Current thinking about the effects of e-cigarettes on oral cancer risk

Electronic nicotine delivery systems (ENDS) include electronic cigarettes (e-cigarettes), electronic vaporisers and vape pens. There has been an exponential rise in e-cigarette use (‘vaping') since they became available in the UK in 2005.¹ This number is only likely to increase following recent national news headlines outlining that one million smokers in the UK will be given a free vaping starter kit to encourage them to give up tobacco products.² An independent review by Dr Javed Khan OBE into the government's ambition to make England smoke-free by 2030 promotes vaping as an alternative, while concomitantly recognising that ENDS are neither a ‘silver bullet' nor ‘totally risk free'.³

Undoubtedly, the dental team will now encounter many more questions from patients keen to know more regarding the safety of ENDS and their effects on the oral cavity. The paucity of evidence regarding their potential detrimental effects to both oral health and systemic health makes these questions difficult to answer; however, it is now well-accepted that these are a safer alternative to conventional cigarette smoking.⁴ We aim to summarise the current evidence on the risks of vaping on oral health, with particular focus on oral cancer risk, to better inform the dental team, enabling them to better inform their patients (Table 1).

PubMed was used to search for applicable papers using the search terms: e-cigarettes; ENDS; vaping; oral cancer; oral health. Papers included were those written in English language and no end date was specified. The most recent papers were selected based on determining suitability from their abstract.

ENDS were introduced as a safer alternative to conventional smoking. They are popular among conventional smokers and also with previously non-smoker adolescents, some of whom are attracted to the content of flavourings.⁵ ENDS comprise of a battery-powered heating element to aerosolise a liquid, which is subsequently inhaled. The liquid contents usually include nicotine, flavouring agents and propylene glycol and/or glycerine. Nicotine-free forms are also available.⁶ Further analysis has often identified tobacco alkaloids, formaldehyde, glycerol and heavy metals, but it is important to note that there is a large variation in nicotine and toxic content delivery between brands of ENDS. Second-hand exposure of non-users via the generated aerosol and exhaled vape occurs, but it is currently unclear if this poses a meaningful biological risk.^4,7

A [recent] review has outlined the effects of ENDS exposure on oral health, including dysbiosis and changes to the oral microbiome

The first contact of the inhaled e-aerosol occurs in the oral cavity; data on the effects of this interaction come mainly from animal or in vitro studies and is, at present, generally low-quality.⁸ A recently published review has outlined the effects of ENDS exposure on oral health, including dysbiosis and changes to the oral microbiome, with evidence of a compositional and functional shift in the oral microbiome and an increase in opportunistic pathogens.^9,10 ENDS use was also implicated in adverse effects on the head, neck, oral cells regarding aberrant morphology, cytotoxicity, reduced viability, delayed fibroblast migration and genotoxicity; however, most articles in this systematic review found conventional cigarette smoke to be significantly more toxic to head, neck and oral cells than that of ENDS.¹

The popularity of ENDS is, in part, likely to be due to their appeal as a safer alternative to conventional cigarettes.¹¹ The literature broadly agrees with this, recognising ENDS are a much safer alternative. The headline results from the recent Action on Smoking and Health survey found that, in March/April 2023, the proportion of children experimenting with vaping had grown by 50% year on year, from 1 in 13 to 1 in 9.¹² Other reasons for children vaping are cited as liking the flavours and because their peers do it. More than half of never-smokers reported ENDS use ‘just to give it a try' compared to one-quarter of those who have ever smoked historically.¹²

ENDS are recognised as a safer alternative to conventional cigarettes due to the lower content of toxic and carcinogenic compounds.⁶ While the role of conventional cigarette smoking in oral cancer development is well-known, the role of ENDS in oral cancer and systemic disease is less clear. In part, this is due to difficulties in establishing reliable toxicity profiles of ENDS because of variations in design, manufacturing and ingredients.^4,8 E-cigarettes have fewer carcinogens than cigarettes, in substantially lower amounts, but the same basic mechanism of DNA damage may apply.⁸ However, the risk of developing head and neck squamous cell carcinoma remains lower in users of ENDS compared with conventional tobacco smokers.⁶

Although the heavy metal constituents in ENDS are presently at much lower levels than in conventional cigarettes, it is understood that chronic exposure to heavy metals via tobacco smoking increases the risk of head and neck cancer.⁶ Formaldehyde and acetaldehyde have often been reported as common constituents in ENDS.^1,6,13 One study evaluated 225 ENDS fluids and found both chemicals to be present in all fluids.¹⁴ Formaldehyde is a recognised Group 1 human carcinogen, posing nasopharyngeal cancer risk.⁶

The quality of the evidence regarding oncogenic effects is poor.⁵ In vitro studies have widely demonstrated that e-cigarette liquid or vapour can induce DNA damage, oxidative stress, DNA double-stranded breaks, apoptosis, necrosis and genotoxicity in different types of oral cells.^1,5 Further in vitro studies have demonstrated the ability of ENDS e-liquids to induce changes contributing to the development of tumorigenesis in normal epithelial cells and promote aggressive phenotypes in pre-existing malignant cells.¹⁵ However, the lack of long-term prospective and large-scale case-control studies is a major limiting factor in determining the association of ENDS with oral cancer progression. Although the presence of carcinogenic agents in ENDS liquid and vapour has been shown to induce DNA strand breaks and gene alteration, it is important to note there is not sufficient evidence to infer a causal relationship. To the authors' knowledge, the evidence only comprises of case reports of oral cavity cancer in patients with heavy e-cigarettes usage, who are otherwise not exposed to other conventional risk factors.¹³

The deleterious effects of tobacco smoking are numerous and well-established.⁵ In the absence of tobacco smoke, the effect of the long-term use of nicotine on cancer risk is not clearly understood.⁶ A 2019 randomised control trial found no adverse events related to either nicotine replacement therapy (NRT) or ENDS but did find that NRT users were more likely to report nausea (37.9% versus 31.3% of ENDS users) while ENDS users were more likely to report mouth or throat irritation (65.3% versus 51.2% of NRT users). This study did find that ENDS are substantially more effective than NRT at helping conventional smokers quit.¹⁶

One study has suggested that, like combustible tobacco, ENDS use might increase chemotherapy resistance.¹⁷ E-cigarette use has demonstrable association with a decreased expression of immune-related genes which offers a potential mechanism to support the association between ENDS use and oral HPV-16 (human papillomavirus) infection.¹⁸ Other studies suggest that ENDS pose indirect health risks by increasing likelihood of future tobacco smoking among adolescent ENDS users.¹⁹

Commonly reported oral symptoms include xerostomia, burning, pain, oral ulceration, nicotine stomatitis, hairy tongue and angular cheilitis

Poor-quality evidence exists with regard to oral symptoms pertaining to ENDS, usually because the data are self-reported.⁵ In the literature, commonly reported oral symptoms related to e-cigarette use include xerostomia, burning sensation, irritation, pain, oral ulceration, nicotine stomatitis, hairy tongue and angular cheilitis.^1,4,5 Accidents with ENDS have also been reported; burns of various degrees as a result of e-cigarette explosions and malfunctions have resulted in oral cavity injury.⁹

It is important to note that ENDS differ significantly in terms of their voltage and liquid contents, so it is likely that deleterious oral health effects vary between products⁴ and disease occurrence or progression is likely to be related to the dose and individual product. When patients report ENDS use, it is important that clinicians document this as part of a holistic assessment of oral cavity cancer risks as they would do with tobacco smoking. Clinicians may counsel patients that the evidence base regarding ENDS safety is weak and we are not yet aware of the full risk profile of these products, but current evidence suggests they are safer than conventional smoking for current smokers but are not recommended for those who are currently non-smokers. Obtaining a patient's smoking status is the first step in the delivery of smoking cessation counselling.

Typically, questions relating to smoking status are included on patient medical health questionnaires or confirmed verbally during consultations. Smoking status is usually recorded in pack years: a means of quantifying the amount a person has smoked over time.²⁰ To date, documentation of ENDS has been less systematic than that of conventional smoking.²¹ We advocate the implementation of a simple tool (Table 2) adapted from that developed by Jose et al.²² to help clinicians capture meaningful and complete data relating to ENDS use. This can stratify individual oral health risk factors and provide tailored cessation advice. We recommend that cigarette smoking status is expanded to routinely include ENDS status.

It is likely that deleterious oral health effects vary between ENDS products.⁴ When patients report ENDS use, dental care practitioners could advise that, according to current evidence, these devices appear to be considerably less harmful than conventional smoking but still cannot be considered entirely ‘safe' as there are some risks associated. The authors propose that ENDS consumption should be documented systematically (Table 2). All studies reviewed concluded there is a need for extensive research to better assess the effects of ENDS use on oral cavity tissues.

This article was originally published in the BDJ on 8 March 2024; Volume 236 pages 397-400.