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Biomarkers have been beneficial in the management of other cancers, however, not in HNCs. Therefore, we observed the immunopositivity of a novel biomarker called immunoglobulin superfamily member 3 (IGSF3) in tumor tissues in HPV\u2010related and HPV\u2010unrelated OPSCC. Two patient cohorts (C1 and C2) from separate time periods were available for this study (total <jats:italic>N<\/jats:italic>\u2009=\u2009282). Both consisted of OPSCC patients treated at the Helsinki University Hospital (HUS, Helsinki, Finland) during 2000\u20132016. For HPV determination, HPV mRNA <jats:italic>in situ<\/jats:italic> hybridization was used. Immunohistochemistry was used to assess IGSF3 immunopositivity in cancer tissues. Overall survival (OS) was used as endpoint in the statistical analysis. In C1, stronger immunopositivity of IGSF3 in tumor\u2010infiltrating lymphocytes (TILs) correlated with favorable OS (p\u2009=\u20090.005). Stronger IGSF3 immunopositivity in tumor cells (TCs) was associated with HPV negativity (p\u2009=\u20090.017). Stronger IGSF3 immunopositivity in TILs correlated with HPV positivity (p\u2009&lt;\u20090.001). Elevated IGSF3 immunopositivity in TILs associates with HPV\u2010related tumors and may signify favorable prognosis. The immunopositivity of IGSF3 differs between HPV\u2010related and HPV\u2010unrelated OPSCC.<\/jats:p>","DOI":"10.1111\/apm.13417","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T07:35:21Z","timestamp":1713252921000},"page":"1061-1070","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>IGSF3<\/scp> tissue expression in squamous cell carcinoma of the oropharynx: a novel tool for prognosis assessment in <scp>HPV<\/scp>\u2010related and <scp>HPV<\/scp>\u2010unrelated disease"],"prefix":"10.1111","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1740-4346","authenticated-orcid":false,"given":"Anni","family":"Sj\u00f6blom","sequence":"first","affiliation":[{"name":"Department of Pathology University of Helsinki and Helsinki University Hospital  Helsinki Finland"},{"name":"Research Program in Systems Oncology, Faculty of Medicine University of Helsinki  Helsinki 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