Head and neck cancers squamous cell cancers (HNC) are the 6^th most common cancers worldwide. Major risk factors include alcohol, tobacco and human papillomavirus (HPV) infection. Marijuana (Cannabis sativa) contains more than 60 cannabinoids and smoke generated from these compounds is regarded as potential carcinogens. Previous publications have been contradictory with some suggesting marijuana use increases the risk of HNC while others have suggested a protective effect.

The aim of this review was to assess whether marijuana use favours the development of HNC

Methods

Searches were conducted in the Cochrane Library, Pubmed, Lilacs, Embase, BBO, and Bireme SciELO databases. Case–control studies, cohort or systematic reviews with cases having a definitive diagnosis of HNC, and controls matched at least by gender and age were considered. 3 reviewers carried out study selection independently. Methodological quality was assessed on a numerical scale based on the STROBE statement. The value of effect odds ratio (OR) was calculated, which represented the chance of developing head and neck cancer between individuals who had smoked marijuana in their lifetime in models controlled for age, gender, race, and tobacco consumption.

Results

• 10 studies met the inclusion criteria
• All 10 studies were considered to be of high quality
• Only 6 studies reporting 9 case-controlled studies were included in a meta-analysis
• Approximately 12.6% of the cases and 14.3% of the controls were marijuana users.
• No association between marijuana and head and neck cancer was found OR= 1.021; (95%CI; 0.912-1.14; p=0.718).

Conclusions

The authors concluded

No association between lifetime marijuana use and the development of head and neck cancer was found. The different methods of collection/presentation of results in the selected articles prevented other analyzes from being conducted. Additional studies are needed to assess for long-term effects.

Comments

The search for studies encompassed a number of well-known databases and 6 studies presenting 9 case-controlled studies have been included from 10 studies meeting the review criteria. However the authors have only conducted a simple meta-analysis as they indicate that while a range of variables such as type, method, quantity, and frequency of use, age of onset, years of use, and cumulative use were investigated by the individual studies variations in the methodology precluded this approach.

Interestingly while mentioned as a study meeting their criteria the pooled analysis conducted on individual-level data from nine case-control studies from the United States and Latin America by the INHANCE consortium (Marks et al 2014 ) was not included in the discussion. Seven of the studies included in this new review were included in the detailed INHANCE analysis.

They found

• Compared with never marijuana smokers, ever marijuana smokers had an elevated risk of oropharyngeal [adjusted OR (aOR)= 1.24; 95% CI; 1.06–1.47] and a reduced risk of oral tongue cancer aOR=0.47; (95% CI; 0.29, 0.75). The risk of oropharyngeal cancer remained elevated among never tobacco and alcohol users.
• The risk of oral tongue cancer was reduced among never users of tobacco and alcohol.
• Sensitivity analysis adjusting for potential confounding by HPV exposure attenuated the association of marijuana use with oropharyngeal cancer aOR = 0.99; (95% CI; 0.71–1.25), but had no effect on the oral tongue cancer association

Consequently they noted that,   the association of marijuana use with head and neck carcinoma may differ by tumor site.

The INHANCE review is more detailed than this current review and included sensitivity analyses that modeled the effects of differential and non differential misclassification of marijuana exposure which demonstrated that correction for misclassification did alter the strength of the association with each cancer outcome.

The differing associations of marijuana use with oropharyngeal and oral tongue cancer are consistent with both possible pro- and anticarcinogenic effects of cannabinoids.

Links

Primary paper

de Carvalho MF, Dourado MR, Fernandes IB, Araújo CT, Mesquita AT, Ramos-Jorge ML. Head and neck cancer among marijuana users: a meta-analysis of matched case-control studies. Arch Oral Biol. 2015 Dec;60(12):1750-5. doi: 10.1016/j.archoralbio.2015.09.009. Epub 2015 Sep 15. Review. PubMed PMID: 26433192.

Other references

STROBE Statement

Marks MA, Chaturvedi AK, Kelsey K, et al. Association of marijuana smoking with oropharyngeal and oral tongue cancers: pooled analysis from the INHANCE consortium. Cancer Epidemiol Biomarkers Prev. 2014 Jan;23(1):160-71. doi: 10.1158/1055-9965.EPI-13-0181. Epub 2013 Dec 18. PubMed PMID: 24351902; PubMed Central PMCID: PMC3947141.

The INHANCE consortium