Factors associated with increased risk of oral cancer
Tobacco use is responsible for more than 90% of tumors of the oral cavity among men and 60% among women, and is responsible for 90% of oral cancer deaths in males. All forms of tobacco—cigarettes, pipes, cigars, and smokeless tobacco—have been implicated in the development of oral cancers. While tobacco confers the highest risk for cancer of the floor of the mouth, it is associated with an increased risk for all sites of oral cancer.
Tobacco use is known to cause "field cancerization" resulting in a propensity for development of second primary tumors in patients with oral cancer. Case reports have also implicated marijuana smoking as a cause of oral cancer, particularly in younger patients.
Alcohol use is a second independent major risk factor for the development of oral cancer.[11,12,13,14] There is a suggestion that beer and hard liquor confer a greater risk than wine. The risk of oral cancer increases with the number of cigarettes smoked per day and the number of alcoholic drinks consumed per day in a dose-dependent fashion. The combined use of alcohol and tobacco increases the risk for oral cancer far greater than either independently. Alcohol use has been shown to be an independent risk factor for development of oral premalignant lesions (leukoplakia or erythroplakia), which can progress to cancer.
Human papillomavirus (HPV) infection
There is an association between HPV and oral cancer, particularly HPV type 16 as shown in multiple case-control studies.[16,17,18,19,20,21,22] HPV 16 accounts for 90% to 95% of HPV-positive oropharyngeal tumors, but other high-risk subtypes include 18, 31, 33, and 35. The mechanism of HPV in the etiology of oral cancers may be related to its oncoproteins E6 and E7, which bind to and trigger the degradation of the p53 and pRB tumor suppressor proteins, respectively. HPV accounts for a relatively small proportion of oropharyngeal cancers compared to tobacco and alcohol. However, the rates of HPV-associated oropharyngeal cancers appear to be increasing.[20,23]