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

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.

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.

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.

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.