Etiology and Biology of Oral Cancer
Avoidance and Cessation of Tobacco Use
Alcohol Avoidance and Cessation
Avoidance of HPV Infection
Dietary Changes
Sunblock
Secondary Prevention

Etiology and Biology of Oral Cancer

Tobacco use is responsible for more than 90% of tumors of the oral cavity among men and 60% among women,[1] and is responsible for 90% of oral cancer deaths in males.[2] All forms of tobacco—cigarettes, pipes, cigars, and smokeless tobacco—have been implicated in the development of oral cancers.[3] While tobacco confers the highest risk for cancer of the floor of the mouth,[4] it is associated with an increased risk for all sites of oral cancer.

Alcohol use is a second independent major risk factor for the development of oral cancer.[5-8] There is a suggestion that beer and hard liquor confer a greater risk than wine.[5] 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.[5] 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.[9]

Carcinoma of the lip, predominantly on the lower lip, occurs in approximately 3,600 persons per year. Epidemiologically, these tumors behave akin to squamous cell carcinoma of the skin, and most are related to sun exposure, although chronic direct exposure to tobacco (i.e., the location where a pipe or cigarette is habitually held) is also associated with an increased risk of carcinoma of the lip.[10,11]

There appears to be an association between human papillomavirus (HPV) and oral cancer, particularly HPV type 16,[12-14] as shown in multiple case-control studies.[15] The role of HPV in the etiology of oral cancers, however, remains unclear. Independently, its association with oral cancer is lower than tobacco or alcohol, although it may modify the effect of these two substances.

Tobacco use is known to cause “field cancerization” resulting in a propensity for development of second primary tumors in patients with oral cancer. Oral squamous cell carcinomas are often preceded by oral preneoplastic lesions, which are often present as visible alterations of the mucosal surface and include leukoplakia and erythroplakia.[16] Studies utilizing a variety of chemopreventive interventions have demonstrated promising results for induction of apoptosis in oral malignant and premalignant cells.[17]

The cessation of cigarette smoking is associated with a 50% reduction of risk of developing oral cancer within 3 to 5 years [18] and a return to normal level of risk for development of oral cancer within 10 years.[5]

Dentists and other health professionals can play an integral role in smoking cessation advice and encouragement. Dentists can also participate in the full scope of pharmacological and behavioral interventions for smoking cessation.[19] A study has shown that only 25% of tobacco users report receiving advice to quit tobacco use from their dentist,[20] a proportion less than that received from their physician.

There was a dramatic increase in the use of cigars of about 250% during the period between 1993 and 1998 [21] and heavy cigar use is particularly associated with oral cancer development. Multiple case reports have implicated marijuana use as a cause of oral cancer, particularly in younger patients.[22]

Because alcohol is associated with oral cancer in a dose-dependent fashion,[4,5,23,24] it is believed that cessation or avoidance of alcohol would result in a lower incidence of oral cancer. The evidence is inadequate, however, of reduced oral cancer among people who have stopped consuming alcohol.

Association with HPV16 positive head and neck squamous cell carcinoma (HNSCC) is independently associated with several measures of sexual behavior and exposure to marijuana, but not with cumulative measures of the usual risk factors of tobacco smoking, alcohol drinking, and poor oral hygiene. Additionally, marijuana use may interact with high-risk HPV infection to promote HNSCC. Data are not available to determine if restricting these exposures will impact overall incidence or outcome of oral cancer.[25]

Several studies have shown an inverse association of fruit intake and the development of oral cancer, particularly in those who use tobacco.[4,23,26-28] Fiber, in the form of vegetable intake, has similarly been shown to be associated with a decreased risk of oral cancer. It is estimated that intake of fruits and vegetables may lower the risk of development of oral cancer by 30% to 50%.[26,29,30] The evidence is inadequate, however, of reduced oral cancer among people who have made changes in their diet.

The majority of cases of carcinoma of the lip occur on the lower lip, which has greater sun exposure than the upper lip. While tobacco has been strongly associated with lip cancer, sun exposure represents an important factor as well, and a consistent finding has been a correlation between the risk of lip cancer and the amount of time spent outdoors. Sunscreen use has been associated with a lower incidence of skin cancers [31,32] and thus may lower the incidence of lip cancer. In a study of women in Los Angeles, a very strong reduction in the risk of lip cancer was found to be associated with the daily use of lip protection (mostly colored lipstick).[10] Lip balm with sun protection is widely available.

Agents for the reversal or prevention of recurrence of oral lesions that sometimes progress to cancer are being addressed. One randomized controlled trial [33] found a protective effect of fenretinide against development of relapse and new leukoplakias during 1 year of fenretinide treatment. The study had insufficient power to determine the effect on oral cancer incidence due to premature closure of the study. Other agents are under clinical evaluation for treatment of oral premalignant lesions.[34-36]

References

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