Aspirin initiation and dose-dependent risk reduction of oral squamous cell carcinoma in areca nut chewers

BACKGROUND: Oral cavity squamous cell carcinoma (OCSCC) driven by areca nut consumption-a Group 1 carcinogen affecting 600 million people globally-represents a significant unmet need in precision prevention. Despite the known role of COX-2-mediated inflammation in this etiologic niche, pharmacological strategies remain under-evaluated. METHODS: We emulated a target trial using a nationwide matched cohort of 50,606 areca nut chewers from the Taiwan National Health Insurance Research Database (2008 to 2021). To minimize selection and immortal time biases, we utilized time-dependent exposure modeling and Fine-Gray subdistribution hazard models to account for competing mortality. RESULTS: Aspirin initiation was associated with a significantly lower risk of incident OCSCC (adjusted sHR, 0.75; 95% CI, 0.65-0.87; P