Cannabis use may significantly raise risk for this cancer
MDlinx Sep 06, 2024
Head and neck cancer (HNC) accounts for approximately 3.0% of all cancers and more than 1.5% of all cancer mortality in the United States. HNC has historically been linked to smoking and excessive alcohol intake. In recent years, however, there has been a focus on other modifiable risk factors (eg, HPV infection), which are integral to lowering the prevalence of HNC
Gallagher TJ, Chung RS, Lin ME, et al. Cannabis use and head and neck cancer. JAMA Otolaryngol Head Neck Surg. 2024 Aug 8:e242419.
—heavy cannabis use may be one of them.
Cannabis is the most common illicit drug globally, typically ingested via smoking. Cannabinoid derivatives trigger unique gene expression profiles, oxidative stressors, and inflammatory pathways in the human body.
Gallagher TJ, Chung RS, Lin ME, et al. Cannabis use and head and neck cancer. JAMA Otolaryngol Head Neck Surg. 2024 Aug 8:e242419.
Results of studies correlating cannabis and HNC risk are mixed; it remains to be elucidated whether the clinical relationship between cannabis use and HNC is comparable to that of tobacco use—but the latest research points to warning signs.
Potential carcinogenic mechanisms
Using a global database of electronic records called TriNetX, researchers at UCLA and Stanford hypothesized an association between cannabis use and HNC, secondary to the inflammatory effects of smoke on the upper airway, due to cannabis’s potential carcinogenic mechanisms. They published their results in JAMA Otolaryngology-Head & Neck Surgery.
Gallagher TJ, Chung RS, Lin ME, et al. Cannabis use and head and neck cancer. JAMA Otolaryngol Head Neck Surg. 2024 Aug 8:e242419.
In this large cohort study, the investigators mined 20 years of medical records from 64 healthcare organizations. They identified US adults with cannabis-use disorders (n = 116,076) and without cannabis-related disorders (n = 3,985,286) and no previous medical history of HNC. They also analyzed patients aged younger than 60 years and 60 years or older. The cohorts were propensity-score matched, and relative risks were calculated to assess the risk of HNC, including HNC subsites.
There was a higher rate of new HNC diagnosis in all sites in the cannabis-related disorder cohort. Patients with cannabis-related disorders were at greater risk for any HNC (RR, 3.49; 95% CI, 2.78–4.39) compared to those without.
Site specifically, there was a higher rate of oral (RR, 2.51; 95% CI, 1.81-3.47); oropharyngeal (RR, 4.90; 95% CI, 2.99-8.02); and laryngeal (RR, 8.39; 95% CI, 4.72-14.90) cancer. Results were similar in both the older and younger age groups.
When the researchers expanded the scope to HNC cases occurring more than 1 year after diagnosis with cannabis-use disorder (ie, the index event), the correlations magnified. However, associations waned when considering cases that occurred 5 or more years after diagnosis. This could be due to uncontrolled factors, including poor sample sizes and inconsistent cannabis use.
Overall, the investigators found that diagnosis with cannabis-use disorder increased the risk of not only any HNC but also oral, oropharyngeal, nasopharyngeal, salivary gland, and laryngeal cancer vs matched individuals.
Put another way, the relative risk of developing HNC with cannabis-related disorders was between 3- and 5 times higher compared to those without the disorder. In contrast, the relative risk of developing HNC in the context of alcohol or tobacco use is between 2 and 10 times.
Worse than cigarette smoke?
The study authors pointed out that marijuana smoke may be even more pro-inflammatory than cigarette smoking. Cannabis smoke is typically unfiltered, inhaled in deeper breaths, and burns at a higher temperature than tobacco, which raises the risk of inflammatory injury.
Marijuana smoke increases the expression of epidermal growth factor receptors, which are overexpressed in most cases of squamous cell carcinoma in the head and neck, as well as in laryngeal cancer.
Although some studies have demonstrated the antitumor properties of cannabinoids, including the suppression of cancer proliferation and decreased angiogenesis of tumours, others have found that cannabis smoke could contribute to tumour formation via higher levels of oxidative stress and the inhibition of tumour-specific immune mechanisms.
The authors wrote that a mixed effect is not surprising, considering the cannabis plant produces more than 400 unique chemical entities and more than 60 cannabinoids with various contradictory effects.
As for whether cannabis can cause cancer, authors of a two-sample Mendelian randomization (MR) study published in the Journal of Cancer Research and Clinical Oncology investigated the causality of cannabis use on nine site-specific types of cancer, including laryngeal cancer.
Huang P, Zhang PF, Li Q. Causal relationship between cannabis use and cancer: a genetically informed perspective. J Cancer Res Clin Oncol. 2023 Sep;149(11):8631-8638.
They found a causative relationship between cannabis use and cervical cancer, as well as an association with increased odds of breast cancer and laryngeal cancer. These associations require “further evaluation in large-scale population-based studies.”
Huang P, Zhang PF, Li Q. Causal relationship between cannabis use and cancer: a genetically informed perspective. J Cancer Res Clin Oncol. 2023 Sep;149(11):8631-8638.
The California researchers commented that many small case-control studies, although burdened by limitations, have found a positive association of marijuana with oropharyngeal cancers and an inverse association with smoking-associated oral cancers at anatomic levels with high carcinogen exposure.
Gallagher TJ, Chung RS, Lin ME, et al. Cannabis use and head and neck cancer. JAMA Otolaryngol Head Neck Surg. 2024 Aug 8:e242419.
Health implications
Concurrent with the study report’s publication, the American Head and Neck Society provided an invited commentary to reflect on the study’s findings at their 2024 annual meeting.
Califano J, Sen P, Liu C. Cannabis and head and neck cancer–Déjà vu all over again? JAMA Otolaryngol Head Neck Surg. August 8, 2024. doi:10.1001/jamaoto.2024.2420.
The authors of the accompanying editorial decried similarities between marijuana and cigarette smoking, pointing out that, regarding cigarettes, the healthcare establishment was slow to react, and countless people lost their lives from cigarette smoking-related illnesses.
“Are we repeating the same mistakes of the past we made with smoking, only now with marijuana and cannabis? Are we watching cannabis use rapidly expand with the support of a powerful industry, the public, and our legislators, only to discover years later, after the genie has escaped the bottle, that cannabis is carcinogenic?” the authors wrote.
Califano J, Sen P, Liu C. Cannabis and head and neck cancer–Déjà vu all over again? JAMA Otolaryngol Head Neck Surg. August 8, 2024. doi:10.1001/jamaoto.2024.2420.
They stressed that it’s important to understand the biological differences and similarities between tobacco and cannabis in order to avoid this, noting that it's still unclear whether tobacco and cannabis have similar carcinogenic mechanisms.
“If cannabinoids themselves are primary carcinogenic drivers, then the addictive and psychoactive effects of cannabis may not be able to be separated from carcinogenic effects, unlike nicotine and tobacco smoke,” the authors explained.
Califano J, Sen P, Liu C. Cannabis and head and neck cancer–Déjà vu all over again? JAMA Otolaryngol Head Neck Surg. August 8, 2024. doi:10.1001/jamaoto.2024.2420.
What this means for you
Recent research shows that heavy cannabis use increases the risk of head and neck cancer, as cannabinoids may be drivers of carcinogenesis. One area of concern for specialists is to balance the potential of marijuana to treat symptoms of illness with its potentially carcinogenic properties.
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