{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:28:20Z","timestamp":1762079300949,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T00:00:00Z","timestamp":1670284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Research Foundation","award":["TRR295","KFO339"],"award-info":[{"award-number":["TRR295","KFO339"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Recurrent aphthous stomatitis (RAS) is found among the most frequent diseases of the oral cavity. It is characterized by repeated formation of painful ulcers. The question has risen if due to potential tumor-promoting inflammation and sustaining proliferative signaling RAS may contribute to oral cancer. Accordingly, the aim of the study was to assess if an association of RAS and the development oral squamous cell carcinoma (OSCC) could be found in a larger cohort. As recurrent aphthous stomatitis is not classified as an oral potentially malignant disorder, it was assumed that the risk of OSCC did not differ between patients with (cohort I) and without RAS (cohort II). Methods: Retrospective clinical data of patients diagnosed with and without RAS (International Classification of Diseases (ICD)-10 code K12) within the past 20 years and a body mass index of 19\u201330 kg\/m2 were retrieved from the TriNetX database to gain initial cohort 0. Subjects suffering from RAS were assigned to cohort I, whereby cohort II was obtained from the remaining individuals, and by matching for age, gender, as well as (history of) nicotine and alcohol dependence. After defining the primary outcome as \u201cOSCC\u201d (ICD-10 codes C00-C14), a Kaplan\u2013Meier analysis was performed, and risk and odds ratios were calculated. Results: Of a total of 24,550,479 individuals in cohort 0, 72,845 subjects were each assigned to cohort I (females: 44,031 (60.44%); males: 28,814 (39.56%); mean current age (\u00b1standard deviation) = 35.51 \u00b1 23.55 years) and II (females: 44,032 (60.45%); males: 28,813 (39.55%); mean current age (\u00b1standard deviation) = 35.51 \u00b1 23.56 years). Among the cohorts I and II, 470 and 135 patients were diagnosed with OSCC within five years. The according risk of developing oral cancer was 0.65% and 0.18%, whereby the risk difference of 0.47% was highly significant (p &lt; 0.0001; Log-Rank test). The RR and OR were calculated as 3.48 (95% confidence interval (CI) lower: 2.88 and upper: 4.21) and 3.50 (95% CI lower: 2.89 and upper: 4.24). Conclusions: Among the patients suffering from RAS, a significantly augmented risk of developing OSCC was found. However, it has to be emphasized that the recent literature does not provide any confirmatory evidence that supports the retrieved results. Furthermore, the findings need to be interpreted cautiously due to specific limitations that come along with the applied methods. It should thus far only be concluded that further research is necessary to evaluate hypotheses that may be retrieved from the obtained results. Despite this controversy, oral ulcers suspicious of OSCC should undergo biopsy. Trial Registration: Due to the retrospective nature of the study, no registration was necessary.<\/jats:p>","DOI":"10.3390\/cancers14236011","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T04:00:37Z","timestamp":1670385637000},"page":"6011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Analysis of the Risk of Oral Squamous Cell Carcinoma in Patients with and without Recurrent Aphthous Stomatitis: A Retrospective Evaluation of Real-World Data of about 150,000 Patients"],"prefix":"10.3390","volume":"14","author":[{"given":"Moritz","family":"Hertel","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Senem","family":"Birinci","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4987-2913","authenticated-orcid":false,"given":"Max","family":"Heiland","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2407-1087","authenticated-orcid":false,"given":"Robert","family":"Preissner","sequence":"additional","affiliation":[{"name":"Institute of Physiology and Science-IT, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Philippstr. 12, 10115 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Nahles","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea-Maria","family":"Schmidt-Westhausen","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Oral Medicine and Oral Surgery, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, A\u00dfmannshauser Str. 4\u20136, 14197 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3672-0283","authenticated-orcid":false,"given":"Saskia","family":"Preissner","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,6]]},"reference":[{"key":"ref_1","first-page":"11884","article-title":"Essentials of oral cancer","volume":"8","author":"Rivera","year":"2015","journal-title":"Int. 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