{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T01:29:26Z","timestamp":1771464566766,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,3,25]],"date-time":"2018-03-25T00:00:00Z","timestamp":1521936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Cancer Society in Stockholm","award":["151253"],"award-info":[{"award-number":["151253"]}]},{"name":"Stockholm County ALF","award":["20160292"],"award-info":[{"award-number":["20160292"]}]},{"name":"The Swedish Cancer Society","award":["160259"],"award-info":[{"award-number":["160259"]}]},{"DOI":"10.13039\/501100009745","name":"Emil och Wera Cornells Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009745","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Swedish Cancer and Allergy Foundation","award":["73"],"award-info":[{"award-number":["73"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human papillomavirus (HPV) is a major etiological factor for tonsillar and the base of tongue cancer (TSCC\/BOTSCC). HPV-positive and HPV-negative TSCC\/BOTSCC present major differences in mutations, mRNA expression and clinical outcome. Earlier protein studies on TSCC\/BOTSCC have mainly analyzed individual proteins. Here, the aim was to compare a larger set of cancer and immune related proteins in HPV-positive and HPV-negative TSCC\/BOTSCC in relation to normal tissue, presence of HPV, and clinical outcome. Fresh frozen tissue from 42 HPV-positive and 17 HPV-negative TSCC\/BOTSCC, and corresponding normal samples, were analyzed for expression of 167 proteins using two Olink multiplex immunoassays. Major differences in protein expression between TSCC\/BOTSCC and normal tissue were identified, especially in chemo- and cytokines. Moreover, 34 proteins, mainly immunoregulatory proteins and chemokines, were differently expressed in HPV-positive vs HPV-negative TSCC\/BOTSCC. Several proteins were potentially related to clinical outcome for HPV-positive or HPV-negative tumors. For HPV-positive tumors, these were mostly related to angiogenesis and hypoxia. Correlation with clinical outcome of one of these, VEGFA, was validated by immunohistochemistry. Differences in immune related proteins between HPV-positive and HPV-negative TSCC\/BOTSCC reflect the stronger activity of the immune defense in the former. Angiogenesis related proteins might serve as potential targets for therapy in HPV-positive TSCC\/BOTSCC.<\/jats:p>","DOI":"10.3390\/ijms19040978","type":"journal-article","created":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T03:43:29Z","timestamp":1522035809000},"page":"978","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Protein Expression in Tonsillar and Base of Tongue Cancer and in Relation to Human Papillomavirus (HPV) and Clinical Outcome"],"prefix":"10.3390","volume":"19","author":[{"given":"Torbj\u00f6rn","family":"Ramqvist","sequence":"first","affiliation":[{"name":"Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4602-4297","authenticated-orcid":false,"given":"Anders","family":"N\u00e4sman","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Franz\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinzia","family":"Bersani","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8812-6481","authenticated-orcid":false,"given":"Andrey","family":"Alexeyenko","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, 171 77 Stockholm, Sweden"},{"name":"National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, 17121 Solna, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Becker","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linnea","family":"Haeggblom","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aeneas","family":"Kolev","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Dalianis","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Munck-Wikland","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pvr.2017.05.002","article-title":"Time to change perspectives on hpv in oropharyngeal cancer. 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