Introduction
Alcohol abuse is frequently included in the list of risk factors for the development of cancer in the upper alimentary tract. In view of this association, there has been concern in recent years in relation to the use of alcohol-containing mouthwashes and the possibility of an increased incidence of oral cancer. One survey has revealed that 16% of dental hygienists and 7% of dental practitioners do not recommend the use of an alcohol-containing mouthwash due to a concern about safety1.
Alcohol is frequently included as a constituent of mouthwashes, such as Corsodyl, Peroxyl, Listerine and Plax, either as a solvent for other ingredients or as a preservative. In view of the evidence base supporting the positive benefit of some mouthwashes in oral care, it would seem appropriate to examine the evidence in the scientific literature to determine if there is a true link between the inclusion of alcohol in mouthwashes, their use and an increased risk of oral cancer. Firstly, is there information that alcohol itself is a carcinogen or that it has effects on the oral mucosa? Secondly, what clinical evidence is there in relation to the incidence of oral cancer in individuals who use alcohol-containing mouthwashes and those who do not use such products?
Alcohol
Whilst alcohol abuse has long been associated with oral cancer, pure ethanol has never been shown to be carcinogenic either in vivo or in vitro. Determining the exact role of alcohol consumption and aetiology of oral cancer is complicated by several factors. The most frequently cited reason for lack of definitive evidence on a carcinogenic capacity of alcohol is a difficulty in separating the effects of heavy consumption of alcohol from those of smoking since most individuals who have high intake of alcohol also have substantial tobacco use. Despite these problems, there is increasing evidence that the carcinogenic potential of alcoholic drinks is due to the presence of contaminants or congeners rather than the alcohol itself.
Different types of alcoholic drinks have been found to contain a number of recognised carcinogens including nitrosamines, polycyclic hydrocarbons, fusel oil and aflatoxins. It is believed that the presence of these substances explains the high incidence of oral cancer in certain regions in France and Puerto Rico, where there is a high intake of locally prepared ‘home distilled’ alcoholic drinks. There has been specific attention to the presence of dimethylnitrosamine (DMN) and diethlynitrosamine (DEN) in apple cider and brandy made in Normandy, France. Studies on the consumption of these preparations have revealed an increased risk of oral cancer. This observation has implicated the alternative substances as the carcinogens rather than the alcohol itself. This association is further supported by the fact that there is no experimental evidence to indicate that ethanol is carcinogenic.
A number of mechanisms have been investigated to determine the potential role of alcohol in the aetiology of oral cancer. As mentioned above, there is a potential for other carcinogens to be present in alcoholic drinks. However, investigators have also looked at either the direct effect of ethanol on epithelial cells or the secondary changes within the epithelium due to systemic effects of alcohol on the liver. Alcohol-containing mouthwashes are not swallowed and therefore any potential effect on the oral mucosa would have to be mediated by a direct local action rather than by any systemic effect. It is generally recognised that ethanol can influence the permeability of skin and therefore it may have a similar action on permeability of the oral mucosa. Indeed it has been shown that the permeability of the oral mucosa is increased in relation to a tobacco-associated carcinogen nitrosonornicotine in the presence of ethanol after one hour. However, this in vitro model, in addition to involving extended periods of exposure, does not account for in vivo factors such as the presence of salivary mucin and salivary flow, both of which would modify any effect on the permeability of the mucosa.
Specific evaluation of the essential oils based mouthwash Listerine, which contains up to 26.9% alcohol, on the permeability of oral mucosa under conditions resembling actual usage concluded that the use of such a mouthwash is unlikely to alter the permeability barrier properties of the oral mucosa to water soluble compounds.
In summary therefore, at the present time, laboratory-based research investigating ethanol indicates that it is neither a carcinogen nor does it adversely effect the permeability of the oral tissues when used as a constituent of mouthwashes.
Clinical studies
During the past 25 years, eight epidemiological studies have been undertaken to determine if the use of alcohol-containing mouthwashes was associated with an increased incidence of oropharyngeal cancer.
Blot et al (1983) used a questionnaire to determine patterns of mouthwash use in 206 women with oral and pharyngeal cancer. This controlled study, with adjustment for tobacco habits, concluded there was no significant increase in the risk of oral cancer. Mashberg et al (1985) looked at a veteran male population with oral cancer and found no significant difference in the incidence of oral or pharyngeal cancer in patients who used or did not use mouthwashes. In this particular study there was no evidence that a mouthwash should be considered as a risk factor for the development of oral and pharyngeal cancer in males.
An epidemiological study of sufferers of oral cancer in the state of Wisconsin, USA, examined data from more than 600 individuals and concluded that mouthwash use was not found to carry a risk of oral cancer, pharyngeal cancer or hypopharyngeal cancer.
Kabat et al (1989) interviewed 125 women with oral cancer and investigated the role of mouthwash use. In this particular controlled study, mouthwash use was not associated with increased oral cancer in relation to frequency, duration of use, dilution or rinsing practice8. Research by Morse et al (1997) explored the presence of oropharyngeal epithelial dysplasia, a potential indicator for the development of oral malignancy, and mouthwash or denture use. It was concluded that there were no trends for increased incidence of dysplasia in association with increased mouthwash use.
A case control study by Wynder et al (1983) evaluated the relationship between mouthrinses and oropharyngeal cancer, reported a possible increased risk in women; however smoking and alcohol beverage consumption had not been accounted for. A detailed multiple logistic modelling to take account of these confounding factors resulted in no association of mouthwash use and oral cancer amongst women.
More recently, Winn et al 2001 undertook a study investigating potential aetiological factors in oral cancer in Puerto Rico, a locality with a high incidence of oral cancer. This study also found no overall increased risk of oral cancer associated with alcohol mouthwash use11. An elevated but not statistically significant risk was observed in women who neither smoked tobacco nor drank alcohol. In an early study by Weaver et al, involving 200 patients with squamous cell carcinoma of the head and neck, there was a suggestion that alcohol mouthwash use should be recorded in patients with premalignant or malignant lesions of the oral cavity. This conclusion was based on the fact that 10 patients from the 200 subject had used a mouthwash but had abstained from alcohol beverages and tobacco. There was no statistically significant association and the subsequent studies outlined above have not supported this early observation.
A review article examining the methodology employed in these epidemiological studies acknowledged the difficulty of undertaking such investigation due to the confounding factors of tobacco and alcohol use13. However, the review concluded that the available evidence did not support a causal association between mouthwash use and the development of oral cancer.
The FDA have investigated the relationship between alcohol-containing mouthwashes and oral cancer on two occasions, firstly in 1996 and most recently in 200315. On both occasions the FDA concluded that there was no evidence in the available literature to support a causal relationship of mouthwash use and oral cancer.
Summary
The present review of the published literature has revealed that topical alcohol in mouthwashes itself is not associated with either the development of oral cancer or an adverse effect on the permeability of the oral mucosa. This conclusion supports Cole et al (2003) who also previously reported that the epidemiological literature, published during the past 25 years, in relation to the development of oral cancer in populations who use alcohol-containing mouthwashes, does not show an increased incidence of oral cancer in such patients16. Alcohol-containing mouthwashes have been shown to be beneficial as a component of maintaining oral health. It is concluded therefore that dental professionals should not be dissuaded from recommending alcohol-containing mouthwashes to their patients on the basis of a fear of developing oral cancer. The scientific literature shows that such an association is unfounded.
