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Premalignant stages in cervical cancer have been studied extensively, while little is known about premalignant stages in TSCC\/BOTSCC and the role of HPV. Here we analyzed differences in gene and protein expression between high\u2010grade dysplasia and invasive cancer in both HPV\u2010positive (HPV<jats:sup>+<\/jats:sup>) and HPV\u2010negative (HPV<jats:sup>\u2212<\/jats:sup>) TSCC\/BOTSCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>High\u2010grade dysplasia and invasive carcinoma were laser microdissected from HPV<jats:sup>+<\/jats:sup> and HPV<jats:sup>\u2212<\/jats:sup> TSCC\/BOTSCC tumor sections. Differential gene expression was studied utilizing nanoString RNA\u2010panels and genes of interest were validated on the protein level by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty genes in the HPV<jats:sup>+<\/jats:sup> tumors showed significantly different expression between high\u2010grade dysplasia and invasive cancer and 33 genes in the HPV<jats:sup>\u2212<\/jats:sup> tumors. Five out of the nine most significant pathways showed similar increased activity in invasive cancer as compared to high\u2010grade dysplasia in both HPV<jats:sup>+<\/jats:sup> and HPV<jats:sup>\u2212<\/jats:sup> tumors. Lastly, significant differences in protein expression was confirmed for SPARC, psoriasin, type I collagen and galectin\u20101 in both HPV<jats:sup>+<\/jats:sup> and HPV<jats:sup>\u2212<\/jats:sup> tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This is to our knowledge the first study disclosing differences and similarities in gene expression between dysplastic and invasive HPV<jats:sup>+<\/jats:sup> and HPV<jats:sup>\u2212<\/jats:sup> TSCC\/BOTSCC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.2450","type":"journal-article","created":{"date-parts":[[2019,8,27]],"date-time":"2019-08-27T15:47:44Z","timestamp":1566920864000},"page":"6221-6232","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Differences in gene expression between high\u2010grade dysplasia and invasive HPV<sup>+<\/sup> and HPV<sup>\u2212<\/sup> tonsillar and base of tongue cancer"],"prefix":"10.1002","volume":"8","author":[{"given":"Linnea","family":"Haeggblom","sequence":"first","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institute Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"\u00c4hrlund\u2010Richter","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institute Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Mirzaie","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institute Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Farrajota Neves da Silva","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institute Stockholm Sweden"},{"name":"Department of Clinical Pathology Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona G.","family":"Ursu","sequence":"additional","affiliation":[{"name":"Department of Microbiology University of Medicine and Pharmacy Grigore T. 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