign and malignant mucosal head and neck lesions. P16<jats:sup>INK4A<\/jats:sup> is often used as a surrogate marker for HPV\u2010infection, although there is still controversy with respect its reliability. Our aim was to determine if p16<jats:sup>INK4A<\/jats:sup> overexpression can accurately predict both high\u2010risk and low\u2010risk\u2010HPV\u2010presence in (pre)malignant and benign head and neck lesions. P16<jats:sup>INK4A<\/jats:sup> immunohistochemistry was performed on paraffin\u2010embedded tissue sections of 162 oropharyngeal squamous cell carcinomas (OPSCC), 14 tonsillar and 23 laryngeal dysplasias, and 20 tonsillar and 27 laryngeal papillomas. PCR, enzyme\u2010immunoassay and FISH analysis were used to assess HPV\u2010presence and type. Of the 162 OPSCC and 14 tonsillar dysplasias, 51 (31%) and 10 (71%) were HPV16\u2010positive, respectively. All tonsillar papillomas were HPV\u2010negative and four laryngeal dysplasias and 26 laryngeal papillomas were positive for HPV6 or \u221211. P16<jats:sup>INK4A<\/jats:sup> immunohistochemistry revealed a strong nuclear and cytoplasmic staining in 50 out of 51 HPV16\u2010positive and 5 out of 111 HPV\u2010negative OPSCC (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) and in all HPV16\u2010positive tonsillar dysplasias, whereas highly variable staining patterns were detected in the papillomas and laryngeal dysplasias, irrespective of the HPV\u2010status. In addition, the latter lesions generally showed a higher nuclear than cytoplasmic p16<jats:sup>INK4A<\/jats:sup> immunostaining intensity. In conclusion, our data show that strong nuclear and cytoplasmic p16<jats:sup>INK4A<\/jats:sup> overexpression is a reliable surrogate indicator for HPV16 in OPSCC and (adjacent) dysplasias. For HPV6 or \u221211\u2010positive and HPV\u2010negative benign and premalignant lesions of the tonsil and larynx, however, p16<jats:sup>INK4A<\/jats:sup> immunostaining is highly variable and cannot be recommended to predict HPV\u2010presence.<\/jats:p>","DOI":"10.1002\/ijc.28534","type":"journal-article","created":{"date-parts":[[2013,10,14]],"date-time":"2013-10-14T11:42:27Z","timestamp":1381750947000},"page":"2108-2117","source":"Crossref","is-referenced-by-count":65,"title":["P16<sup>INK4A<\/sup> immunostaining is a strong indicator for high\u2010risk\u2010HPV\u2010associated oropharyngeal carcinomas and dysplasias, but is unreliable to predict low\u2010risk\u2010HPV\u2010infection in head and neck papillomas and laryngeal dysplasias"],"prefix":"10.1002","volume":"134","author":[{"given":"Jeroen J.","family":"Mooren","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, GROW\u2010School for Oncology and Developmental Biology Maastricht University Medical Centre  The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sibel E.","family":"G\u00fcltekin","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Faculty of Dentistry Gazi University Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos M.J.A.A.","family":"Straetmans","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, GROW\u2010School for Oncology and Developmental Biology Maastricht University Medical Centre  The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annick","family":"Haesevoets","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, GROW\u2010School for Oncology and Developmental Biology Maastricht University Medical Centre  The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carine J.","family":"Peutz\u2010Kootstra","sequence":"additional","affiliation":[{"name":"Department of Pathology, GROW\u2010School for Oncology and Developmental Biology Maastricht University Medical Centre  The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian U.","family":"Huebbers","sequence":"additional","affiliation":[{"name":"Jean\u2010Uhrmacher\u2010Institute for Otorhinolaryngological Research University of Cologne  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans P.","family":"Dienes","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Cologne  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Wieland","sequence":"additional","affiliation":[{"name":"Institute for Virology, University of Cologne  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frans 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