{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:41:13Z","timestamp":1791841273935,"version":"4.3.4"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The aim of this study was to investigate the clinical, histopathologic, and immunologic differences of oral squamous cell carcinoma of never-smokers\/never-drinkers and smokers\/drinkers. Immunohistochemical staining for CD4, CD8, FoxP3, CD1a, and p16 was performed in 131 oral squamous cell carcinomas from smokers\/drinkers and never-smokers\/never-drinkers. Associations of smoking\/drinking status with clinicopathologic data, immunohistochemical antibody expression, and survival were examined. Oral squamous cell carcinoma in never-smokers\/never-drinkers was associated with the female gender (p &lt; 0.001). Never-smokers\/never-drinkers were older at diagnosis than smokers\/drinkers (p &lt; 0.001). Never-smokers\/never-drinkers had more tumors in the maxilla, mandible, and tongue (p &lt; 0.001). Pre-existing oral potentially malignant disorders appeared to be more common in never-smokers\/never-drinkers (p &lt; 0.001). Perineural invasion was more common in smokers\/drinkers (p = 0.039). Never-smoking\/never-drinking was associated with better overall survival (p = 0.004) and disease-specific survival (p = 0.029). High CD4+ T cell infiltration was associated with never-smoking\/never-drinking (p = 0.008). Never-smokers\/never-drinkers also showed increased CD8+ T cell infiltration (p = 0.001) and increased FoxP3+ Treg infiltration (p = 0.023). Furthermore, the total group of tumor-infiltrating lymphocytes was associated with never smoking\/never drinking (p = 0.005). To conclude oral squamous cell carcinoma of the never-smokers\/never-drinkers appears to be a distinct type of tumor, as it appears to have unique clinical and pathologic features and a more immunogenic microenvironment.<\/jats:p>","DOI":"10.3390\/cancers15102688","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T03:49:06Z","timestamp":1683690546000},"page":"2688","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["OSCC in Never-Smokers and Never-Drinkers Is Associated with Increased Expression of Tumor-Infiltrating Lymphocytes and Better Survival"],"prefix":"10.3390","volume":"15","author":[{"given":"Mathias","family":"Fiedler","sequence":"first","affiliation":[{"name":"Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strau\u00df-Allee 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa","family":"Off","sequence":"additional","affiliation":[{"name":"Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strau\u00df-Allee 11, 93053 Regensburg, Germany"},{"name":"Insitute of Pathology, University of Regensburg, Franz-Josef-Strau\u00df-Allee 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Eichberger","sequence":"additional","affiliation":[{"name":"Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strau\u00df-Allee 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Spoerl","sequence":"additional","affiliation":[{"name":"Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strau\u00df-Allee 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3973-2474","authenticated-orcid":false,"given":"Johannes G.","family":"Schuderer","sequence":"additional","affiliation":[{"name":"Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strau\u00df-Allee 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9733-3703","authenticated-orcid":false,"given":"Juergen","family":"Taxis","sequence":"additional","affiliation":[{"name":"Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strau\u00df-Allee 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strau\u00df-Allee 11, 93053 Regensburg, Germany"},{"name":"Department of Cranio- and Maxillofacial Surgery, Center for Medical Biotechnology, Hospital of the University of Regensburg, Franz-Josef-Strau\u00df-Allee 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2820-1942","authenticated-orcid":false,"given":"Stephan","family":"Schreml","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hospital of the University of Regensburg, Franz-Josef-Strau\u00df-Allee 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten E.","family":"Reichert","sequence":"additional","affiliation":[{"name":"Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strau\u00df-Allee 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Ettl","sequence":"additional","affiliation":[{"name":"Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strau\u00df-Allee 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7480-8828","authenticated-orcid":false,"given":"Florian","family":"Weber","sequence":"additional","affiliation":[{"name":"Insitute of Pathology, University of Regensburg, Franz-Josef-Strau\u00df-Allee 11, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1159\/000446117","article-title":"Global Epidemiology of Head and Neck Cancers: A Continuing 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