Purpose of This PDQ Summary
Summary of Evidence

Avoidance of Tobacco Avoidance of Alcohol Dietary Factors Sun Exposure

Significance

Incidence and Mortality

Evidence of Benefit

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

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Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about oral cancer prevention. This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board ¹.

Information about the following is included in this summary:

• Oral cancer incidence and mortality statistics and information about oral cancer risk factors.
• Interventions for oral cancer prevention.
• Benefits of interventions to prevent oral cancer.

This summary is intended as a resource to inform clinicians and other health professionals about the currently available information on oral cancer prevention. The PDQ Screening and Prevention Editorial Board uses a formal evidence ranking system ² in reporting the evidence of benefit and potential harms associated with specific interventions. It does not provide formal guidelines or recommendations for making health care decisions. Information in this summary should not be used as a basis for reimbursement determinations.

This summary is also available in a patient version ³, which is written in less technical language.

Summary of Evidence

Note: Separate PDQ summaries on Oral Cancer Screening; ⁴ Lip and Oral Cavity Cancer Treatment; ⁵ and Prevention and Cessation of Cigarette Smoking: Control of Tobacco Use ⁶ are also available.

Based on solid evidence, avoidance or cessation of exposure to tobacco (e.g., cigarettes, pipes, cigars, and smokeless tobacco) would lead to a decrease in oral cancer.

Description of the Evidence

• Study Design: Evidence of association and reduced risk obtained from cohort or case-control studies.
• Internal Validity: Good.
• Consistency: Good.
• Magnitude of Effects on Health Outcomes: Decreased risk, moderate to large magnitude.
• External Validity: Good.

Although alcohol use is a risk factor for oral cancer, there is inadequate evidence that cessation of alcohol use decreases the risk of oral cancer.

Description of the Evidence

• Study Design: Evidence of association only from cohort or case-control studies.
• Internal Validity: Good.
• Consistency: Good.
• Magnitude of Effects on Health Outcomes: Decreased risk, moderate magnitude.
• External Validity: Good.

Oral cancer risk is highest in persons using both alcohol and tobacco, compared with those using one or the other.

There is inadequate evidence to determine whether a change in diet would decrease the risk of oral cancer.

Description of the Evidence

• Study Design: Evidence of association only obtained from cohort or case-control studies.
• Internal Validity: Inadequate.
• Consistency: Not applicable (N/A).
• Magnitude of Effects on Health Outcomes: N/A.
• External Validity: N/A.

There is inadequate evidence to determine whether reducing sun exposure would prevent lip cancer.

Description of the Evidence

• Study Design: Evidence of association only obtained from cohort or case-control studies.
• Internal Validity: Inadequate.
• Consistency: N/A.
• Magnitude of Effects on Health Outcomes: N/A.
• External Validity: N/A.

Significance

Incidence and Mortality

In 1998, the estimated incidence of oral cancer in the United States was 9.3 cases per 100,000 persons, with a mortality rate of 2.5 per 100,000 persons.[1] It is estimated that there will be 35,310 new cases of oral cancer diagnosed in the United States in 2008 and 7,590 deaths due to this disease.[2] Oral cancer is more common in men than in women and accounts for 3% of new cancer cases in men and 2% in women.[2] Oral cancer can be divided into three clinicopathological categories: carcinoma of the lip vermillion, carcinoma of the oral cavity proper, and carcinoma of the oropharynx. Most patients with cancer of the oral cavity are males, although incidence of tongue cancer in U.S. females has progressively increased from 15% in the 1930s to 47% between 1988 and 1997.

Squamous cell carcinoma, which arises from the oral mucosal lining, accounts for more than 90% of the tumors in the oral cavity and oropharynx. Other types of primary tumors arising in this area include lymphoma, sarcoma, melanoma, and minor salivary gland tumors. In the Western world the most common locations of tumor development are the tongue and floor of the mouth; however, in parts of the world where tobacco or betel nut chewing is prominent, cancers of the retromolar trigone and buccal mucosa are common.

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 early stage tumors (without lymph node involvement) have an excellent anticipated cure rate (~75%–95%), the 5-year disease-free survival rate of oral squamous cell carcinoma has not improved considerably over the past 50 years, and is poor (about 20%–50%), depending on the stage of disease. Some or all of the differences in prognosis among disease stages may be due to lead-time bias rather than a benefit of early detection and treatment. Definitive treatment consists of either surgery or radiation therapy for early stage tumors of the oral cavity, and combined modality treatment with surgery and/or chemotherapy can be used to treat more advanced stages.

References

1. Ries LA, Eisner MP, Kosary CL, et al., eds.: SEER Cancer Statistics Review 1973-1998. Bethesda, Md: National Cancer Institute, 2001. Also available online. ⁷ Last accessed July 30, 2008. 
   
   
2. American Cancer Society.: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Also available online. ⁸ Last accessed October 1, 2008. 
   
   

Evidence of Benefit

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

1. Reducing the Health Consequences of Smoking: 25 Years of Progress - a Report of the Surgeon General. Rockville, Md : U.S. Dept. of Health and Human Services Public Health Service, Centers for Disease Control, Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 1989. 
   
   
2. Cinciripini PM, McClure JB: Smoking cessation: recent developments in behavioral and pharmacologic interventions. Oncology (Huntingt) 12 (2): 249-56, 259; discussion 260, 265, 2, 1998.  [PUBMED Abstract]
   
   
3. Spitz MR, Newell GR: Descriptive epidemiology of squamous cell carcinoma of the upper aerodigestive tract. Cancer Bull 39(2): 79-81, 1987. 
   
   
4. Macfarlane GJ, Zheng T, Marshall JR, et al.: Alcohol, tobacco, diet and the risk of oral cancer: a pooled analysis of three case-control studies. Eur J Cancer B Oral Oncol 31B (3): 181-7, 1995.  [PUBMED Abstract]
   
   
5. Blot WJ, McLaughlin JK, Winn DM, et al.: Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res 48 (11): 3282-7, 1988.  [PUBMED Abstract]
   
   
6. Altieri A, Bosetti C, Gallus S, et al.: Wine, beer and spirits and risk of oral and pharyngeal cancer: a case-control study from Italy and Switzerland. Oral Oncol 40 (9): 904-9, 2004.  [PUBMED Abstract]
   
   
7. Talamini R, La Vecchia C, Levi F, et al.: Cancer of the oral cavity and pharynx in nonsmokers who drink alcohol and in nondrinkers who smoke tobacco. J Natl Cancer Inst 90 (24): 1901-3, 1998.  [PUBMED Abstract]
   
   
8. Talamini R, Franceschi S, Barra S, et al.: The role of alcohol in oral and pharyngeal cancer in non-smokers, and of tobacco in non-drinkers. Int J Cancer 46 (3): 391-3, 1990.  [PUBMED Abstract]
   
   
9. Hashibe M, Sankaranarayanan R, Thomas G, et al.: Alcohol drinking, body mass index and the risk of oral leukoplakia in an Indian population. Int J Cancer 88 (1): 129-34, 2000.  [PUBMED Abstract]
   
   
10. Pogoda JM, Preston-Martin S: Solar radiation, lip protection, and lip cancer risk in Los Angeles County women (California, United States). Cancer Causes Control 7 (4): 458-63, 1996.  [PUBMED Abstract]
    
    
11. Silverman S Jr, ed.: Oral Cancer. 4th ed. Hamilton, Canada: BC Decker, 1998. 
    
    
12. Schwartz SM, Daling JR, Doody DR, et al.: Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection. J Natl Cancer Inst 90 (21): 1626-36, 1998.  [PUBMED Abstract]
    
    
13. Mork J, Lie AK, Glattre E, et al.: Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med 344 (15): 1125-31, 2001.  [PUBMED Abstract]
    
    
14. D'Souza G, Kreimer AR, Viscidi R, et al.: Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356 (19): 1944-56, 2007.  [PUBMED Abstract]
    
    
15. Franceschi S, Muñoz N, Bosch XF, et al.: Human papillomavirus and cancers of the upper aerodigestive tract: a review of epidemiological and experimental evidence. Cancer Epidemiol Biomarkers Prev 5 (7): 567-75, 1996.  [PUBMED Abstract]
    
    
16. Noonan VL, Kabani S: Diagnosis and management of suspicious lesions of the oral cavity. Otolaryngol Clin North Am 38 (1): 21-35, vii, 2005.  [PUBMED Abstract]
    
    
17. Hsu S, Singh B, Schuster G: Induction of apoptosis in oral cancer cells: agents and mechanisms for potential therapy and prevention. Oral Oncol 40 (5): 461-73, 2004.  [PUBMED Abstract]
    
    
18. Samet JM: The health benefits of smoking cessation. Med Clin North Am 76 (2): 399-414, 1992.  [PUBMED Abstract]
    
    
19. Mecklenburg RE, Christen AG, et al.: How to Help Your Patients Stop Using Tobacco: a National Cancer Institute Manual for the Oral Health Team. Bethesda, Md: National Institutes of Health, National Cancer Institute, 1993. 
    
    
20. Martin LM, Bouquot JE, Wingo PA, et al.: Cancer prevention in the dental practice: oral cancer screening and tobacco cessation advice. J Public Health Dent 56 (6): 336-40, 1996 Fall.  [PUBMED Abstract]
    
    
21. Nelson NJ: "Big Smoke" has big risks: daily cigar use causes cancer, heart disease. J Natl Cancer Inst 90 (8): 562-4, 1998.  [PUBMED Abstract]
    
    
22. Firth NA: Marijuana use and oral cancer: a review. Oral Oncol 33 (6): 398-401, 1997.  [PUBMED Abstract]
    
    
23. La Vecchia C, Tavani A, Franceschi S, et al.: Epidemiology and prevention of oral cancer. Oral Oncol 33 (5): 302-12, 1997.  [PUBMED Abstract]
    
    
24. Bagnardi V, Blangiardo M, La Vecchia C, et al.: Alcohol consumption and the risk of cancer: a meta-analysis. Alcohol Res Health 25 (4): 263-70, 2001.  [PUBMED Abstract]
    
    
25. Gillison ML, D'Souza G, Westra W, et al.: Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst 100 (6): 407-20, 2008.  [PUBMED Abstract]
    
    
26. Winn DM, Ziegler RG, Pickle LW, et al.: Diet in the etiology of oral and pharyngeal cancer among women from the southern United States. Cancer Res 44 (3): 1216-22, 1984.  [PUBMED Abstract]
    
    
27. Winn DM: Diet and nutrition in the etiology of oral cancer. Am J Clin Nutr 61 (2): 437S-445S, 1995.  [PUBMED Abstract]
    
    
28. Horn-Ross PL, Morrow M, Ljung BM: Diet and the risk of salivary gland cancer. Am J Epidemiol 146 (2): 171-6, 1997.  [PUBMED Abstract]
    
    
29. Morse DE, Pendrys DG, Katz RV, et al.: Food group intake and the risk of oral epithelial dysplasia in a United States population. Cancer Causes Control 11 (8): 713-20, 2000.  [PUBMED Abstract]
    
    
30. Carley KW, Puttaiah R, Alvarez JO, et al.: Diet and oral premalignancy in female south Indian tobacco and betel chewers: a case-control study. Nutr Cancer 22 (1): 73-84, 1994.  [PUBMED Abstract]
    
    
31. Naylor MF, Farmer KC: The case for sunscreens. A review of their use in preventing actinic damage and neoplasia. Arch Dermatol 133 (9): 1146-54, 1997.  [PUBMED Abstract]
    
    
32. Cummings SR, Tripp MK, Herrmann NB: Approaches to the prevention and control of skin cancer. Cancer Metastasis Rev 16 (3-4): 309-27, 1997 Sep-Dec.  [PUBMED Abstract]
    
    
33. Chiesa F, Tradati N, Grigolato R, et al.: Randomized trial of fenretinide (4-HPR) to prevent recurrences, new localizations and carcinomas in patients operated on for oral leukoplakia: long-term results. Int J Cancer 115 (4): 625-9, 2005.  [PUBMED Abstract]
    
    
34. Halder A, Raychowdhury R, Ghosh A, et al.: Black tea (Camellia sinensis) as a chemopreventive agent in oral precancerous lesions. J Environ Pathol Toxicol Oncol 24 (2): 141-4, 2005.  [PUBMED Abstract]
    
    
35. Lin DT, Subbaramaiah K, Shah JP, et al.: Cyclooxygenase-2: a novel molecular target for the prevention and treatment of head and neck cancer. Head Neck 24 (8): 792-9, 2002.  [PUBMED Abstract]
    
    
36. Armstrong WB, Kennedy AR, Wan XS, et al.: Clinical modulation of oral leukoplakia and protease activity by Bowman-Birk inhibitor concentrate in a phase IIa chemoprevention trial. Clin Cancer Res 6 (12): 4684-91, 2000.  [PUBMED Abstract]
    
    

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Changes To This Summary (08/27/2008)

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.

Evidence of Benefit ¹²

Added Avoidance of HPV Infection ¹³ as a new subsection.

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