{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T16:18:58Z","timestamp":1776701938481,"version":"3.51.2"},"reference-count":21,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T00:00:00Z","timestamp":1455580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2016,4,15]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The incidence of p16 overexpression and the role of human papillomavirus (HPV) in cutaneous head and neck squamous cell carcinoma (cHNSCC) are unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>One hundred forty\u2010three patients with cHNSCC lymph node metastases involving the parotid gland were evaluated for p16 expression by immunohistochemistry. The detection of 18 high\u2010risk HPV subtypes was performed with HPV RNA in situ hybridization for a subset of 59 patients. The results were correlated with clinicopathological features and outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The median follow\u2010up time was 5.3 years. No differences were observed in clinicopathological factors with respect to the p16 status. p16 was positive, weak, and negative in 45 (31%), 21 (15%), and 77 cases (54%), respectively. No high\u2010risk HPV subtypes were identified, regardless of the p16 status. The p16 status was not prognostic for overall (hazard ratio, 1.08; 95% confidence interval [CI], 0.85\u20101.36; <jats:italic>P<\/jats:italic> = .528), cancer\u2010specific (hazard ratio, 1.12; 95% CI, 0.77\u20101.64; <jats:italic>P<\/jats:italic> = .542), or progression\u2010free survival (hazard ratio, 1.03; 95% CI, 0.83\u20101.29; <jats:italic>P<\/jats:italic> = .783). Distant metastasis\u2010free survival, freedom from locoregional failure, and freedom from local failure were also not significantly associated with the p16 status.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>p16 positivity is common but not prognostic in cHNSCC lymph node metastases. High\u2010risk HPV subtypes are not associated with p16 positivity and do not appear to play a role in this disease. HPV testing, in addition to the p16 status in the unknown primary setting, may provide additional information for determining a putative primary site. <jats:bold><jats:italic>Cancer<\/jats:italic> 2016;122:1201\u20138<\/jats:bold>. \u00a9 <jats:italic>2016 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.29901","type":"journal-article","created":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T11:27:17Z","timestamp":1455622037000},"page":"1201-1208","source":"Crossref","is-referenced-by-count":40,"title":["p16\u2010positive lymph node metastases from cutaneous head and neck squamous cell carcinoma: No association with high\u2010risk human papillomavirus or prognosis and implications for the workup of the unknown primary"],"prefix":"10.1002","volume":"122","author":[{"given":"Lachlan J.","family":"McDowell","sequence":"first","affiliation":[{"name":"Division of Radiation Oncology and Cancer Imaging Peter MacCallum Cancer Centre Melbourne Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Young","sequence":"additional","affiliation":[{"name":"Research Division Peter MacCallum Cancer Centre Melbourne Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meredith L.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology and Cancer Imaging Peter MacCallum Cancer Centre Melbourne Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tze\u2010Jian","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology and Cancer Imaging Peter MacCallum Cancer Centre Melbourne Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Kleid","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology Peter MacCallum Cancer Centre Melbourne Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen S.","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology and Cancer Imaging Peter MacCallum Cancer Centre Melbourne Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias","family":"Bressel","sequence":"additional","affiliation":[{"name":"Centre for Biostatistics and Clinical Trials Peter MacCallum Cancer Centre Melbourne Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Estall","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology and Cancer Imaging Peter MacCallum Cancer Centre Melbourne Australia"},{"name":"University of Melbourne Parkville Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danny","family":"Rischin","sequence":"additional","affiliation":[{"name":"University of Melbourne Parkville Australia"},{"name":"Department of Medical Oncology Peter MacCallum Cancer Centre Melbourne Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Solomon","sequence":"additional","affiliation":[{"name":"Research Division Peter MacCallum Cancer Centre Melbourne Australia"},{"name":"University of Melbourne Parkville Australia"},{"name":"Department of Medical Oncology Peter MacCallum Cancer Centre Melbourne Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"June","family":"Corry","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology and Cancer Imaging Peter MacCallum Cancer Centre Melbourne Australia"},{"name":"University of Melbourne Parkville Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,2,16]]},"reference":[{"key":"e_1_2_7_2_1","series-title":"Cancer Series","volume-title":"Non\u2010Melanoma Skin Cancer: General Practice Consultations, Hospitalisations and Mortality","author":"Australian Institute of Health and 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