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Oral cavity, pharyngeal, and laryngeal cancers may be referred to as head and neck squamous cell cancers. Head and neck squamous cell cancers most commonly arise from the mucosal surfaces lining the oral cavity, pharynx, and larynx. Pharyngeal squamous cell cancers are further categorized into nasopharyngeal, oropharyngeal, and hypopharyngeal cancers on the basis of anatomical landmarks (refer to the PDQ summaries on Laryngeal Cancer Treatment (Adult), Lip and Oral Cavity Cancer Treatment (Adult), Nasopharyngeal Cancer Treatment (Adult), and Oropharyngeal Cancer Treatment (Adult) for more information). Figure 1 shows the anatomy of the pharynx.
Figure 1. Anatomy of the pharynx.
Who Is at Risk?
Head and neck squamous cell cancers have common risk factors. People who use tobacco in any of the commonly available forms (cigarettes, cigars, pipes, and smokeless tobacco) or have a high alcohol intake are at elevated risk of oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers; they are at particularly high risk if they use both tobacco and alcohol. Individuals who chew betel quid (whether mixed with tobacco or not) are also at high risk of cancer of the oral cavity and oropharynx.[1,2] Individuals who have a personal history of cancer of the head and neck region also are at elevated risk of a future primary cancer of the oral cavity or oropharynx. Human papillomavirus (HPV) 16 is a sufficient, but not necessary, cause of oral, tongue, and oropharyngeal cancers. Risk factors for nasopharyngeal cancer include heavy alcohol intake, family history, Chinese and other Asian ancestry, and Epstein-Barr virus (EBV)–persistent infection; smoking is not a risk factor for nasopharyngeal cancer.[5,6]
Note: Separate PDQ summaries on Oral Cavity, Pharyngeal, and Laryngeal Cancer Screening and Cigarette Smoking: Health Risks and How to Quit are also available.
Factors With Adequate Evidence of an Increased Risk of Oral Cavity, Pharyngeal, and Laryngeal Cancers
Based on solid evidence from numerous observational studies, tobacco use increases the risk of cancers of the oral cavity and oropharynx, hypopharynx, and larynx.[7,8,9]
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, oropharynx, hypopharynx, and larynx are attributable to the use of tobacco products.
Based on solid evidence, alcohol use is a risk factor for the development of head and neck cancers. Its effects are independent of those of tobacco use.[10,11,12,13]
Magnitude of Effect: Lower than the risk associated with tobacco use, but the risk is approximately fivefold for people who drink five or more alcoholic beverages per day compared with nondrinkers, and is dose related.
Tobacco and alcohol use
Oral cavity, oropharynx, hypopharynx, and laryngeal cancers risk is highest in people who consume large amounts of both alcohol and tobacco. When both risk factors are present, the risk of cancer is greater than a simple multiplicative effect of the two individual risks.[11,14]
Magnitude of Effect: About two to three times greater for oral cavity and oropharyngeal cancers 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.[11,14,15]
Based on solid evidence, chewing betel quid alone or with added tobacco (gutka) increases the risk of both oral cavity and oropharyngeal cancers.[1,2] 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 of oropharyngeal cancer.
Human papillomavirus (HPV) infection
Based on solid evidence, HPV 16 infection causes oropharyngeal cancer.[4,16] Other high-risk HPV subtypes, including HPV 18, have been found in a small percentage of oropharyngeal cancers.[17,18]
Tobacco and alcohol use does not appear to be a major risk factor among people with evidence of HPV 16 L1 seropositivity or oral HPV 16 infection.
Magnitude of Effect: Large. Oral infection with HPV 16 confers about a 15-fold increase in risk of oropharyngeal cancer relative to individuals without oral HPV 16 infection.
Epstein Barr virus (EBV) infection
Based on solid evidence, EBV infection causes nasopharyngeal cancer in high-incidence areas. Collective evidence includes numerous case-control studies and cohort studies that show a higher proportion of patients with nasopharyngeal cancer who have anti-EBV antibodies than controls and that seropositive status precedes tumor diagnosis.[19,20] Recent studies have also found circulating cell-free EBV DNA in patients with nasopharyngeal cancer but not in controls. EBV alone is not a sufficient cause because 90% of adults worldwide are infected with the virus, but only a small proportion develop nasopharyngeal cancer.
Magnitude of Effect: Large. Infection with EBV confers an increase in risk that is more than 33-fold higher than that in individuals without EBV infection.
Interventions With Adequate Evidence of a Decreased Risk of Oral Cavity, Pharyngeal, and Laryngeal Cancers
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 oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers 20 years or longer after cessation.
Magnitude of Effect: Decreased risk, moderate to large magnitude.
Interventions With Inadequate Evidence of a Reduced Risk of Oral Cavity, Pharyngeal, and Laryngeal Cancers
Cessation of alcohol consumption
Based on fair evidence, cessation of alcohol consumption leads to a decrease in oral cavity cancer, 20 years or more after cessation. There is no evidence of a decrease in laryngeal cancer with alcohol cessation.
Magnitude of Effect: Decreased risk, small to moderate magnitude.
Vaccination against HPV 16 and the other high-risk subtypes
Vaccination against HPV 16 and 18 has been shown to prevent approximately 90% of oral HPV 16/18 infections within 4 years of vaccination. 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.
Incidence and Mortality
Oral cavity and oropharynx cancers
From 2010 to 2014, the estimated age-adjusted incidence of cancer of the oral cavity and oropharynx 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. It is estimated that there will be 51,540 new cases of oral cavity and oropharynx cancer diagnosed in the United States in 2018 and 10,030 deaths due to this disease. 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.
Although localized cancers of the oral cavity and oropharynx 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%.
Laryngeal cancers are less common with an annual incidence of 3 cases per 100,000 persons. It is estimated that 13,150 new cases will be diagnosed in 2018, and an estimated 3,710 individuals will die from the disease. The 5-year survival rate for laryngeal cancer is 61%. New cases of laryngeal cancer have been falling an average of 2.4% per year over the last 10 years. This has been attributed to a reduction in cigarette smoking.
Hypopharyngeal cancers are rare with approximately 2,500 new cases diagnosed in the United States each year and an annual incidence of 0.7 cases per 100,000 persons.[2,4] The 5-year survival rate for hypopharyngeal cancer is 26%. New cases have been falling an average of 2% per year over the last 20 years. This has been attributed to a reduction in cigarette smoking.
Nasopharyngeal cancers are rare in the United States with an annual incidence rate of 0.7 cases per 100,000 persons. However, there are marked geographic differences with an overall incidence in China that is 40- to 380-fold higher compared with the United States. There are elevated rates of nasopharyngeal cancers in the Cantonese population of southern China (including Hong Kong), and intermediate rates are observed in several indigenous populations in Southeast Asia, and in natives of the Arctic region, North Africa, the Middle East, and southern China. First-generation Chinese immigrants to the United States maintain a high incidence rate, while their descendants born in the United States show a decreased incidence. The 5-year survival rate for keratinizing squamous cell carcinoma, the most common subtype of nasopharyngeal cancer in the United States, is 46%.
Tobacco use is implicated in most cases of oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers. 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.[8,9] Epidemiologic studies consistently demonstrate that cigarette smokers have a higher incidence of mortality from head and neck squamous cell 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 (RR) 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. 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 southeast Asia, including China and India, and is an important risk factor for both oral cavity and oropharyngeal cancers.
Alcohol use is a major independent risk factor for the development of head and neck squamous cell cancer. Most epidemiologic studies demonstrate an increase in risk with increasing drinks per day, with a more than fivefold to six fold increase in risk for individuals who consume five or more drinks a day relative to nonconsumers.[11,12] Associations are observed in studies that control for confounding by smoking, as well as in studies of nonsmokers. There is a suggestion that consumption of beer and hard liquor confers a greater risk than does wine consumption.
Head and neck squamous cell 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 typically about two to three times greater than a simple multiplicative or additive effect. In a case-control study, individuals who consumed two or more packs of cigarettes and more than four alcoholic drinks per day had slightly more than a 35-fold increased risk of developing oral cavity or oropharyngeal cancer, relative to individuals who neither smoked nor drank. In a case-control study of laryngeal cancer, combined alcohol and tobacco consumption showed a multiplicative effect (odds ratio [OR], 177) rather than an additive risk.
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.[8,14] The carcinogenic component of chewed betel quid arises from the areca nut.
RRs are typically stronger for gutka than for betel quid alone. 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. Studies of head and neck cancer (without specification of subsite) suggest that increases in risk are positively correlated with chewing frequency and duration.
HPV 16 infection is a sufficient, but not necessary, cause of head and neck cancers, with a greater causal relationship with oropharyngeal cancer.[15,16] A meta-analysis of five case-control studies of HPV 16 positivity in either serum or tissue calculated an OR of 15.1 (95% confidence interval [CI], 6.8–33.7) for cancer of the tonsils, 4.3 (95% CI, 2.1–8.9) for other oropharyngeal sites, and 2.0 for both oral cavity (95% CI, 1.2–3.4) and larynx (95% CI, 1.0–4.2). 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. A recent national survey observed that men have a higher prevalence of oral HPV than women (11.5% vs. 3.2%), including high-risk HPV subtypes (7.3% men; 1.4% women).
Other high-risk HPV subtypes, including HPV 18, have been found in a small percentage of oropharyngeal cancers.[17,19] Given its association with cervical cancer, HPV 18 is believed to increase oropharyngeal cancer risk as well.
Based on solid evidence, EBV infection causes nasopharyngeal cancer in high-incidence areas. One of the first studies to show an association was a cohort study that found higher anti-EBV titers in 84% of the 235 East African and Chinese patients with nasopharyngeal carcinoma. The same study found higher anti-EBV titers with higher-stage tumor, and a case-control component of the study revealed that high anti-EBV titers were six times more likely in patients with nasopharyngeal carcinoma than in with patients with head and neck cancers at other sites.
Other studies show elevation in both IgG and IgA antibody titers to EBV viral capsid antigen and other latent viral antigens, which precede tumor development by several years and are correlated with tumor burden, remission, and recurrence.[21,22] A large cohort study with 9,699 men measured both IgA antibodies against EBV capsid antigen and neutralizing antibodies against EBV-specific DNase and followed them for a later diagnosis of nasopharyngeal cancer. The RR of nasopharyngeal carcinoma was 32.8 for individuals with both antibody markers (95% CI, 7.3–147.2; P < .001), and 4.0 for individuals with one marker (95% CI, 1.6–10.2; P = .003), compared with individuals with neither marker. There was a temporal relationship in that the difference in cumulative incidence between seropositive and seronegative patients increased with a longer duration of follow-up. Another study found circulating cell-free EBV DNA in 95% of patients with advanced nasopharyngeal cancer but not in controls or cured patients.
EBV infection is subclinical and occurs early in childhood. EBV alone is not a sufficient cause because 90% of adults worldwide are infected with the virus, but only a small proportion of them develop nasopharyngeal cancer. The pathogenesis is thought to involve the virus establishing latency in epithelial cells that have already undergone premalignant genetic changes.
The cessation of cigarette smoking is associated with an approximately 50% reduction in risk of developing oral cavity and oropharyngeal cancer within 5 to 9 years  and a return to a cancer risk comparable to that of never-smokers within 20 years.
A case-control study matched 527 individuals with laryngeal cancer to 1,297 hospital controls and found that compared with never-smokers, smokers had a 20-fold increased risk of cancer and exsmokers had a 7-fold increased risk.
Dentists can participate in the full scope of pharmacological and behavioral interventions for smoking cessation. A study has shown that only 25% of tobacco users report receiving advice to quit tobacco use from their dentists, a proportion less than tobacco users who received such advice from their physicians.
Because alcohol is associated with oral cavity and oropharyngeal cancer in a dose-dependent fashion,[13,27,28,29] 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. 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% 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. A case-control study of risk factors for laryngeal cancer found that alcohol cessation had no favorable effect on cancer risk.
Vaccination against HPV 16 and other high-risk subtypes
Vaccination against HPV 16 and 18 has been shown to prevent approximately 90% of oral HPV 16/18 infections within 4 years of vaccination.[30,31]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.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
This summary is written and maintained by the PDQ Screening and Prevention Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about oral cavity, pharyngeal, and laryngeal cancer prevention. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
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Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Screening and Prevention Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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PDQ® Screening and Prevention Editorial Board. PDQ Oral Cavity, Pharyngeal, and Laryngeal Cancer Prevention. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/head-and-neck/hp/oral-prevention-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389416]
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Last Revised: 2018-06-22
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