Oral Cavity and Oropharyngeal Cancer Prevention (PDQ®)

Tobacco use

Based on solid evidence from numerous observational studies, tobacco use increases the risk of cancers of the oral cavity and oropharynx.[6-8] .

Magnitude of Effect: Large. Risk for current smokers is about tenfold that of never-smokers, and is dose related. Most cancers of the oral cavity are attributable to the use of tobacco products.

• Study Design: Numerous observational case-control and cohort studies.
• Internal Validity: Good.
• Consistency: Good.
• External Validity: Good.

Alcohol use

Based on solid evidence, alcohol use is a risk factor for the development of oral cavity and oropharyngeal cancer. Its effects are independent of those of tobacco use.[9-12]

Magnitude of Effect: Lower than the risk associated with tobacco use, but the risk is approximately doubled for people who drink three to four alcoholic beverages per day compared with nondrinkers, and is dose related.

• Study Design: Case-control and cohort studies.
• Internal Validity: Good.
• Consistency: Good.
• External Validity: Good.

Tobacco and alcohol use

Oral cavity and oropharyngeal cancer risk is highest in people who consume large amounts of both alcohol and tobacco. When both risk factors are present, the risk of oral cavity and oropharyngeal cancer is greater than a simple multiplicative effect of the two individual risks.[10,13]

Magnitude of Effect: About two to three times greater than the simple multiplicative effect, with risks for persons who both smoke and drink heavily approximately 35-fold that of persons who both never smoke and never drink.[10,13]

• Study Design: Case-control and cohort studies.
• Internal Validity: Good.
• Consistency: Good.
• External Validity: Good.

Betel-quid chewing

Based on solid evidence, chewing betel quid alone or with added tobacco (gutka) increases the risk of both oral cavity and oropharyngeal cancers.[3,14] Of the three primary components of betel quid (betel leaf, areca nut, and lime), the areca nut is the only one considered to be carcinogenic when chewed.

Magnitude of Effect: Relative risks for oral cavity cancer are high and typically stronger for gutka than for betel quid alone. Both products appear to confer a modest yet statistically significant increase in risk for oropharyngeal cancer.[3]

• Study Design: Ecologic, case-control, and cohort studies.
• Internal Validity: Good.
• Consistency: Good.
• External Validity: Good.

Tobacco cessation

Based on solid evidence, cessation of exposure to tobacco (e.g., cigarettes, pipes, cigars, and smokeless tobacco) leads to a decrease in the risk of cancer of the oral cavity and oropharynx.

Magnitude of Effect: Decreased risk, moderate to large magnitude.

• Study Design: Case-control and cohort studies.
• Internal Validity: Good.
• Consistency: Good.
• External Validity: Good.

Cessation of alcohol consumption

Based on fair evidence, cessation of alcohol consumption leads to a decrease in oral cavity cancer, but not until approximately 10 years after cessation. For cancer of the oropharynx, reduction in risk does not occur until approximately 20 years after cessation.[15]

Magnitude of Effect: Decreased risk, small to moderate magnitude.

• Study Design: Case-control studies.
• Internal Validity: Fair.
• Consistency: Fair.
• External Validity: Fair.

Human papillomavirus (HPV) infection

Based on solid evidence, HPV 16 infection causes oropharyngeal cancer.[5] HPV 16 is a sufficient but not necessary cause. Other high-risk HPV subtypes, including HPV 18, have been found in a small percentage of oropharyngeal cancers.[16,17]

Tobacco and alcohol use does not appear to be associated with increased risk among people with evidence of HPV 16 L1 seropositivity or oral HPV 16 infection.[16]

Magnitude of Effect: Large. Oral infection with HPV 16 confers about a 15-fold increase in risk relative to individuals without oral HPV 16 infection.

• Study Design: Case-control and cohort studies, including one conducted using data collected prospectively (nested case-control study).
• Internal Validity: Good.
• Consistency: Good.
• External Validity: Good.

Vaccination against HPV 16 and the other high-risk subtypes

Vaccination against HPV 16 and 18 has been shown to prevent more than 90% of oral HPV 16/18 infections within 4 years of vaccination.[18] However, no data are available to assess whether vaccination at any age will lead to reduced risk of oropharyngeal cancer at current typical ages of diagnosis.

• Study Design: No studies available.
• Internal Validity: Not applicable (N/A).
• Consistency: N/A.
• External Validity: N/A.

Incidence and mortality

From 2010 to 2014, the estimated age-adjusted incidence of cancer of the oral cavity and pharynx in the United States was 11.2 cases per 100,000 persons per year. The estimated mortality rate for the same years was 2.5 per 100,000 persons per year. U.S. incidence and mortality rates are both about 2.6 times higher in men than in women.[1] It is estimated that there will be 49,670 new cases of oral cavity and pharynx cancer diagnosed in the United States in 2017 and 9,700 deaths due to this disease.[2] Cancer of the oral cavity will account for about 45% and cancer of the oropharynx will account for about 20% of the estimated incidence.[3] In 2012, the estimated age-standardized (World Standard Population) worldwide incidence rate of oral cavity and pharyngeal cancer was about 7.0 per 100,000 persons per year; the estimated mortality rate was 3.9 per 100,000 persons per year.[4] Cancer of the oral cavity accounts for about one-half of the incidence and mortality estimates, and cancer of the oropharynx accounts for about one-third of the incidence and mortality estimates. Rates of oral cavity cancer vary greatly across the world, primarily because of differences in alcohol use, tobacco use, and betel-quid chewing and the products chewed. In 2012, for example, the rate of oral cavity cancer in French Guiana was 0 per 100,000 persons; in Papua New Guinea, the rate was 25 per 100,000 persons. Rates of oropharyngeal cancer vary as well but less so; in 2012, rates varied from 0 per 100,000 persons in a number of countries to about 9 per 100,000 persons in Bangladesh.[4]

Oral cavity cancer includes cancer of the tongue, gums, floor of the mouth, and other parts of the mouth. In the United States, oropharyngeal cancer is the most common pharyngeal cancer.[1] Squamous cell carcinoma, which arises from the oral mucosal lining, accounts for more than 90% of the tumors in the oral cavity and oropharynx. Leukoplakia, erythroplakia, and erythroplasia are considered preneoplastic lesions, but most will not progress to carcinoma.[5]

The most important factor affecting long-term outcome after treatment is the stage of disease at diagnosis; however, overall outcome is stage and site dependent. Although localized cancers of the oral cavity and pharynx have an excellent anticipated 5-year survival rate of about 83%, the 5-year survival rate for patients with regional lymph node spread is only about 62%; the 5-year survival rate for patients with metastases is about 38%.[6] Separate stage-specific survival rates for oral cavity and oropharyngeal cancer are not available.

Tobacco use

Tobacco use is implicated in most cases of oral cavity and oropharyngeal cancer.[7] All forms of tobacco use (cigarettes, pipes, cigars, snuff, chewing tobacco, gutka [betel quid with tobacco added], and other smoked and smokeless products) increase the risk of these cancers.[8] Epidemiologic studies consistently demonstrate that cigarette smokers have a higher incidence of mortality from oral cavity and oropharyngeal cancers compared with lifetime nonsmokers, and there is general consensus that the relationship is causal. Among current smokers who smoke only cigarettes, the relative risk of cancer of the oral cavity or oropharynx was observed in a large cohort study to be approximately tenfold greater in men and fivefold greater in women compared with lifetime nonsmokers.[8] However, other epidemiologic studies have observed smaller and larger increases in risk, with some variation by anatomic location. Gutka chewing is prevalent in many countries in south and south-east Asia, including China and India, and is an important risk factor for both oral cavity and oropharyngeal cancer.[7]

Alcohol use

Alcohol use is a major independent risk factor for the development of oral cavity and oropharyngeal cancer.[9] Most epidemiologic studies demonstrate an increase in risk with increasing drinks per day, with a more than fivefold increase in risk for individuals who consume five or more drinks a day relative to nonconsumers.[10] Associations are observed in studies that control for confounding by smoking, as well as in studies of nonsmokers.[9] There is a suggestion that consumption of beer and hard liquor confers a greater risk than does wine consumption.[11]

Tobacco and alcohol use

Oral cavity and oropharyngeal cancer risk is highest in people who consume large amounts of both alcohol and tobacco.[10] When both risk factors are present, the risk of oral cavity and oropharyngeal cancer is typically about two to three times greater than a simple multiplicative effect.[11] In a case-control study, individuals who consumed two or more packs of cigarettes and more than four alcoholic drinks per day had slightly over a 35-fold increased risk for developing oral cavity or oropharyngeal cancer, relative to individuals who neither smoked nor drank.[11]

Betel-quid chewing

Betel quid is composed of betel leaf, areca nut, and lime; gutka is betel quid with added tobacco. Both betel-quid and gutka chewing increase the risk of cancer of the oral cavity and oropharynx.[7,12] The carcinogenic component of chewed betel quid arises from the areca nut.[7]

Relative risks are typically stronger for gutka than for betel quid alone.[12] A meta-analysis of oral cavity cancer studies conducted on the Indian subcontinent calculated a statistically significant eightfold increase in risk for gutka chewing and a statistically significant twofold increase in risk for betel-quid chewing. A statistically significant tenfold increase in oral cavity cancer risk for betel-quid chewing was demonstrated by studies conducted in China or Taiwan. A meta-analysis of oropharyngeal cancer studies conducted on the Indian subcontinent calculated a statistically significant fourfold increase in risk for gutka chewing and a statistically significant twofold increase in risk for betel-quid chewing.[12] Studies of head and neck cancer (without specification of subsite) suggest that increases in risk are positively correlated with chewing frequency and duration.[7]

Tobacco cessation

The cessation of cigarette smoking is associated with about a 50% reduction in risk of developing oral cavity and oropharyngeal cancer within 5 to 9 years [13] and a return to a cancer risk comparable to that of never-smokers within 20 years.[13]

Dentists can participate in the full scope of pharmacological and behavioral interventions for smoking cessation.[14] A study has shown that only 25% of tobacco users report receiving advice to quit tobacco use from their dentists,[15] a proportion less than tobacco users who received such advice from their physicians.

Cessation of alcohol consumption

Because alcohol is associated with oral cavity and oropharyngeal cancer in a dose-dependent fashion,[11,16- 18] it is believed that cessation or avoidance of alcohol use would result in reduced incidence. However, the evidence for reduced oral cavity and oropharyngeal cancer among people who have stopped consuming alcohol is inadequate.[13] Most studies suggest that the risk of oral cavity cancer decreases as time from cessation increases; one meta-analysis of eight studies observed a statistically significant 35% reduction (95% confidence interval [CI], 0.26–0.78), relative to current drinkers, for those who ceased consumption 20 years or more ago. Data for oropharyngeal cancer alone are not available, but studies that examine oropharyngeal cancer in conjunction with at least one other pharyngeal cancer typically have demonstrated a smaller risk reduction than for oral cavity cancer.[13]

Human papillomavirus (HPV) infection

HPV 16 infection is a sufficient, but not necessary, cause of oropharyngeal cancer.[19] It is, however, present in more than 85% of HPV-associated oropharyngeal cancers.[10] A meta-analysis of five case-control studies of HPV 16 positivity in either serum or tissue calculated an odds ratio of 4.3 (95% CI, 2.1–8.9) for oropharyngeal cancer.[20] In a case-control study, the observed strong association of HPV 16 serologic status and oropharyngeal cancer did not vary at different levels of tobacco or alcohol use.[21]

Other high-risk HPV subtypes, including HPV 18, have been found in a small percentage of oropharyngeal cancers.[21,22] Given its association with cervical cancer, HPV 18 is believed to increase oropharyngeal cancer risk as well.[22]

Vaccination against HPV 16 and other high-risk subtypes

Vaccination against HPV 16 and 18 has been shown to prevent more than 90% of oral HPV 16/18 infections within 4 years of vaccination.[23] Given the relatively recent adoption of vaccination and the age at which individuals are vaccinated, there is not yet evidence that vaccination at a young age will lead to a substantially reduced risk of HPV-associated oropharyngeal cancer later in life. In addition, no data are available to examine whether incidence or mortality would be reduced if vaccination occurred at an age closer to that at which oropharyngeal cancers tend to present.