A large multicenter cohort study found that individuals diagnosed with cannabis use disorder had a significantly higher risk of developing head and neck cancers compared to those without the disorder. The study analyzed data from 64 U.S. health care organizations spanning 20 years through April 2024. The findings suggested that the association between cannabis use and head and neck cancer was independent of alcohol and tobacco use.
The study, published in JAMA Otolaryngology–Head & Neck Surgery, included a cohort of 116,076 individuals with cannabis use disorder and 3,985,286 individuals without the disorder, matched for demographic characteristics, alcohol-related disorders, and tobacco use. The data came from the TriNetX research network, which provided deidentified electronic medical records from over 90 million individuals. The index event was defined as the first recorded outpatient hospital clinic visit or the first time when both outpatient visit and cannabis use disorder diagnosis criteria were met. Propensity-score matching was used to create balanced cohorts, and Poisson regression analysis was employed to calculate risk ratios (RRs).
After propensity-score matching, individuals with cannabis use disorder had a 3.49 times higher risk (95% confidence interval [CI], 2.78-4.39) of developing any head and neck cancers compared to those without the disorder. The risk was particularly elevated for oral (RR, 2.51; 95% CI, 1.81-3.47), oropharyngeal (RR, 4.90; 95% CI, 2.99-8.02), and laryngeal cancers (RR, 8.39; 95% CI, 4.72-14.90).
The incidence of any head and neck cancer any time after the index event was 0.285% in the cannabis use disorder group compared to 0.091% in the non–cannabis use disorder group. For specific head and neck cancer subsites, the cannabis use disorder group had higher incidence rates of laryngeal cancer (0.093% vs 0.015%), oral cancer (0.113% vs 0.049%), and oropharyngeal cancer (0.081% vs 0.013%) than the non–cannabis use disorder group.
The associations remained significant when considering head and neck cancer cases diagnosed at least 1 year after cannabis use disorder diagnosis, with relative risks increasing to 4.40 (95% CI, 3.21-6.01) for any head and neck cancer, 3.11 (95% CI, 2.02-4.80) for oral cancer, and 6.70 (95% CI, 3.45-13.03) for oropharyngeal cancer. When considering head and neck cancer cases diagnosed at least 5 years after the index event, the relative risk for any head and neck cancer remained significant—at 5.00 (95% CI, 2.62-9.56)—in the cannabis use disorder group.
The findings were generally consistent when stratified by age. In the younger adult subgroup (< 60 years), the relative risk for any head and neck cancer was 3.44 (95% CI, 2.32-5.10), with significantly elevated risks for laryngeal, oral, and oropharyngeal cancers. For older adults (≥ 60 years), the relative risk for any head and neck cancer was 3.21 (95% CI, 2.44-4.21), with increased risks for laryngeal, oral, and oropharyngeal cancers.
The absolute risk increase for any head and neck cancer was 0.20% (95% CI, 0.17%-0.24%) in the cannabis use disorder group, with a number needed to harm of 500.
The authors discussed potential biological mechanisms linking cannabis use to head and neck cancer, including the inflammatory effects of cannabis smoke, which contains carcinogens similar to those in tobacco smoke, and the role of tetrahydrocannabinol in activating enzymes that convert polycyclic aromatic hydrocarbons into carcinogens.
While the study's findings suggested a potential causal link between cannabis use and head and neck cancer, the authors noted several limitations, including the lack of detailed information on cannabis use frequency and dosage, potential underreporting of cannabis use, and the possibility of missed head and neck cancer diagnoses if individuals received care outside participating organizations. They also acknowledged the potential for residual confounding from alcohol and tobacco use, despite controlling for these factors.
The study's findings contrast with some previous research that found no significant association between cannabis use and head and neck cancer, possibly due to differences in study design and sample size. The authors emphasized the need for future research to examine the mechanism of this association and analyze dose response with strong controls to further support evidence of cannabis use as a risk factor for head and neck cancers.
Given the rising trends in cannabis use and legalization, the authors noted that these findings have substantial public health implications. They called for additional studies using similarly large cohorts but with more thorough data on cannabis use—including dosage, frequency, and method of use—to confirm and expand upon these results.
The authors declared having no competing interests.
