Opium Use and the Risk of Head and Neck Squamous Cell Carcinoma.

Scant evidence exists to support the association of opium use with head and neck cancer, limited to the larynx and oral cavity. In a multicenter case-control study -Iran Opium and Cancer study (IROPICAN), we recruited 633 cases of head and neck squamous cell carcinoma (HNSCC) (254 lip and oral cavity, 54 pharynx, 327 larynx, and 28 other sub-sites within the head and neck) and 3065 frequency-matched controls from April 2016 to April 2019. Odds ratios (ORs) for opium use and 95% confidence intervals (95% CIs) were obtained using mixed-effects logistic regression because of heterogeneity amongst centers. The adjusted OR (95% CI) for regular opium use was 3.76 (2.96 to 4.79) for all HNSCC combined. Strong dose-response effects were observed by frequency or amount of use, and duration of use. Regular opium uses significantly increased the risk of HNSCC of the pharynx, larynx, and other sub-sites within the head and neck with OR (95% CI) of 2.90 (1.40 to 6.02), 6.55 (4.69 to 9.13), and 5.95 (2.41 to 14.71), respectively. The observed associations were significant even among never tobacco smokers (including cigarette and water-pipe smoking). Moreover, by the multiplicative interaction scale, the effect of opium use could be varied by cigarette smoking on HNSCC, 8.16 (6.20 to 10.74). For the first time, the current study showed opium users have an increased risk of several anatomic sub-sites of HNSCC.