Mouthwash and Oral Cancer Risk Quantitative Meta-analysis of Epidemiologic Studies

Sara Gandini 1,  
Eva Negri 2, 3,  
Carlo La Vecchia 2, 3,  
Peter Boyle 2  
European Institute of Oncology, Milan, Italy; International Prevention Research Institute, Lyon, France
International Prevention Research Institute, Lyon, France
Istituto di Ricerche Farmacologiche Mario Negri , Milano, Italy
Ann Agric Environ Med 2012;19(2):173–180
Use of mouthwash and an increased risk of oral cancer has been a source of controversy for decades. A meta-analysis of epidemiological studies of mouthwash and oral cancer and, specifically, mouthwash containing >25% alcohol, was undertaken.

Summary estimates were obtained with maximum likelihood estimates from random effects models. Sensitivity analyses were conducted to evaluate the influence of various inclusion.

Eighteen studies were included in the meta-analysis. There was no statistically significant associations found between regular use of mouthwash and risk of oral cancer (RR=1.13; 95% CI (0.95-1.35)). There was no significant trend in risk of oral cancer associated with increased daily usage of mouthwash (p=0.11). There was no association between reported use of mouthwash specifically containing alcohol and risk of oral cancer (RR=1.16; 95% CI (0.44, 3.08)).

This quantitative analysis of mouthwash use and oral malignancy revealed no statistically significant associations between mouthwash use and risk of oral cancer, nor any significant trend in risk with increasing daily use; and no association between use of mouthwash containing alcohol and oral cancer risk.

Peter Boyle   
International Prevention Research Institute, Lyon, France
1. Boyle P and Levin B (eds). World Cancer Report 2008. IARC, Lyon, 2008.
2. Macfarlane GJ, Boyle P, Evstifeeva TV, Robertson C, Scully C. Rising Trends of Oral Cancer Mortality World-wide, The return of an old Public Health Problem. Cancer Causes and Control. 1994; 5: 259-265.
3. Boyle P, Smans M. Cancer Mortality Atlas of European Union, 1993-1997. IARC Press, IARC ,Lyon; 2008.
4. Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M, Boyle P. (eds). Cancer Incidence in Five Continents. IARC Scientific Publications 2007; IX(160).
5. International Agency for Research on Cancer Working Party. Eversal of Risk after quitting smoking. IARC Handbooks of Cancer Prevention, Tobacco Control, Volume 11, IARC, Lyon; 2006.
6. Sapkota A, Gajalakshmi V, Jetly DH, et al. Smokeless tobacco and increased risk of hypopharyngeal and laryngeal cancers: a multicentric case-control study from India. Int J Cancer. 2007; 121: 1793-1798.
7. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 85. Betel-quid and Areca-nut Chewing and Some Areca-nut derived Nitrosamines. IARC, Lyon; 2006.
8. Secretan B, Straif K, Baan R, Grosse Y, El Ghissassi F, Bouvard V, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, Cogliano V. WHO International Agency for Research on Cancer Monograph Working Group. A review of human carcinogens--Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol. 2009; 10(11): 1033-4.
9. Zheng T, Boyle P, Hu J, Duan P, Jiang D, Ma L, Shui L, Niu S, Scully C, MacMahon B. Dentition, oral hygiene and risk of oral cancer: a case-control study in Beijing, People’s Republic of China. Cancer Causes and Control 1990; 1: 235-242.
10. Kreimer AR, Clifford GM, Boyle P and Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol. Biomarkers Prev. 2005; 14(2): 467-75.
11. Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Bouvard V, Altieri A, Cogliano V. WHO International Agency for Research on Cancer Monograph Working Group. Carcinogenicity of alcoholic beverages. Lancet Oncol. 2007; 8(4): 292-3.
12. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283(15): 2008-12.
13. Greenland S. Quantitative methods in the review of epidemiologic literature. Epidemiol Rev. 1987; 9: 1-30.
14. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21(11): 1539-58.
15. van Houwelingen HC, Arends LR and Stijnen T. Advanced methods in meta-analysis: multivariate approach and meta-regression. Stat Med. 2002; 21(4): 589-624.
16. Greenland S, Longnecker MP. Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol. 1992; 135(11): 1301-9.
17. Macaskill P, Walter SD and Irwig L. A comparison of methods to detect publication bias in meta-analysis. Stat Med. 2001; 20(4): 641-54.
18. Marques L, Eluf-Neto J, Figueiredo ROA, Góis-Filho JF, Kowalski LP, de Carvalho MB, Abrahão M, Wünsch-Filho V. Oral health, hygiene practices and oral cancer. Rev Saúde Pública 2008; 43: 471-9.
19. Fernandez Garrote L, Herrero R, Ortiz Reyes RM, Vaccarella S, Lence Anta K, Ferbeye L, Muñoz N, Franceschi S. Risk factors for cancer of the oral cavity and oro-pharynx in Cuba. Brit J Cancer 2001; 85: 46-54.
20. Winn DM, Blot WJ, McLaughlin JK, Austin DF, Greenberg RS, Preston-Martin S, et al. Mouthwash use and oral conditions in the risk of oral and pharyngeal cancer. Cancer Res. 1991; 51: 3044-7.
21. Winn DM, Diehl SR, Brown LM, Harty LC, Bravo-Otero E, Fraumeni Jr JF, et al. Mouthwash in the etiology of oral cancer in Puerto Rico. Cancer Causes Control 2001; 12: 419-29.
22. Divaris K, Olshan AF, Smith J, Bell ME, Weissler MC, Funkhouser WK, Bradshaw PT. Oral health and risk for head and neck squamous cell carcinoma: the Carolina Head and Neck Cancer Study. Cancer Causes Control 2010; 21: 567-75.
23. Macfarlane TV, Macfarlane GJ, Oliver RJ, Benhamou S, Bouchardy C, Ahrens W, Pohlabeln H, Lagiou P, Lagiou A, Castellsague X, Agudo A, Merletti F, Richiardi L, Kjaerheim K, Slamova A, Schejbalova M, Canova C, Simonato L, Talamini R, Barzan L, Conway DI, McKinney PA, Znaor A, Lowry RJ, Thomson P , Healy CM, McCartan BE, Marron M, Hashibe M, and Brennan P. The aetiology of upper aerodigestive tract cancers among young adults in Europe: the ARCAGE study. Cancer Causes Control. 2010; 21: 2213-21.
24. La Vecchia C, Tavani A, Franceschi S, Levi F, Corrao G, Negri E. Epidemiology and prevention of oral cancer. Oral Oncol. 1997; 33: 302-12.
25. Guha N, Boffetta P, Wunsch Filho V, Eluf Neto J, Shangina O, Zaridze D, et al. Oral health and risk of squamous cell carcinoma of the head and neck and esophagus: results of two multicentric case–control studies. Am J Epidemiol. 2007; 166: 1159-73.
26. Blot WJ, Winn DM, Fraumeni Jr JF. Oral cancer and mouthwash. J Natl Cancer Inst. 1983; 70: 251-3.
27. Wynder EL, Kabat G, Rosenberg S, Levenstein M. Oral cancer and mouthwash use. J Natl Cancer Inst. 1983; 70: 255-60.
28. Young TB, Ford CN, Brandenburg JH. An epidemiologic study of oral cancer in a statewide network. Am J Otolaryngol. 1986; 7: 200-8.
29. Mashberg A, Barsa P, Grossman ML. A study of the relationship between mouthwash use and oral and pharyngeal cancer. J Am Dent Assoc. 1985; 110: 731-4.
30. Kabat GC, Hebert JR, Wynder EL. Risk factors for oral cancer in women. Cancer Res. 1989; 49: 2803-6.
31. D’Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, et al. Case–control study of human papillomavirus and oropharyngeal cancer. New Engl J Med. 2007; 356: 1944-56.
32. Weaver A, Fleming SM, Smith DB. Mouthwash and oral cancer: carcinogen or coincidence? J Oral Surg. 1979; 37: 250-3.
33. Mascarenhas AK, Allen CM and Moeschberger ML. The association between Viadent use and oral leukoplakia--results of a matched case-control study. J Publ Health Dent. 2002; 62: 158-62.
34. Morse D, Katz R, Pendrys D, et al. Mouthwash use and dentures in relation to oral epithelial dysplasia. Oral Oncol. 1997; 33: 338-43.
35. Marshall JR, Graham S, Haughey BP, Shedd D, O’Shea R, Brasure J, et al. Smoking, alcohol, dentition and diet in the epidemiology of oral cancer. Eur J Cancer B Oral Oncol. 1992; 28B: 9-15.
36. Elmore JG, Horwitz RI. Oral cancer and mouthwash use: evaluation of the epidemiologic evidence. Otolaryngol Head Neck Surg. 1995; 113: 253-61.
37. Shapiro S, Castellana JV, Sprafka JM. Alcohol-containing mouthwashes and oropharyngeal cancer: a spurious association due to under-ascertainment of confounders? Am J Epidemiol. 1996; 144: 1091-5.
38. Cole P, Rodu B, Mathisen A. Alcohol-containing mouthwash and oropharyngeal cancer: a review of the epidemiology. J Am Dent Assoc. 2003; 134: 1079-87.