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In head and neck SCC, peripheral node addressin (PNAd)\u2009+\u2009tumour-associated high endothelial venules (TA-HEVs) and CD163+\u2009tumour-associated macrophages (TAMs) are associated with favourable and unfavourable prognoses, respectively, whereas the prognostic value of FoxP3+\u2009cells is controversial. This national, multi-centre retrospective study evaluates the prognostic roles of these biomarkers individually and in combination in a homogeneous cohort of 126 treatment-na\u00efve OTSCC patients diagnosed in Norway (2005\u20132009).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>Immunohistochemistry on formalin-fixed, paraffin-embedded tissue assessed PNAd+\u2009TA-HEVs, CD163+\u2009TAMs, and FoxP3+\u2009cell densities. Associations between scores and clinical\/pathological variables were analysed using chi-square tests. Five-year disease-specific death (DSD) prediction was evaluated using cumulative incidence function estimation and Fine-Gray subdistribution hazard modelling to account for competing mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In multivariable competing-risk analyses, high FoxP3\u207a cell density independently predicted increased five-year DSD (sHR\u2009=\u20095.40, 95% CI 1.92\u201315.17). PNAd demonstrated context-dependent prognostic effects when analysed with FoxP3: high PNAd\/low FoxP3 tumours showed excellent prognosis, whereas low PNAd\/high FoxP3 conferred highest risk (combined model: PNAd sHR 2.58, 95% CI 1.25\u20135.34; FoxP3 sHR 8.78, 95% CI 3.53\u201321.87). CD163\u207a TAM density was not associated with DSD. Combined biomarker assessment added incremental prognostic value beyond pTNM staging, with higher discrimination (C-index 0.727\u2009\u2192\u20090.784) and improved model fit (\u0394AICc\u2009=\u2009\u2009\u2212\u20098.93;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Higher FoxP3+\u2009cell density independently predicted increased DSD, while PNAd showed context-dependent prognostic value. Combined biomarker assessment improved risk stratification beyond pTNM staging, supporting investigation of integrated immune profiling for risk stratification, pending external validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12105-026-01904-4","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T11:26:09Z","timestamp":1774524369000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FoxP3+\u2009Cells and PNAd+\u2009Tumour-Associated High Endothelial Venules: Synergistic Prognostic Markers in Oral Tongue Squamous Cell Carcinoma"],"prefix":"10.1007","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9553-3355","authenticated-orcid":false,"given":"Ibrahim Afolabi","family":"Abdulsalam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjersti","family":"Sell\u00e6g","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faith O.","family":"Benebo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy C.","family":"Ojei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja E.","family":"Steigen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Uhlin-Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inger-Heidi","family":"Bjerkli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Wirsing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Synn\u00f8ve Norvoll","family":"Magnussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elin","family":"Hadler-Olsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"1904_CR1","doi-asserted-by":"publisher","first-page":"140","DOI":"10.14639\/0392-100X-N2055","volume":"42","author":"M Tagliabue","year":"2022","unstructured":"Tagliabue M, De Berardinis R, Belloni P, Gandini S, Scaglione D, Maffini F et al (2022) Oral tongue carcinoma: prognostic changes according to the updated 2020 version of the AJCC\/UICC TNM staging system. 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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of retrospective study, formal consent is not required; however, patients who were still alive were given the opportunity to opt out, and the requirement for written or oral informed consent was waived by the ethics committee.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"For this type of retrospective study using anonymised archival material, consent for publication is not required.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"This study obtained approval from Regional Committee for Medical and Health Research Ethics of Northern Norway, and the requirement for informed consent was waived for this retrospective study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}}],"article-number":"35"}}