Alcohol-Containing Mouthwash and the Risk of Oral Cancer: Exploring the Association

Abstract

Oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse or both. Mouthwashes are liquid antiseptic solutions that decrease the microbial load in the oral cavity. Alcohol is often used in mouthwashes for its antiseptic functions and as a carrier for some active ingredients, including menthol or thymol, helping them penetrate the plaque. There is some evidence for alcohol-containing mouthwash use which is associated with the potential risk of developing carcinoma of oral cavity. The results are inconclusive, as actual mouthwash use patterns may be inconsistent and cannot be easily quantified. Based on the available data, there is no sufficient evidence to accept the proposition that the use of mouthwashes containing alcohol can influence the development of oral cancer.

Introduction

Squamous cell carcinoma (SCC) of the head and neck is one of the most common tumour types, causing significant morbidity and mortality [1]. Cancers of the oral cavity and larynx are commonly linked to tobacco usage, alcohol addiction, or both. Mouthwashes are liquid antiseptic solutions that lower the concentration of pathogens in the oral cavity. There are formulations for analgesic, anti-inflammatory, anti-fibrinolytic, antifungal, or aesthetic reasons. Alcohol is frequently used in mouthwashes with concentrations ranging from 5 to 27% [2] for its antimicrobial effects and as a carrier for some active chemicals, such as menthol, allowing them to penetrate the plaque. This report aimed to explore the literature and to determine if alcohol-containing mouthwash use is associated with the potential risk of developing SCC of the oral cavity.

Contention for Alcohol in Mouthwashes

Weaver et al. investigated the likelihood of high alcohol-containing mouthwashes contributing to oral cancer more than 50 years ago. Ten patients in their 200-person cohort with head and neck squamous cell carcinoma had used mouthwash frequently for more than 20 years; the mouthwash used was commercial formulations containing 27% alcohol [3].

In cross-sectional research, Bolt et al. explored the patterns of mouthwash use among women in the Western USA. They reported that the relative risk linked with mouthwash use was 1.94 (95% confidence interval (CI) = 0.8, 4.7) among women who did not smoke. They could not establish a consistent dose–response relationship for this subgroup, and they concluded that their findings of an increased risk of disease raise the idea that mouthwash may contribute to oral and pharyngeal malignancies [4].

In 1983, Wynder et al. conducted a retrospective analysis that included 71 cases and matched them with 6047 control subjects. This study found that using mouthwash daily was linked with an elevated risk among females, regardless of alcohol or tobacco usage. Nonetheless, the hazards were minor, and there was no dose–response association. The investigation revealed the significant dangers connected with alcohol consumption and cigarette use. Because of confounding by these far more influential factors, these scientists concluded that no causal relationship for mouthwash use could be deduced [5].

Winn et al. conducted interviews with 866 patients with oral cavity and pharyngeal cancer and 1249 controls of comparable age and sex from the USA population; the findings demonstrated elevated risks linked with the regular use of mouthwash. After accounting for tobacco and alcohol use, the dangers of oral cancer increased by 40% among male and 60% among female mouthwash users. The risks increased in proportion to the frequency and duration of mouthwash usage. They were only visible when the alcohol level of the mouthwash exceeded 25%—the effects were more significant in women, with a maximum odds ratio (OR) of 2.4 (1.5–3.9) in those who began frequent use before the age of 20 [6]. Johnson and colleagues voiced their concern as smokers are prone to use alcohol-containing mouthwashes heavily to cover up the smell of tobacco. ORs rarely reach 2 in most reported research, including 95% CIs [7].

Winn et al. interviewed 521 population-based controls about mouthwash use and other characteristics in 2001, along with 342 oral and pharyngeal cancer registered in Puerto Rico. Use of mouthwash with a 25% alcohol level or more was related to a 1.0 adjusted OR. The odds ratio associated with mouthwash use was 2.8 (0.8–9.9) among those who did not use cigarettes or alcohol, as opposed to 0.8 (0.4–1.7) and 0.9 (0.6–1.3), respectively, among those who did. They concluded that using mouthwash did not generally raise the chance of developing oral cancer. The small group of patients who neither smoked cigarettes nor drank alcohol but whose effects from alcohol-containing mouthwash would most likely be noticeable had an enhanced risk that was not statistically significant [8].

In a meta-analysis on mouthwash use and oral cancer, eighteen articles were included in a meta-analysis carried out by Gandini et al. in 2012. Regular mouthwash use was not linked, statistically speaking, to an increased risk of oral cancer (Relative risk (RR) = 1.13 (0.95–1.35)). The reported use of alcohol-specific mouthwash was not associated with an increased risk of oral cancer (RR = 1.16 (0.44, 3.08)) [9].

In the analysis of this meta-analysis, Lachenmeier argued that there might be too much confounding from smoking and alcohol use for extensive research and advanced statistics to identify a negligible danger posed by alcohol-containing mouthwashes [10].

Boffetta et al. from the International Head and Neck Cancer Epidemiology Consortium (INHANCE) performed a pooled analysis of 8981 cases of head and neck cancers (HNC) with 10,090 controls from twelve published case–control studies with comparable information on mouthwash use. There were 1167 oral cavity cancer cases in the subset and 4288 exposed controls. There was no higher risk for HNC overall when mouthwash was used compared to never using it, but there was a slightly higher risk for two subsites: the oral cavity (OR = 1.11 (1.00–1.23)) and the oropharynx (OR = 1.28 (1.06–1.56)). There was a small measured association between long-term mouthwash use (> 35 years) and HNC (OR = 1.15, (1.01–1.30)), which was comparable to those who used mouthwash more than once a day for more than 35 years (OR = 1.31 (1.09–1.58)) and more than twice a day for more than 35 years (OR = 1.75 (1.25–2.48)). These ORs were modified for age, gender, education level, and cigarette and alcohol use. The authors acknowledged that separating mouthwash use from heavy drinking and smoking was challenging [11].

Hypothesis for carcinogenesis

In 2014, Currie et al. reviewed fifteen case–control studies, of which nine revealed evidences in favour of and six in opposition to a relationship between mouthwash use and the development of SCC. They also included eleven evaluations examining the supporting data for these correlations. The authors made the supposition that is using mouthwash with alcohol.

• Reduces the role that oral flora plays in salivary acetaldehyde production. Acetaldehyde, the primary derivative of ethanol metabolism, plays a significant role. Its noteworthiness arises from its toxic, mutagenic, and carcinogenic attributes, primarily its capacity to bind to DNA and generate carcinogenic adducts. This underscores its crucial contribution to this intricate process [12]. However, those who use such a product temporarily exhibit higher amounts of the salivary acetaldehyde (nearly 0.26 µg/kg body weight (2)) than people who use non-alcoholic mouthwash.

• Increases the vulnerability of oral mucosa to carcinogens from tobacco smoke and may trigger cytochrome P450 2E1, which is a possible step in the development of cancer.

• To get rid of the tobacco smoke odour from their mouths, smokers are more likely than non-smokers to use mouthwash.

  • ⚬ Due to tobacco usage, mouthwash users who smoke have a higher chance of developing oral cancer than those who do not smoke.

• An oral lesion may prompt someone to use mouthwash, exacerbating the condition, and making it more severe.

They concluded that there needs to be more agreement among studies about whether alcohol-containing mouthwash and the emergence of oral squamous cell carcinoma are related. They suggested this was caused mainly by subpar epidemiological study design, a lack of comparability, and scant research on mechanical components in vivo and in vitro. They recommended that practitioners encourage non-alcoholic mouthwashes and discourage the long-term use of those that contain high quantities of alcohol before any firm conclusions can be made [13].

Hashim et al. [14] cautioned that mouthwash use is not essential to good oral hygiene, while daily tooth brushing (fluoridated toothpaste) is. On the contrary, some people believe that using mouthwash once or twice a day can safely help maintain dental plaque volumes below unsafe levelzs [15].

The Results from the Systematic Review and Meta-analyses

The most recent meta-analysis, conducted in 2022 by Carr et al. from Scotland, found a complex interaction between the usage of alcohol mouthwash and the chance of developing cancer. Increased rinsing (more than three times per day), total mouthwash use (over 35 years), poor oral hygiene, and the existence of additional risk factors are variables that may affect the chance of getting oral cancer from using alcohol mouthwash (for example, smoking, and alcohol intake) [16].

Hostiuc et al. from Romania conducted a meta-analysis in 2021 that comprised 17 studies, 17,085 cases, and 20,032 controls. With a value of − 0.02 (− 0.05, 0.01), the risk difference for HNC between mouthwash users and non-users was negligibly slight. Alcoholic mouthwash was linked to a negligible reduction in risk of − 0.01 (− 0.07, 0.05). A statistically significant risk increase for HNC was related to frequent mouthwash use, but the risk increase was slight (0.04, (0.01, 0.06)). Three thousand eight hundred thirty-three oral cancer participants, of whom 1475 used mouthwash and 13,018 controls—of whom 5194 used mouthwashes made up the oral cancer subset. At 0.02 (− 0.02, 0.05), the risk difference between the cases and control groups was negligible and not statistically significant. According to their research, no statistically proven link exists between using mouthwash and the likelihood of developing HNC. They only found one statistically significant association between frequent use and head and neck SCC [17].

Ustrell-Borras et al. reviewed in 2020; eight research totalling 43,499 people were included in their qualitative analysis. Three studies with 14,482 patients failed to find a connection between alcohol mouthwash and oral cancer, two studies with 58 patients discovered a transient increase in acetaldehyde levels in saliva after alcohol mouthwash, and one study with 3926 found a connection between alcohol mouthwash and oral cancer when a high frequency of mouth washing was present. They believed that mouthwash use is a separate risk factor for head and neck cancer. However, when it occurs with other carcinogenic risk factors, the risk rises [18].

In 2020, fourteen publications were included in a review by Argemi et al. Eight other case–control studies discovered statistically significant evidence, while three found no statistically significant evidence linking mouthwash use and oral cancer. Due to alcohol’s genotoxicity and mutagenic potential in prolonged contact with oral tissues and mucous membranes, the three clinical trials found a link between using mouthwashes with alcohol and the risk of acquiring cancer. The meta-analysis produced OR of 1.480 for the analysis of studies examining the relationship between mouthwash use and the risk of cancer, and OR of 1.057 for studies examining the relationship between mouthwash use and the risk of cancer without taking alcohol into account [19].

Conclusion

The observations are very tenuous since actual mouthwash usage patterns can be highly variable because people use different brands with different alcohol contents and diverse temporal consumption tendencies that are difficult to quantify. Prospective studies with rigorously controlled variables could produce better data; however, such studies are challenging and require a longer time horizon to identify pertinent trends correctly. According to the data available, there is limited support for the hypothesis that using mouthwashes containing alcohol can affect the occurrence of oral cancer. Nevertheless, regular use of broad-spectrum antiseptics damages the oral flora and any potential pathogens present. In any case, it seems prudent to keep the alcohol content as low as possible in formulating the product, as alcohol is necessary to dissolve some active antimicrobial agents and state the composition on the label.

Declarations

Competing Interests

The authors declare no competing interests.

Provenance and Peer Review

Not commissioned, externally peer-reviewed.