How Marijuana Accelerates Growth of HPV-related Head and Neck Cancer

The ingredient that causes the high associated with cannabis, tetrahydrocannabinol (THC), has been identified as the molecular mechanism that fast-tracks cancer growth in patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma, according to research led by the University of California San Diego School of Medicine.

Previous studies have linked daily marijuana use to an increased prevalence of HPV-related throat cancer, but the mechanism linking cannabis exposure to increased growth of the cancer was unknown. The study, “Cannabinoids Promote Progression of HPV Positive Head and Neck Squamous Cell Carcinoma via p38 MAPK Activation,” suggests THC’s presence in the bloodstream stimulates the p38 MAPK pathway and prevents apoptosis from occurring, thus allowing cancer cells to grow uncontrollably.

The paper published in Clinical Cancer Research describes how THC works through CB1 and CB2 receptors—members of G protein coupled receptors—to direct the p38 MAPK pathway—a well-known pathway that prompts cells to grow and invade.

“This study shows that cannabis and marijuana contribute to the development of HPV-related throat cancer. Since this cancer incidence is rapidly rising, this provides evidence this is likely related to marijuana exposure, in combination with viral infection of the throat with HPV,” says Joseph A. Califano III, MD, senior author and a professor and vice chief of the Division of Otolaryngology in the Department of Surgery at UC San Diego School of Medicine, director of the Head and Neck Cancer Center at Moores Cancer Center at UC San Diego Health, and physician-in-chief at Moores Cancer Center.

The team used animal and human cell lines to show that THC turns on p38 MAPK. They also demonstrated that HPV-positive head and neck cancer growth stopped by turning off the pathway. Researchers then analyzed blood samples from patients with HPV-related throat cancer who had their genomes comprehensively mapped to define activated gene pathways. Blood samples from patients with THC in their blood showed p38 MAPK activation and loss of apoptosis in tumors, according to the study.

Legalization of cannabis in 33 states for either medical or recreational use has resulted in an increase in its use. In previous years, the United States witnessed a decrease in the rate of new cases of HPV-related oral cavity and oropharyngeal cancers. But there has been an increase in cases of oropharyngeal cancer linked to HPV in both men and women. According to the US Centers for Disease Control and Prevention, approximately 44,000 new cases of HPV-associated cancers occurred in the US between 2012 and 2016. HPV is estimated to cause 34,800 of these cancers.

HPV is the most common sexually transmitted infection in the US, and is estimated to cause 70% of oropharyngeal cancers, according to the CDC. For this reason, oral health professionals should educate patients about the oral risks associated with cannabis, spot symptoms of HPV-oral cancers during the oral cancer screening, and promote HPV vaccination by discussing the association between the virus to HPV-related cancers and viruses.

“The HPV vaccine is highly effective and greatly reduces the incidence of HPV-related cervical cancer. Counseling patients to get the vaccine is the best way to prevent this cancer,” says Califano. “The important thing is that 9- to 16-year-old boys and girls get the vaccine.”

 While some patients may readily disclose marijuana use on the medical history form, others may be hesitant to discuss its use. Clinicians should be prepared to ask follow-up questions if patients check “yes” to using cannabis, and be able to distinguish the signs of marijuana use in patients who do not disclose its use.

 These findings suggest daily cannabis use has adverse effects on oral health and systemic health, and suggests THC and cannabis products described as having cancer-fighting properties need additional evaluation. Cancer patients using cannabis for pain and/or symptom management should be advised of risks associated with these products.

 “I advise my patients with HPV-related throat cancer not to use cannabis products. However, for other cancers, there are no data on the effects, so it would be reasonable to continue use,” says Califano.  However, researchers say more research is needed on the association between marijuana and THC compounds as stimulating cancer growth in other cancers.

The team now is investigating whether p38 MAPK can be targeted with drugs to stop HPV-related head and neck cancers from growing, and is also exploring whether cannabidiol, or CBD, has a similar effect to THC.