{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T09:27:14Z","timestamp":1767864434801,"version":"3.49.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Oral leukoplakia is one of the most frequent oral potentially malignant disorders. The present study aims to compare serum vitamin D levels between patients with and without oral leukoplakia, by smoking habit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This cross-sectional study involved a group of 45 cases with oral leukoplakia and a control group with 45 individuals. In both groups a pathology report was done, and for leukoplakia a binary classification of low- and high-grade epithelial dysplasia was employed. Serum 25(OH)D3 vitamin D levels, and data on smoking status, age, gender, comorbidities, and clinical and pathological characteristics were collected for both groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>vitamin D levels were lower in the oral leukoplakia group with a median of 19.1 ng\/ml, while the control group had a median of 24.8 ng\/ml. When subdividing each group by smoking habit, the smoking case group had a median of 19.4 ng\/ml (IQR: 15.7-21.5 ng\/ml), the non-smoking case group had 18.8 ng\/ml (IQR: 13.6-29.2 ng\/ml), the smoking control group had 21.8 ng\/ml (IQR: 17.5-27.3 ng\/ml), and the non-smoking control group had 25.4 ng\/ml (IQR: 20.4-32.9 ng\/ml) (p&amp;lt;0.05). When comparing serum vitamin D levels, statistically significant differences were found between the smoking case group versus the non-smoking control group and between the non-smoking case group versus the non-smoking control group (p&amp;lt;0.05). Serum vitamin D levels by histopathological diagnosis showed no differences between leukoplakia groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study shows that serum vitamin D levels were lower in patients with OL compared to those without OL, which was more evident in the smoking group. Patients with OL were previously observed to have hypovitaminosis D, without assessing smoking habits. This finding suggests a possible role of vitamin D deficiency in the development of OL, which could be more marked in smokers. This opens the possibility of future research on vitamin D as a chemopreventive agent in the malignant transformation of OL, and to evaluate the relationship between smoking and hypovitaminosis D.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1522726","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T07:10:17Z","timestamp":1738825817000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Hypovitaminosis D in patients with oral leukoplakia: insights from a cross-sectional study"],"prefix":"10.3389","volume":"15","author":[{"given":"Andrea","family":"Maturana-Ramirez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Aitken-Saavedra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dante","family":"Mora-Ferraro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Rojas-Zu\u0301n\u0303iga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris","family":"Espinoza-Santander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gonzalo","family":"Rojas-Alcayaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Ortega-Pinto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Montserrat","family":"Reyes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Lazo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Egardo","family":"Caaman\u00e3o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"B1","article-title":"WHO classification of head and neck tumours","author":"El-Naggar","year":"2017"},{"key":"B2","article-title":"Prognostic factors of survival rate in oral squamous cell carcinoma: clinical, histologic, genetic and molecular concepts","volume":"18","author":"Taghavi","year":"2015","journal-title":"Arch Iran Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/s41368-023-00249-w","article-title":"Oral squamous cell carcinomas: state of the field and emerging directions","volume":"15","author":"Tan","year":"2023","journal-title":"Int J Oral Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4317\/medoral.20368","article-title":"Serum vitamin D levels of patients with oral squamous cell carcinoma (OSCC) and expression of vitamin D receptor in oral precancerous lesions and OSCC","volume":"20","author":"Grimm","year":"2015","journal-title":"Med Oral Patol Oral Cirugia Bucal"},{"key":"B5","doi-asserted-by":"publisher","first-page":"23","DOI":"10.4103\/jpbs.JPBS_109_17","article-title":"Oral field cancerization and its clinical implications in the management in potentially Malignant disorders","volume":"9","author":"Sathiasekar","year":"2017","journal-title":"J Pharm Bioallied Sci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13704","article-title":"Oral potentially Malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer","volume":"27","author":"Warnakulasuriya","year":"2021","journal-title":"Oral Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13810","article-title":"Malignant transformation of oral leukoplakia: Systematic review and meta-analysis of the last 5 years","volume":"27","author":"Aguirre-Urizar","year":"2021","journal-title":"Oral Dis"},{"key":"B8","first-page":"1 p","volume-title":"Head and Neck Tumours: Who Classification of Tumours","year":"2022"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/odi.1383","article-title":"Malignant transformation of oral proliferative verrucous leukoplakia: A systematic review and meta-analysis","volume":"27","author":"Ramos-Garc\u00eda","year":"2021","journal-title":"Oral Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3691","article-title":"The role of vitamin D in reducing cancer risk and progression","volume":"14","author":"Feldman","year":"2014","journal-title":"Nat Rev Cancer"},{"key":"B12","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.biopha.2018.10.102","article-title":"Role of vitamin D and vitamin D receptor (VDR) in oral cancer","volume":"109","author":"Fathi","year":"2019","journal-title":"BioMed Pharmacother"},{"key":"B13","doi-asserted-by":"publisher","first-page":"36017","DOI":"10.1038\/srep36017","article-title":"Circulating vitamin D in relation to cancer incidence and survival of the head and neck and oesophagus in the EPIC cohort","volume":"6","author":"Fanidi","year":"2016","journal-title":"Sci Rep"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/cre2.v6.4","article-title":"Serum levels of 25-hydroxy-vitamin D in patients with oral squamous cell carcinoma: Making a case for chemoprevention","volume":"6","author":"Udeabor","year":"2020","journal-title":"Clin Exp Dent Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3109\/19390211.2013.859209","article-title":"Differential effects of 1,25-dihydroxyvitamin D3 on oral squamous cell carcinomas in vitro","volume":"11","author":"Osafi","year":"2014","journal-title":"J Diet Suppl"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD001829.pub4","article-title":"Interventions for treating oral leukoplakia to prevent oral cancer","volume":"7","author":"Lodi","year":"2016","journal-title":"Cochrane Database Syst Rev"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2010.04.008","article-title":"Use of \u03b1,25-Dihydroxyvitamin D3 treatment to stimulate immune infiltration into head and neck squamous cell carcinoma","volume":"71","author":"Walsh","year":"2010","journal-title":"Hum Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00099-11","article-title":"Vitamin D-mediated induction of innate immunity in gingival epithelial cells","volume":"79","author":"McMahon","year":"2011","journal-title":"B\u00e4umler AJ editor. Infect Immun"},{"key":"B19","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.jobcr.2023.11.005","article-title":"Assessment of vitamin D levels in patients with oral potentially Malignant disorders and oral squamous cell carcinoma-A cross-sectional study","volume":"14","author":"Samanta","year":"2024","journal-title":"J Oral Biol Craniofacial Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1177\/00220345221092751","article-title":"Areca nut and oral cancer: evidence from studies conducted in humans","volume":"101","author":"Warnakulasuriya","year":"2022","journal-title":"J Dent Res"},{"key":"B21","article-title":"The Helsinki Declaration at 50 years: comments on the 2013 modifications","volume":"24","author":"Domj\u00e1n","year":"2014","journal-title":"Lege Artis Med Uj Magy Orvosi Hirmondo"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2188\/jea.17.125","article-title":"Relationship between smoking status and tooth loss: Findings from national databases in Japan","volume":"17","author":"Hanioka","year":"2007","journal-title":"J Epidemiol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(85)90133-X","article-title":"Importance of total life consumption of cigarettes as a risk factor for coronary artery disease","volume":"55","author":"Weintraub","year":"1985","journal-title":"Am J Cardiol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1037\/pha0000258","article-title":"Pack-years of tobacco cigarette smoking as a predictor of spontaneous pain reporting and experimental pain reactivity","volume":"27","author":"De Vita","year":"2019","journal-title":"Exp Clin Psychopharmacol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5935\/2525-5711.20170029","article-title":"Frequency and histoclinic pathology of Malignant and potentially Malignant disorders of oral cavity in Chile","volume":"2","author":"Aitken-Saavedra","year":"2017","journal-title":"JORDI - J Oral Diagn"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/jop.2018.47.issue-7","article-title":"Prevalence of oral potentially Malignant disorders: A systematic review and meta-analysis","volume":"47","author":"Mello","year":"2018","journal-title":"J Oral Pathol Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2013-003320","article-title":"Do men consult less than women? An analysis of routinely collected UK general practice data","volume":"3","author":"Wang","year":"2013","journal-title":"BMJ Open"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djz238","article-title":"Oral leukoplakia and risk of progression to oral cancer: A population-based cohort study","volume":"112","author":"Chaturvedi","year":"2020","journal-title":"JNCI J Natl Cancer Inst"},{"key":"B29","unstructured":"Informe Encuesta Nacional de Salud 2016-2017: Hipertensi\u00f3n arterial\n          \n          \n          \n          2018"},{"key":"B30","unstructured":"Informe Encuesta Nacional de Salud 2016-2017: Diabetes Mellitus\n          \n          \n          \n          2018"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.829307","article-title":"Serum vitamin D levels in relation to hypertension and pre-hypertension in adults: A systematic review and dose\u2013response meta-analysis of epidemiologic studies","volume":"9","author":"Mokhtari","year":"2022","journal-title":"Front Nutr"},{"key":"B32","doi-asserted-by":"publisher","first-page":"15485","DOI":"10.3390\/ijms242015485","article-title":"The role of vitamin D and its molecular bases in insulin resistance, diabetes, metabolic syndrome, and cardiovascular disease: state of the art","volume":"24","author":"Argano","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B33","unstructured":"Informe Encuesta Nacional de Salud 2016-2017: Consumo de tabaco\n          \n          \n          \n          2018"},{"key":"B34","doi-asserted-by":"publisher","first-page":"5232","DOI":"10.1038\/s41598-024-54410-4","article-title":"Prevalence and risk factors of oral potentially Malignant disorders in Indonesia: a cross-sectional study undertaken in 5 provinces","volume":"14","author":"Sari","year":"2024","journal-title":"Sci Rep"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.v9.10","article-title":"Smoking behavior and circulating vitamin D levels in adults: A meta-analysis","volume":"9","author":"Yang","year":"2021","journal-title":"Food Sci Nutr"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2012.201939","article-title":"Low plasma 25-hydroxyvitamin D and risk of tobacco-related cancer","volume":"59","author":"Afzal","year":"2013","journal-title":"Clin Chem"},{"key":"B37","unstructured":"Informe Encuesta Nacional de Salud 2016-2017: Vitamina D\n          \n          \n          \n          2018"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1093\/nutrit\/nuad010","article-title":"Prevalence of vitamin D deficiency in South America: a systematic review and meta-analysis","volume":"81","author":"Mendes","year":"2023","journal-title":"Nutr Rev"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.4067\/S0034-98872016000600011","article-title":"C\u00e1ncer oral en Chile: Revisi\u00f3n de la literatura","volume":"144","author":"Santelices Ch","year":"2016","journal-title":"Rev M\u00e9dica Chile"},{"key":"B40","doi-asserted-by":"publisher","first-page":"18355","DOI":"10.1038\/s41598-023-45862-1","article-title":"Social determinants of serum 25-hydroxyvitamin D concentrations deficiency in older Chilean people","volume":"13","author":"Alvear-Vega","year":"2023","journal-title":"Sci Rep"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2014.2338","article-title":"Vitamin D signaling regulates oral keratinocyte proliferation in vitro and in vivo","volume":"44","author":"Yuan","year":"2014","journal-title":"Int J Oncol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3390\/cimb46040191","article-title":"Calcitriol treatment decreases cell migration, viability and \u03b2-catenin signaling in oral dysplasia","volume":"46","author":"Pe\u00f1a-Oyarz\u00fan","year":"2024","journal-title":"Curr Issues Mol Biol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.5114\/wo.2017.68623","article-title":"Expression of vitamin D receptor and vitamin D status in patients with oral neoplasms and effect of vitamin D supplementation on quality of life in advanced cancer treatment","volume":"2","author":"Anand","year":"2017","journal-title":"Wsp\u00f3\u0142czesna Onkol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.4317\/medoral.25049","article-title":"Hypovitaminosis D, oral potentially Malignant disorders, and oral squamous cell carcinoma: a systematic review","volume":"27","author":"Maturana-Ram\u00edrez","year":"2022","journal-title":"Med Oral Patol Oral Cirugia Bucal"},{"key":"B45","article-title":"Expression of immunohistochemical markers of progression in pre-cancerous and cancerous human colon: correlation with serum vitamin D levels","volume":"35","author":"Juniku-Shkololli","year":"2015","journal-title":"Anticancer Res"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-018-0038-9","article-title":"Exploring vitamin D metabolism and function in cancer","volume":"50","author":"Jeon","year":"2018","journal-title":"Exp Mol Med"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.3390\/nu14071448","article-title":"Vitamin D and cancer: an historical overview of the epidemiology and mechanisms","volume":"14","author":"Mu\u00f1oz","year":"2022","journal-title":"Nutrients"},{"key":"B48","doi-asserted-by":"publisher","first-page":"2346","DOI":"10.3390\/nu15102346","article-title":"Vitamin D in the prevention and treatment of oral cancer: A scoping review","volume":"15","author":"Hung","year":"2023","journal-title":"Nutrients"},{"key":"B49","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-030-46227-7_15","article-title":"Crosstalk between vitamin D and p53 signaling in cancer: an update","volume-title":"Sunlight, Vitamin D and Skin Cancer","author":"Reichrath","year":"2020"},{"key":"B50","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s13052-019-0634-x","article-title":"Vitamin D inhibits pro-inflammatory cytokines in the airways of cystic fibrosis patients infected by Pseudomonas aeruginosa- pilot study","volume":"45","author":"Olszowiec-Chlebna","year":"2019","journal-title":"Ital J Pediatr"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnae009","article-title":"Consensus statement on vitamin D status assessment and supplementation: whys, whens, and hows","volume":"45","author":"Giustina","year":"2024","journal-title":"Endocr Rev"},{"key":"B52","unstructured":"Gu\u00eda de buena pr\u00e1ctica cl\u00ednica en geriatr\u00eda: Vitamina D en adulto mayor\n          \n          \n          \n          2023"},{"key":"B53","doi-asserted-by":"publisher","first-page":"104550","DOI":"10.1016\/j.oraloncology.2019.104550","article-title":"Oral potentially Malignant disorders: A comprehensive review on clinical aspects and management","volume":"102","author":"Warnakulasuriya","year":"2020","journal-title":"Oral Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1522726\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T07:10:24Z","timestamp":1738825824000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1522726\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,6]]},"references-count":53,"alternative-id":["10.3389\/fonc.2025.1522726"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1522726","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,6]]},"article-number":"1522726"}}