{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T17:52:20Z","timestamp":1763747540016,"version":"3.37.3"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,8,23]],"date-time":"2016-08-23T00:00:00Z","timestamp":1471910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA008748"],"award-info":[{"award-number":["P30CA008748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>In the current study, we aimed to examine primary parotid squamous cell carcinoma (Par<jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content>) for the presence of high\u2010risk human papillomavirus (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>) and associated molecular alterations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Eight cases of Par<jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content> were retrieved after a detailed clinicopathological review to exclude the possibility of metastasis and\/or extension from another primary site. <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> status was determined on the basis of immunohistochemistry (<jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>) for p16 expression and chromogenic <jats:italic>in\u2010situ<\/jats:italic> hybridization (<jats:styled-content style=\"fixed-case\">CISH<\/jats:styled-content>) for <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>. All cases were genotyped with a multiplexed mass spectrometry assay interrogating 91 hotspot mutations in eight cancer\u2010related genes (<jats:italic><jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content><\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">KRAS<\/jats:styled-content><\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">NRAS<\/jats:styled-content><\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content><\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">PIK<\/jats:styled-content>3<jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content><\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>1<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">MEK<\/jats:styled-content>1<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">ERBB<\/jats:styled-content>2<\/jats:italic>), and studied by fluorescence <jats:italic>in\u2010situ<\/jats:italic> hybridization for <jats:italic><jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content><\/jats:italic> copy number alteration. Three of eight cases (37.5%) were positive for the presence of <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> by <jats:styled-content style=\"fixed-case\">CISH<\/jats:styled-content> and p16 <jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>. One of three (33%) <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\u2010positive cases harboured a <jats:italic><jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content><\/jats:italic> hemizygous deletion, and one (33%) <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\u2010positive case harboured a <jats:italic><jats:styled-content style=\"fixed-case\">PIK<\/jats:styled-content>3<jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content><\/jats:italic> E545K somatic mutation. No alteration of the <jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K pathway was detected in <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\u2010negative tumours. Over a median follow\u2010up period of 66.2 months, only the patient with the <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>\u2010positive <jats:italic><jats:styled-content style=\"fixed-case\">PIK<\/jats:styled-content>3<jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content><\/jats:italic>\u2010mutated tumour died of his disease, the remaining seven patients being disease\u2010free.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Given the established aetiological role of <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> in other head and neck squamous cell carcinomas, it is likely that <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> represents an oncogenic driver in the pathogenesis of more than one\u2010third of Par<jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content>s. The presence of <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> in Par<jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content> may be coupled with alterations in the <jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K pathway. Further studies on <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> and the molecular characterization of a larger number of Par<jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content>s are needed to determine the clinical significance of these findings.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13027","type":"journal-article","created":{"date-parts":[[2016,7,4]],"date-time":"2016-07-04T05:54:34Z","timestamp":1467611674000},"page":"921-929","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A proportion of primary squamous cell carcinomas of the parotid gland harbour high\u2010risk human papillomavirus"],"prefix":"10.1111","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4638-9835","authenticated-orcid":false,"given":"Bin","family":"Xu","sequence":"first","affiliation":[{"name":"Department of 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