{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T17:47:47Z","timestamp":1763142467293,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oral"],"abstract":"<jats:p>Background\/Objectives: Emerging evidence links diabetes to increased cancer risk. This study aimed to assess the association between diabetes mellitus (DM)(type 1, type 2, or gestational) and the development of head and neck cancer. Methods: An umbrella review was conducted using systematic searches in Cochrane, EBSCO, Wiley, ScienceDirect, and PubMed (January 2000\u2013January 2024), registered in PROSPERO (CRD42024512151). Included were systematic reviews (SRs) and meta-analyses (MAs) of observational studies. Article selection followed the PRISMA guidelines; the quality and risk of bias of the selected studies were assessed with the Joanna Briggs Institute Checklist. The GROOVE tool was used to identify double counting. Two independent reviewers screened studies, with a third resolving disagreements. Results: Seven SRs were included. While DM has been widely examined in cancer research, few studies specifically targeted head and neck cancers. Of the 20 associations between various cancer sites and diabetes types, 9 (45%) showed a statistically significant positive correlation. The strongest evidence was for overall cancer risk (RR = 1.22, 95% CI: 1.16\u20131.29, p &lt; 0.001). Oral cancer showed elevated risks (RRR = 1.13, p = 0.009; OR = 1.32, p &lt; 0.001; HR = 1.73, p &lt; 0.05; RR = 1.28, p &lt; 0.05). Increased risks were also observed for oropharyngeal (RR = 1.18; HR = 1.53), head and neck (HR = 1.47), and nasopharyngeal cancer (OR = 1.40), all p &lt; 0.05. Heterogeneity was low in two reviews, unreported in one, and high in four. Five SRs reported associated risk factors. Conclusions: While some associations between DM and cancer appear significant, evidence remains limited and inconsistent, particularly for oral cancer. Further standardized, high-quality research is needed to clarify the link across head and neck cancer subtypes.<\/jats:p>","DOI":"10.3390\/oral5030052","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T15:19:22Z","timestamp":1753370362000},"page":"52","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association Between Diabetes Mellitus and Head and Neck Cancer: An Umbrella Review of Systematic Reviews and Meta-Analyses"],"prefix":"10.3390","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6893-5757","authenticated-orcid":false,"given":"Filipa","family":"Formosinho","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences, University Fernando Pessoa, 4249-004 Porto, Portugal"}]},{"given":"Alexandra","family":"Arcanjo","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University Fernando Pessoa, 4249-004 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1774-1337","authenticated-orcid":false,"given":"Maria Concei\u00e7\u00e3o","family":"Manso","sequence":"additional","affiliation":[{"name":"RISE-Health, FP-I3ID, FP-BHS, Faculty of Health Sciences, Fernando Pessoa University, Fernando Pessoa Teaching and Culture Foundation, Rua Carlos da Maia, 296, 4200-150 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13005-021-00286-y","article-title":"Biological consequences of cancer radiotherapy in the context of oral squamous cell carcinoma","volume":"17","author":"Feller","year":"2021","journal-title":"Head Face Med."},{"key":"ref_2","unstructured":"Mouth Cancer Foundation (2024, February 23). Symptoms. Available online: https:\/\/www.mouthcancerfoundation.org\/symptoms\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/s40001-022-00835-4","article-title":"Tumor microenvironment and immunotherapy of oral cancer","volume":"27","author":"Liu","year":"2022","journal-title":"Eur. J. Med. Res."},{"key":"ref_4","unstructured":"National Health System (2024, February 23). Mouth Cancer\u2014Treatment. Available online: https:\/\/www.nhs.uk\/conditions\/mouth-cancer\/treatment\/."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s10147-014-0689-z","article-title":"Current status of oral cancer treatment strategies: Surgical treatments for oral squamous cell carcinoma","volume":"19","author":"Omura","year":"2014","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s10555-017-9690-0","article-title":"Alcohol and head and neck cancer","volume":"36","author":"Kawakita","year":"2017","journal-title":"Cancer Metastasis Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1053\/j.seminoncol.2019.07.002","article-title":"Modern radiotherapy for head and neck cancer","volume":"46","author":"Alterio","year":"2019","journal-title":"Semin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2010). Diagnosis and Classification of Diabetes Mellitus. Diabetes Care, 34, S62\u2013S69.","DOI":"10.2337\/dc11-S062"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.arcmed.2005.01.003","article-title":"Pathogenesis of Type 2 Diabetes Mellitus","volume":"36","author":"Leahy","year":"2005","journal-title":"Arch. Med. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41574-022-00690-7","article-title":"The Burden and Risks of Emerging Complications of Diabetes Mellitus","volume":"18","author":"Tomic","year":"2022","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"14635","DOI":"10.1074\/jbc.M608565200","article-title":"Glucose Modulates Basement Membrane Fibroblast Growth Factor-2 via Alterations in Endothelial Cell Permeability","volume":"282","author":"Morss","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/ncponc0062","article-title":"Therapy insight: Influence of type 2 diabetes on the development, treatment and outcomes of cancer","volume":"2","author":"Richardson","year":"2005","journal-title":"Nat. Clin. Pract. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.jdiacomp.2010.06.004","article-title":"Substantially increased risk of cancer in patients with diabetes mellitus","volume":"24","author":"Noto","year":"2010","journal-title":"J. Diabetes Its Complicat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.oraloncology.2015.01.003","article-title":"Type 2 diabetes mellitus and risk of oral cancer and precancerous lesions: A meta-analysis of observational studies","volume":"51","author":"Gong","year":"2015","journal-title":"Oral Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"n160","DOI":"10.1136\/bmj.n160","article-title":"PRISMA 2020 explanation and elaboration: Updated guidance and exemplars for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1097\/XEB.0000000000000055","article-title":"Summarizing systematic reviews: Methodological development, conduct and reporting of an umbrella review approach","volume":"13","author":"Aromataris","year":"2015","journal-title":"Int. J. Evid.-Based Healthc."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Aromataris, E., and Munn, Z. (2020). JBI Reviewer\u2019s Manual, JBI.","DOI":"10.46658\/JBIRM-20-02"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1093\/jjco\/hyy047","article-title":"Type 1 diabetes mellitus and risk of cancer: A meta-analysis of observational studies","volume":"48","author":"Sona","year":"2018","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1007\/s00125-018-4664-5","article-title":"Sex differences in the association between diabetes and cancer: A systematic review and meta-analysis of 121 cohorts including 20 million individuals and one million events","volume":"61","author":"Ohkuma","year":"2018","journal-title":"Diabetologia"},{"key":"ref_20","first-page":"404","article-title":"Diabetes mellitus and oral cancer\/oral potentially malignant disorders: A systematic review and meta-analysis","volume":"27","year":"2020","journal-title":"Oral Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00592-020-01643-0","article-title":"Type 2 diabetes mellitus and risk of head and neck cancer subtypes: A systematic review and meta-analysis of observational studies","volume":"58","author":"Yan","year":"2021","journal-title":"Acta Diabetol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1002\/hed.27193","article-title":"Systemic conditions associated with increased risk to develop oral squamous cell carcinoma: Systematic review and meta-analysis","volume":"44","author":"Normando","year":"2022","journal-title":"Head Neck"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e058392","DOI":"10.1136\/bmjopen-2021-058392","article-title":"Metabolic disorders and the risk of head and neck cancer: A protocol for a systematic review and meta-analysis","volume":"12","author":"Gormley","year":"2022","journal-title":"BMJ Open"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.3390\/ijms20122940","article-title":"Oral Submucous Fibrosis: A Review on Etiopathogenesis, Diagnosis, and Therapy","volume":"20","author":"Shih","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1093\/ajcn\/87.3.627","article-title":"Glycemic index, glycemic load, and chronic disease risk\u2014A meta-analysis of observational studies","volume":"87","author":"Barclay","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3569","DOI":"10.1128\/MCB.01447-06","article-title":"Differential Activation of Insulin Receptor Substrates 1 and 2 by Insulin-Like Growth Factor-Activated Insulin Receptors","volume":"27","author":"Denley","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S1470-2045(05)01736-5","article-title":"Diabetes mellitus and breast cancer","volume":"6","author":"Wolf","year":"2005","journal-title":"Lancet Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3109S","DOI":"10.1093\/jn\/131.11.3109S","article-title":"Insulin, insulin-like growth factors and colon cancer: A review of the evidence","volume":"131","author":"Giovannucci","year":"2001","journal-title":"J. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.2337\/dc10-0666","article-title":"Diabetes and Cancer: A consensus report","volume":"33","author":"Giovannucci","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/nrc2734","article-title":"STATs in cancer inflammation and immunity: A leading role for STAT3","volume":"9","author":"Yu","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/nrc1408","article-title":"Overweight, obesity and cancer: Epidemiological evidence and proposed mechanisms","volume":"4","author":"Calle","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_32","unstructured":"American Cancer Society (2024, March 20). Signs and Symptoms of Oral Cavity and Oropharyngeal Cancer. Available online: https:\/\/www.cancer.org\/cancer\/types\/oral-cavity-and-oropharyngeal-cancer\/causes-risks-prevention\/risk-factors.html."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0167-4889(02)00276-8","article-title":"Leptin and high glucose stimulate cell proliferation in MCF-7 human breast cancer cells: Reciprocal involvement of PKC-\u03b1 and PPAR expression","volume":"1592","author":"Okumura","year":"2002","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1001\/jama.2008.824","article-title":"Long-term All-Cause Mortality in Cancer Patients with Preexisting Diabetes Mellitus","volume":"300","author":"Barone","year":"2008","journal-title":"JAMA"}],"container-title":["Oral"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2673-6373\/5\/3\/52\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:15:41Z","timestamp":1760033741000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2673-6373\/5\/3\/52"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,24]]},"references-count":34,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["oral5030052"],"URL":"https:\/\/doi.org\/10.3390\/oral5030052","relation":{},"ISSN":["2673-6373"],"issn-type":[{"type":"electronic","value":"2673-6373"}],"subject":[],"published":{"date-parts":[[2025,7,24]]}}}