Smoking, Alcohol, and Their Interaction in the Risk of Head and Neck Cancer: A Nationwide Cohort Study

BACKGROUND: Smoking and alcohol drinking are established causes of head and neck cancer (HNC), yet their combined effect and variation by anatomic sub-site remain incompletely defined. METHODS: We followed 5,985,244 Korean adults (≥ 30 years) who attended National Health Insurance health screening in 2002-2003 until 31 December 2019. Smoking status (never, former, current) and alcohol intake (none, light, moderate, heavy) were self-reported at baseline. Incident HNC was ascertained from the national cancer registry. Sub-distribution hazard ratios (SHRs) were estimated with Fine-Gray competing-risk regression. Additive interaction was quantified by the relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI), and multiplicative interaction by a product term. RESULTS: During 76.5 million person-years of follow-up (mean 13-year follow-up), 13,491 HNC cases were recorded. Current smoking and heavy alcohol drinking independently increased HNC risk in a dose-response manner. Combined exposure to smoking and heavy drinking showed a supra-additive risk for HNC overall (SHR, 2.42; 95% CI, 2.28-2.56; RERI, 0.63; AP, 0.26; SI, 1.79), particularly for the oral cavity, oropharynx, nasal cavity/paranasal sinuses, and larynx. Significant multiplicative interactions were also observed in the oral cavity, oropharynx, and hypopharynx. CONCLUSION: Concurrent cigarette smoking and heavy alcohol consumption synergistically elevate the risk of HNC across multiple subsites. Integrated public-health strategies targeting both behaviors are essential to reduce the HNC burden.