Risk of Head and Neck Cancer in Former Smokers by Subsite: A Multicenter Analysis From the INHANCE Consortium

This study investigated risk factors associated with HNC by subsite including oral cavity cancer (OCC), oropharyngeal cancer (OPC), and laryngeal cancer (LC) among former smokers in the International Head and Neck Cancer Epidemiology Consortium (INHANCE). Case-control study including former smokers from the pooled INHANCE data, with information on sociodemographic, smoking, and alcohol history. Associations were assessed using logistic regression with 95% confidence intervals (CI). The study included 2143 cases with HNC and 5799 controls. Cancer cases were categorized by their respective subsites: 954 LC (44.5%), 685 OPC (32.0%), 504 OCC (23.5%). The risk of developing OCC was 2.8-fold higher [CI: 1.9–4.1], LC 2.6-fold higher [CI: 1.9–3.5], and OPC 2.1-fold higher [CI: 1.5–2.8] in individuals who smoked > 50 pack-years, compared to < 10 pack-years. The risk of OCC/OPC/LC increased with tobacco consumption in North-America, whereas in Western/Southern-Europe and South-America the association plateaued beyond 31–50 pack-years. Cessation after age 55 increased the risk of LC by 3.0-fold [CI: 2.2–4.2], and OCC by 2.2-fold [CI: 1.4–3.3] versus cessation age ≤ 45 years. Consuming ≥ 5 drinks/day was associated with 5-fold higher risk of OPC [CI: 3.7–6.6], 4.4-fold higher risk of OCC [CI: 3.2–6.1] and 3.1-fold higher risk of LC [CI: 2.4–3.9] compared to 0–0.9 drinks/day. The risk of HNC among former smokers is not homogeneous across regions and that there were distinct patterns for OCC, OPC, and LC. The amount of tobacco and alcohol consumption are key risk factors, with alcohol being more important for OCC/OPC, and tobacco being more strongly associated with LC risk.