Diabetes is associated with elevated mortality, stroke, and osteoradionecrosis in squamous cell carcinomas of the head and neck: a systematic review and meta-analysis

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Abstract Background Diabetes mellitus has been associated with an increased incidence and potentially with a worse prognosis of squamous cell carcinomas due to chronic inflammation, oxidative stress, and metabolic reprogramming, which promote tumor growth and therapy resistance. Furthermore, it impairs immune response and posttreatment healing, potentially leading to higher complication rates. Methods The study protocol was preregistered (CRD42025634653). An electronic search was conducted in MEDLINE, Embase, and Cochrane. Studies on patients with squamous cell carcinomas were included to compare survival metrics and complication rates with and without diabetes. Hazard ratios, odds ratios, and mean differences were extracted. A random-effects model was used, with subgroups based on cancer location. Results 63 predominantly retrospective studies met the inclusion criteria, with a population of 138,000 individuals. The meta-analysis found statistically significant differences in disease-specific (HR = 1.47 [1.11–1.96]; I 2 = 60%), overall (HR = 1.31 [1.23–1.39]; I 2 = 4%), and disease-free survival (HR = 1.58 [1.12–2.24]; I 2 = 58%); the subgroup analysis revealed that diabetes significantly affected oral and oropharyngeal subsites. Posttreatment stroke (HR = 2.11 [1.15–3.87]; I 2 = 70%) and osteoradionecrosis rates (HR = 2.2 [1.38–3.53]; I 2 = 11%) were significantly elevated. Conclusion Diabetes is associated with worse disease-specific survival in oral and oropharyngeal subtypes and a twofold higher risk of osteoradionecrosis development in patients with squamous cell carcinoma. Weaker evidence suggests that overall survival and stroke development rate are also affected by diabetes mellitus.

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