Smoking and oral and pharyngeal cancer: a meta-analysis

Introduction: Oral cavity and pharyngeal cancer (OPC) affects over 580,000 people globally each year, with tobacco and alcohol being key risk factors. This meta-analysis quantifies the excess risk of OPC associated with cigarette smoking and its patterns. Methods: We carried out a systematic review and meta-analysis of case-control and cohort studies assessing the association between cigarette smoking and OPC risk, including articles published up to February 2025. Using a combined umbrella and traditional review approach, we estimated pooled relative risks (RR) by smoking status, intensity, duration, and time since quitting. Results: Out of 137 eligible articles, 115 original studies were included in this meta-analysis. Relative to never smokers, the pooled risk of OPC was 3.58 (95% CI: 3.03–4.24; n = 54) among current smokers, 1.61 (95% CI: 1.44–1.81; n = 53) among former smokers, and 2.45 (95% CI: 2.19–2.75; n = 80) among ever smokers. Subsite-specific analyses showed RRs of 3.39 (95% CI: 2.64–4.35; n = 25) for oral cancer and 4.24 (95% CI: 2.96–6.09; n = 18) for pharyngeal cancer in current versus never smokers. Risk rose steeply with both smoking intensity and duration, doubling after 6 cigarettes per day or 7 years of smoking, before reaching a plateau around an RR of 5 at 20 cigarettes per day or 20 years. The risk declined linearly with longer time since quitting, with a 50% reduction observed within 10 years of cessation. Conclusion: Our findings reaffirm the substantial impact of smoking on OPC risk and stress the need for efforts to avoid smoking initiation and support cessation.