Cannabinoids promote HPV-related head and neck cancer
THC promotes progression of HPV-related head and neck cancer
HPV-related head and neck squamous cell carcinoma has been increasing and is now the sixth most common cancer worldwide, particularly cases related to HPV infection. Starting in the mucous membranes that line the mouth, nose, and throat, previous studies have suggested a link to regular cannabis exposure; but until now a mechanism had not been identified. Research now published in the journal Clinical Cancer Research reveals that THC (tetrahydrocannabinol) in the bloodstream activates a pathway that prevents apoptosis, the normal process of programmed cell death. The authors state:
Human papilloma virus (HPV) related head and neck squamous cell carcinoma (HNSCC) is associated with daily marijuana use and is also increasing in parallel with increased marijuana use in the United States. Our study is designed to define the interaction between cannabinoids and HPV positive HNSCC.
Apoptosis inhibition by THC
Apoptosis, programmed cell death that eliminates cells that are old, unhealthy, or unnecessary without releasing harmful substances into the tissue environment, is turned off by the p38 MAPK pathway. When p38 MAPK is activated it can result in cancer cells growing uncontrollably. The authors analyzed the expression of cannabinoid receptors in HPV positive HNSCC (head and neck squamous cell carcinoma) and found that the activity of CNR1 and CNR2 receptors was elevated.
...the expression of CNR1 and CNR2 was elevated in HPV positive HNSCC compared with HPV negative HNSCC, and knockdown of CNR1/CNR2 expression inhibited proliferation in HPV positive HNSCC cell lines. Specific CNR1 and CNR2 activation as well as non-selective cannabinoid receptor activation in cell lines and animal models promoted cell growth, migration, and inhibited apoptosis through p38 MAPK pathway activation...CNR1/CNR2 antagonists suppressed cell proliferation and migration, and induced apoptosis.
Potentially huge public health problem
HPV-related head and neck cancer is increasing, HPV infection is so common that most will get at least one type during their life though it might not be noticed, cannabis exposure is increasing, and there is hesitancy regarding the vaccines that work best before a person has been exposed. Cancer Research from Technology Networks quotes Joseph A. Califano III, MD, senior author and professor and vice chief of the Division of Otolaryngology in the Department of Surgery at UC San Diego School of Medicine:
HPV-related head and neck cancer is one of the fastest growing cancers in the United States. While at the same time, exposure to marijuana is accelerating. This is a huge public health problem...We now have convincing scientific evidence that daily marijuana use can drive tumor growth in HPV-related head and neck cancer...Marijuana and other cannabis products are often considered benign, but it is important to note that all drugs that have benefits can also have drawbacks. This is a cautionary tale...Together, a low HPV vaccination rate and an increase in marijuana use among youth has the makings of a storm.
It should also be noted that the anti-inflammatory effect of cannabinoids exploited by many for pain relief may act by increasing immune tolerance. This can backfire in the context of infection or malignancy. The authors conclude:
Using whole genome expression analysis in a primary HPV HNSCC cohort, we identified specific p38 MAPK pathway activation signature in tumors from HPV HNSCC patients with objective measurement of concurrent cannabinoid exposure...Cannabinoids can promote progression of HPV positive HNSCC through p38 MAPK pathway activation.