Received: 1 December 2018 | Accepted: 2 December 2018

DOI: 10.1111/jop.12810

SPECIAL ISSUE ARTICLE

Electronic nicotine delivery systems: Oral health implications

and oral cancer risk

Ahmed S. Sultan1 | Maryam Jessri2 | Camile S. Farah2

1
Department of Oncology and Diagnostic
Sciences, School of Dentistry, University of
There is a paucity of evidence surrounding the potential detrimental effects of elec-
Maryland, Baltimore, Maryland tronic nicotine delivery systems (ENDS) for both systemic and oral health. The
2
Australian Centre for Oral Oncology effects of conventional cigarettes on the development of oral cancer are well
Research & Education, UWA Dental School,
University of Western Australia, Nedlands, known; however, the role of ENDS in oral carcinogenesis is yet to be elucidated.
Western Australia, Australia Furthermore, the exponential rise of the use of ENDS by the general public means
Correspondence that dental healthcare providers are more likely to encounter questions on their
Ahmed S. Sultan, Department of Oncology safety in the oral cavity, and on their effectiveness as a smoking cessation aid.
and Diagnostic Sciences, School of
Dentistry, University of Maryland, Baltimore, Herein, we review the most up to date literature on the systemic and oral health
MD. complications of ENDS. Moreover, evidence‐based recommendations on the use of
Email: asultan@umaryland.edu
ENDS as a smoking cessation tool within the dental setting are discussed.

1 | INTRODUCTION Regardless of the generation or class, when an ENDS user vapes

Electronic nicotine delivery systems (ENDS) were first introduced in
the mid to late 2000s as a means to tobacco harm reduction.1 ENDS
are battery‐powered devices that aerosolize a solution (e‐liquid) con-
taining nicotine, flavouring chemicals, propylene glycol and glycerol
for the purpose of inhalation by the user. There are approximately
500 different brands of ENDS, and there exists a marked variability
in ENDS terminology, active chemicals, product design and engineer-
ing which results in significant differences in nicotine delivery mech-
2
anisms and more importantly toxin contents.
First‐generation or “cigalike” ENDS closely resemble traditional
cigarettes and comprise a low‐capacity or rechargeable battery, a
cartridge containing e‐liquid, and an atomizer which aerosolizes the
e‐liquid through heating.3 Second‐generation electronic cigarettes (e‐
cigarettes), or tank‐style systems, work through a similar mechanism.
These systems resemble a pen, include larger batteries and have
refillable fluid reservoirs (tank system).4 Compared to cigalike ENDS,
the tank system devices provide a wider variety of nicotine concentra-
tion and more efficient nicotine delivery, have more flavours to choose
from and are used by more experienced users. Third‐generation
devices, or advanced personal vaporizers, have higher nicotine delivery
potential and can mimic the profile of conventional combustible cigar-
5
ettes. Alternatively, depending on the degree of control that users
have over the voltage, resistance and the e‐liquid used, ENDS can be
classified as either open or closed systems.
(draws a breath from the device), the change in pressure activates
the aerosol generator and extracts the e‐liquid from the storage area,
which in turn results in production of an aerosol through heating or
mechanical dispersion of the e‐liquid. The generated aerosol will be
inhaled and subsequently exhaled by the user, resulting in second‐
hand exposure of nonusers through both the generated aerosol and
the exhaled vape. Systemic and oral health risks of ENDS are dis-
cussed in the following sections; however, it is currently unclear if
second‐hand exposure poses a meaningful biological risk to humans,
and further investigation is warranted prior to drawing a definitive
conclusion.6
In 2014, the Food and Drug Administration (FDA) issued a
draft regulation regarding the sale and use of ENDS, subjecting
them to regulations akin to that of tobacco products.7 As such, it
is perceived that ENDS are governed under tobacco regulations
and their sale to minors (<18 years of age) is prohibited.7 This
regulation however only pertains to the nicotine containing e‐
liquids and does not prohibit the sale of the device without nico-
tine to minors. Consequently, this potential loophole has raised
the understandable concern of minors purchasing non‐nicotine
containing e‐liquids or obtaining the e‐liquid from other sources
such as friends or family.7 This is a significant consideration given
that despite the steady decline in the use of conventional com-
bustible tobacco products among the youth, ENDS use is a popu-
lar practice.1,2,8,9

J Oral Pathol Med. 2018;1–7. wileyonlinelibrary.com/journal/jop © 2018 John Wiley & Sons A/S. | 1
Published by John Wiley & Sons Ltd
2 |
According to the National Health Interview Survey, 12.6% of
10
American adults reported that they had ever tried e‐cigarettes.
Younger (18‐24 years old) men, and American Indians or Alaska
Natives were more likely to have tried e‐cigarettes compared to
females, older adults and other races.10 The National Youth Tobacco
Survey (NYTS) is the longest running national data set reporting e‐
cigarette use. Analysis of the NYTS data revealed that in 2017, 3.3%
of middle and 11.7% of high school students had used e‐cigarettes
in the past 30 days.11,12 The popularity of ENDS in general is attrib-
uted to the ease of access, the perception that ENDS are harmless,
or healthier than conventional combustible cigarettes, and heavy
advertisement targeting children and young adults with child‐friendly
flavours such as bubble‐gum, fruit and pina colada.13,14 Although
these numbers are alarmingly high, a slow and steady linear decrease
has occurred in the use of e‐cigarettes by the youth after 2015.11
E‐cigarettes are a $US 10 billion industry and are predicted to
surpass the combustible tobacco market in the next decade.15 There
is a paucity of evidence surrounding the potential detrimental effects
of e‐cigarettes for oral health, and given the great variability of
ENDS, here we review and discuss the systemic and oral health
complications of ENDS.
2 | SYSTEMIC HEALTH RISKS OF
ELECTRONIC NICOTINE DELIVERY SYSTEMS
The majority of safety and toxicity‐based research studies on ENDS
principally feature e‐cigarettes, and thus, due to the scarcity of
research studies on other ENDS, the proceeding section will mainly
focus on the systemic health risks of e‐cigarettes.
Clinical studies on the systemic health risks of e‐cigarettes are
scant and are limited to specific liquid constituents that constantly
continue to change even as the research studies investigating these
16,17
liquid constituents are being conducted. It has recently been
uncovered from a pilot New England Journal of Medicine (NEJM)
study that aerosols released from e‐cigarettes during the “vaping”
process contain hidden formaldehyde.18 Considering that formalde-
hyde is a potent carcinogen, it is likely that chronic e‐cigarette users
(especially high‐voltage e‐cigarette users) may be at an increased risk
of upper aerodigestive tract cancer. Conservative estimates indicate
that vaping at a rate of 3 mL a day would incur an inhalation dose
of approximately 14 mg, whereas the dose inhaled from a pack of
20 conventional combustible cigarettes is approximately 3 mg.18 It
has been suggested that the hidden formaldehyde expressed from e‐
cigarettes may be deposited more efficiently in the respiratory tract
than that of gaseous formaldehyde released from conventional cigar-
ettes.18 Moreover, risk‐based calculations have estimated that the
lifetime cancer risk as a result of long‐term vaping from e‐cigarette
use in terms of formaldehyde exposure can be as high as 15 times
18
more than that of long‐term conventional cigarette use. Several
authors have however contested the findings of this exploratory
NEJM study suggesting that the excessive formaldehyde exposure is
as a result of coil overheating within the e‐cigarette to unrealistic
SULTAN ET AL.
levels.19,20 Coil resistance, an important factor that can dictate the
temperature and power generated from an e‐cigarette, was not
included in the experimental testing.21 These shortcomings have put
into question the scientific rigour of this pilot study, and the overall
formaldehyde exposure reported may be overexaggerated.
Although the cumulative dose of formaldehyde from e‐cigarette
consumption may be significantly greater than of conventional cigar-
ettes, it is noteworthy that conventional cigarettes harbour at least
72 “possible” carcinogens,22 of which the International Agency for
Research on Cancer rates 16 of these compounds as carcinogenic to
humans.23 Furthermore, it has been demonstrated that e‐cigarettes
have a more favourable toxicity profile than conventional cigar-
ettes.24 This is evidenced by a recent study which showed that six
different carcinogenic metabolites were significantly higher in con-
ventional cigarette smokers than in e‐cigarette users.25 Moreover,
previous animal studies have confirmed the tumour‐forming potential
of some of these metabolites.25 Carcinogenic nitrosamines such as
N’‐nitrosonornicotine (NNN) were detected in trace amounts in e‐
cigarettes24,26 but could be detected approximately 380‐fold higher
in conventional cigarettes.24 Both acetaldehyde and acrolein are
putative respiratory irritants, and these carcinogens were detected at
levels 450‐fold and 15‐fold higher in conventional cigarettes,
respectively.24
The pulmonary effects of conventional cigarettes are well known;
however, little is known about the pulmonary effects of e‐cigarettes.
In a novel murine model investigating the effect of e‐cigarette expo-
sure on pulmonary anti‐microbial defences, a modified e‐cigarette
inhalation chamber was utilized and it was found that mice exposed
to e‐cigarettes demonstrated defective bacterial clearance due to
diminished alveolar macrophage phagocytosis.27 E‐cigarettes and
associated copper nanoparticles have also been shown to induce
mitochondrial oxidative stress and promote DNA fragmentation in
human lung fibroblasts.28 Additionally, e‐cigarette flavouring agents
such as diacetyl have been detected above the standard laboratory
limits in commercially available e‐cigarettes and this is of concern as
diacetyl has been attributed to cases of bronchiolitis obliterans.29
Conflicting studies on the cardiovascular side‐effects of e‐cigarettes
exist as some studies report an increase in heart rate and elevation
in diastolic blood pressure following short‐term e‐cigarette vaping,
with other studies reporting no increase in heart rate or elevation in
diastolic blood pressure.17
The recent advent of “vitamin vaping” and aggressive marketing
by some e‐cigarette companies that claim that vaping e‐cigarettes
containing a variety of vitamins (vitamins A, B12, C, and D) is worry-
ing as at this current time, clinically determining the concentration of
any given vitamin that is systemically absorbed by inhalation route is
not possible. Systemic inhalation of heated vitamins via e‐cigarette
vapour has far‐reaching implications that have not yet been investi-
gated. For instance, one e‐cigarette company has claimed that a few
puffs of their B12 vitamin containing e‐cigarette can provide 10
times the recommended daily dose of vitamin B12. It is therefore
possible that a regular user of vitamin e‐cigarettes could develop
vitamin toxicity from overexposure. Furthermore, vitamin B12
SULTAN ET AL.
supplementation has been associated with an increased risk of lung
cancer in males and high circulating levels of vitamin D has been
linked to prostate cancer.30,31
A systematic literature review conducted by the FDA concluded
that a litany of toxic and carcinogenic substances have been identi-
fied in e‐cigarettes but importantly, the levels of these substances
differ considerably between different ENDS and the methodologies
32
used within the studies reviewed were not well validated. In addi-
tion, a joint policy statement by the American Society of Clinical
Oncology (ASCO) and the American Association for Cancer Research
(AACR) stated that, at this current time, there is insufficient data on
33
the long‐term health consequences of ENDS. The joint policy reit-
erated the need for additional research in this area, and the expert
committee explicitly advocated for in vitro, in vivo and clinical stud-
ies to assess the physiologic effects of aerosol exposure from
33
ENDS.
It is still not known however what other harmful carcinogenic
compounds exist in ENDS. Misleading and missing information on
product ingredients of many of the commercially available e‐cigar-
ettes exists.17 It is plausible that hidden harmful compounds exist in
e‐cigarettes that have yet to be discovered. Further research is
needed to determine the full breadth of the possible carcinogenic
compounds found in ENDS and to what extent the vaporized car-
cinogenic effect from these compounds has on the respiratory tract
and on overall cancer risk. Standardization of testing protocols is
currently lacking, and severe conflicts of interests exist within cur-
17
rently published studies. These conflicts of interest arise because
several studies were funded by e‐cigarette manufacturers, and many
authors involved in the studies were consultants for said manufac-
17
turers. Therefore, attempts should be made in future studies to
ensure standardization of testing protocols and to ensure no con-
flicts of interest exist. Furthermore, longitudinal studies are needed
to enhance our knowledge of the long‐term systemic effects of
ENDS.
3 | ORAL HEALTH RISKS AND ORAL
CANCER RISK OF ELECTRONIC NICOTINE
DELIVERY SYSTEMS
Little is known about the oral health risks of ENDS, and to date, few
studies have characterized ENDS‐related oral mucosal sequelae.
Notably, as ENDS are relatively new to the market, no long‐term
studies exist. Xerostomia was the most common side‐effect of e‐
cigarette use reported according to a 2014 worldwide questionnaire‐
34
based survey of 19 414 e‐cigarette users. A statistically significant
increased prevalence of nicotine stomatitis, hairy tongue and angular
cheilitis was reported in a recent prospective case‐control study
comparing oral mucosal lesions in e‐cigarette users (n = 45) and for-
mer conventional cigarette smokers (who had quit smoking at least
6 months prior to the start of the study; n = 45).35 It is plausible
that ENDS users can incur an increased incidence of nicotine stom-
atitis considering that the e‐liquid within ENDS is vaporized by heat
| 3
and this heat can in turn cause nicotine stomatitis. Owing to the
small sample size and the fact that current cigarette smokers were
not assessed in this study, the results of this study must be inter-
preted with caution. Furthermore, nicotine stomatitis usually resolves
within 2 weeks after cessation of smoking, and therefore, comparing
nicotine stomatitis occurrence in e‐cigarette users to former smokers
is not clinically relevant.
It has been suggested that e‐cigarettes may affect oral mucosal
blood flow and enhance perfusion of oral tissues. In a small 2016
pilot study of 10 subjects, a laser Doppler device was used to assess
capillary buccal mucosal blood flow before and immediately follow-
ing e‐cigarette vaping.36 There was a transient measurable increase
in capillary perfusion following vaping but this returned to baseline
after 30 minutes. It is not clear what clinically meaningful conclu-
sions can be drawn from this study as there were no control groups
and a very limited sample size was studied.
Intra‐oral explosion injuries from e‐cigarettes have been
reported and represent an uncommon complication of e‐cigarette
use. Explosion blast injuries from overheating of the internal
lithium‐ion battery during the vaping process have resulted in sev-
eral oral injuries that include but are not limited to tooth fracture,
tooth avulsion, dento‐alveolar fracture, haematoma formation, trau-
matic ulceration and tattooing, intra‐oral burns and subsequent
necrosis, palatal perforation with extension into the nasal cavity,
and extensive soft tissue deficits requiring considerable cosmetic
and functional corrective surgery.37-40
Few studies have characterized the effects of ENDS on the peri-
odontium but those that have, show that e‐cigarettes contribute to
the pathogenesis of periodontitis.41,42 Human periodontal ligament
fibroblasts when incubated in menthol‐flavoured e‐cigarette liquid
showed statistically significant diminished proliferation rates when
compared to controls.43 A similar study involving human gingival
fibroblasts showed significant cytotoxicity and apoptosis induction
following 48 hours of e‐cigarette exposure.44 Many of these primary
studies however lack important pertinent control groups.
A diverse oral microbiome halts oral dysbiosis and maintains an
ecological balance within the oral cavity.45 This balance is important
as oral dysbiosis can contribute to many oral diseases, and if severe,
may even contribute to systemic dysbiosis. Disruption of the oral
microbiome from cigarette smoke may result in the overgrowth of a
commensally occurring species and in turn lead to a shift to a
pathogenic state of that species. A 2018 case‐control pilot study
which characterized the oral microbiome via 16S RNA sequencing
of e‐cigarette users (n = 10), current smokers (n = 10) and matched
controls (n = 10) revealed that the bacterial profile of current smok-
ers differed significantly compared to controls and e‐cigarette
users.46 Moreover, the oral microbiome of e‐cigarette users was
comparable to the control group. The authors conclude that e‐cigar-
ette vapour exposure on the oral cavity does not alter the microbial
flora; however, this study had several limitations that include the
relatively small sample size, the cross‐sectional study design (no lon-
gitudinal sampling was performed) and the sex‐cohort mismatch
(only 2/30 participants were female), and one e‐cigarette user was
4 |
not excluded even though this subject reported occasional concomi-
tant conventional cigarette use. Furthermore, only the buccal
mucosa and saliva were sampled. Ongoing studies continue to char-
acterize the oral microbiome of ENDS users, and it is important that
these studies include larger samples sizes, sample many oral sites
that include periodontal sites and provide longitudinal sampling of
different sites of the oral cavity. In addition, it is suggested that sim-
ilar oral mycobiome studies be carried out in ENDS users. This is
prudent as certain strains of Candida have been associated with the
induction and promotion of oral dysplasia.47-49 Characterizing the
oral mycobiome in ENDS users may shed new light on whether
these patients harbour specific high‐risk potentially carcinogenic
Candida strains.
The data on the risk of developing oral dysplastic lesions or
frank squamous cell carcinoma secondary to ENDS are virtually
non‐existent. A case‐control study utilizing the micronucleus assay
test from buccal mucosa exfoliative cytology scrapings in current
smokers (n = 23), e‐cigarette users (n = 22) and non‐smokers (n = 20)
determined that e‐cigarette use was safe for oral mucosal cells on the
basis of a statistically significant decrease in prevalence of micronu-
50
clei in e‐cigarette users compared to current smokers. However,
this study had many limitations. In addition to a small sample size and
the non‐blinded nature of the study, the micronucleus assay test is
not a well‐validated test for use in the oral cavity. Further, the e‐
cigarette group had study subjects who also concomitantly used con-
ventional cigarettes. It is known that NNN found in conventional
cigarettes and in smokeless tobacco products is a potent carcinogen
and has been proven to induce oral squamous cell carcinoma in
rats.51 Extrapolating from this, it is likely that the induction of oral
squamous cell carcinoma (OSCC) secondary to e‐cigarettes would be
much less considering that e‐cigarettes contain trace amounts of
NNN.24,26
Cotinine, a measurable metabolite of nicotine and an established
biomarker of nicotine uptake, has been found at high levels in saliva
of e‐cigarette users52,53 and at levels similar to that of conventional
cigarette smokers.54 It is well known that nicotine is the principal
agent responsible for the addictiveness of conventional cigarette
smoking. However, the carcinogenic potential of nicotine is not as
well studied. In vitro evidence nevertheless does suggest that nico-
tine may possess tumour promoting effects.55 In fact, animal studies
have indicated that nicotine can suppress apoptosis56 and induce
57
migration of OSCC cells. A recent 2018 study showed that nico-
tine was capable of inducing migration of oral dysplastic cells via
fatty acid synthase‐dependent epidermal growth factor receptor acti-
vation.58 More pointedly, the authors raised potential concerns
about e‐cigarette safety especially in former smokers where nicotine
could trigger oncogenic signals that could lead to dysplastic changes
in pre‐existing oral potentially malignant conditions and in turn lead
to transformation to OSCC.58 Yu et al59 in 2016 showed that e‐
cigarette vapour, irrespective of whether the e‐liquid contained nico-
tine or not, was cytotoxic and was a DNA strand breaking‐inducing
agent to normal epithelial cell lines and head and neck squamous cell
carcinoma cell lines. This in vitro study was highly criticized for
SULTAN ET AL.
several methodological design flaws and the lack of relevant compar-
isons with conventional cigarette smoke.60
It is important to note that ENDS currently available on the mar-
ket differ significantly in terms of their voltage and liquid contents,
and therefore, it is likely that the oral health effects and oral cancer
risk vary between products. An additional complicating factor is that
ENDS are not currently regulated in many countries which may fur-
ther lead to differences in their contents and operating power.16
Consequently, future studies investigating the oral health effects of
ENDS should consider testing several of the commercially available
ENDS. As a large proportion of current and former conventional
cigarette smokers use ENDS, it may be difficult to determine
whether oral lesions are directly a result of ENDS use or the conse-
quence of previous or current concomitant conventional cigarette
use. Thus, if feasible, future randomized controlled trials should
endeavour to include ENDS‐only study groups, that is, subjects who
have never smoked conventional cigarettes before. It is unknown
whether the use of ENDS can accentuate the effects of tobacco
smoke in current conventional smokers trying to quit smoking. It is
also not known whether the use of ENDS in virgin smokers may act
as a gateway to tobacco smoking and in turn increase the likelihood
of already established tobacco‐related oral mucosal sequelae.
As has been the case for conventional cigarettes, it is likely that
ENDS will be consumed for many years before their true carcino-
genic potential is realized, and therefore, prospective longitudinal
studies on the role of ENDS on oral cancer risk are highly desirable.
4 | ELECTRONIC NICOTINE DELIVERY
SYSTEMS: SMOKING CESSATION
The benefits of smoking cessation are well documented. However,
despite the efforts made by many smokers, only half of the individu-
als who attempt to quit smoking remain abstinent for a week; this
number drops even lower, to <5% at the 1‐year mark post‐cessa-
tion.61 Dependence on tobacco has primarily been attributed to
nicotine and its effects on the brain's reward system, and secondly
on sensory and behavioural cues.62,63 While nicotine patches,
lozenges, sprays, inhalers, bupropion SR and varenicline have been
approved as safe strategies to increase the chances of cessation, the
efficacy of these techniques remains guarded as successful long‐term
smoking cessation requires additional psycho‐social support.64
Another shortcoming of the above‐mentioned strategies is that they
fail to address the sensory/behavioural aspects of smoking. Through
satisfying the sensory and behavioural cues (eg, being handheld
devices, the ability to take a puff and causing a “scratch” sensation
in the throat) in addition to nicotine delivery, ENDS have become a
popular gateway to, or even alternative for, smoking cessation.65
As discussed above, ENDS are extremely variable in their compo-
sition and active ingredients, and thus, this challenges the validity of
any general assessment made. Therefore, ENDS should be examined
not as a global class of smoking cessation/alternative device, but
rather as individual types, each with specific characteristics.
SULTAN ET AL.
Regardless of the brand or generation, toxin levels of the tested
ENDS have been shown to be lower than those of cigarettes and
the use of ENDS has been associated with fewer adverse events.66
Although the initial devices have low nicotine delivery to naïve
users, they have been shown to successfully relieve the users’ urge
to smoke.67,68 In contrast, the second‐generation ENDS provide
more choices (both nicotine concentration and flavours) and have
better nicotine delivery capacity and, not surprisingly, are more suc-
cessful as smoking cessation devices compared to cigalike counter-
parts.69,70 A meta‐analysis of published randomized controlled trials
(RCT) evaluating the efficiency of ENDS as smoking cessation aids
confirmed that smokers who used ENDS were significantly more
likely to stop smoking than those who did not use ENDS.66
The efficacy and safety of ENDS for smoking cessation are heat-
edly debated. Currently, the two major obstacles in recommending
ENDS as a definite or safer alternative to smoking include the fol-
lowing: (a) high variability in the composition of ENDS and limited
data regarding their safety; and (b) small number of clinical trials
focusing on the use of ENDS for smoking cessation. At this time,
there is no definitive evidence from clinical trials suggesting any
adverse health outcomes associated with the short‐term use of
ENDS, and as such, further randomized clinical trials in larger popula-
tion cohorts are required to reach consensus.
5 | ELECTRONIC NICOTINE DELIVERY
SYSTEMS: THE DENTAL TEAM'S ROLE IN
SMOKING CESSATION
High annual attendance levels suggest that dental healthcare provi-
ders are well placed to counsel their patients on smoking cessation.
The increasing use of ENDS by the general public means that den-
tal healthcare providers are more likely now to encounter questions
on their effects on the periodontium and on the oral cavity proper.
The safety and effectiveness of their use as a smoking cessation
aid is an important discussion that members of the dental team
should have with their patients especially considering that intensive
counselling by dental healthcare providers using current methods
has only yielded 1‐year smoking cessation rates of 7%.71 If a
patient volunteers their willingness to cease tobacco smoking, the
dentist should offer specific assistance and follow-up care72, and
moreover, the dentist should inform their patients that systemic
and oral long term effects of ENDS have yet to be elucidated. The
dentist should also familiarize themselves with any available health
advisory consensus statements on the use of ENDS for smoking
cessation in their jurisdiction. Smoking cessation training courses
for the entire dental team with specific emphasis on ENDS are
highly encouraged.
In light of the equivocal evidence and lack of long‐term studies
evaluating the benefits and safety risks of ENDS, members of the
dental team should continue to advocate current FDA‐approved
smoking cessation tools until new robust evidence showing the ben-
efits of ENDS comes to light. This is supported by the European
| 5
Public Health Association (EUPHA) which advocates “all concerned
to reduce smoking to maintain their focus on evidence‐based mea-
sures”.73 This is also supported by a recent American Academy of
Oral Medicine (AAOM) clinician's guide to tobacco cessation which
stated that at this current juncture, advocating the use of ENDS as a
“smoking cessation tool in the presence of various other available
carcinogen‐free FDA‐approved smoking cessation aids is medicole-
gally ill‐advised”.74 As we await the results of many ongoing studies,
and of an important recently completed randomised controlled trial
on smoking cessation and the oral health effects of e‐cigarettes
(NIHR Portfolio Study. UKCRN ID: 16964), we should apply a cau-
tious and evidenced‐based approach to ENDS.
6 | CONCLUSIONS AND FUTURE
DIRECTIONS FOR RESEARCH
Xerostomia is the most common oral complaint secondary to ENDS
use and the oral findings in ENDS users include but are not limited
to nicotine stomatitis, hairy tongue and angular cheilitis.34,35 In vitro
studies have found ENDS vapour to induce double‐strand breaks in
DNA of normal and head and neck squamous cell carcinoma cell
lines.59 DNA double‐strand breaks are the most lethal form of DNA
damage; if left unrepaired, they can result in chromosomal rearrange-
ment and carcinogenesis.
Currently, there is no strong evidence suggesting a direct role for
ENDS in pathogenesis of oral potentially malignant disorders or oral can-
cer. Given their relative success in smoking cessation, ENDS have been
proposed as a safe and effective strategy for smoking cessation and
some even advocate these devices as cancer‐prevention modalities.50
Notably, despite the unknown pathogenesis of oral cancer, given
that most patients are diagnosed in their 7th decade, oral cancer is
thought to be a product of cumulative mutations.75 More impor-
tantly, given that ENDS are relatively new, their adverse oral seque-
lae may yet to be discovered. As such, one must caution against
considering and promoting ENDS as safe devices for smoking cessa-
tion until further evidence regarding their long‐term use and health
complications is available.
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How to cite this article: Sultan AS, Jessri M, Farah CS.
Electronic nicotine delivery systems: Oral health implications
and oral cancer risk. J Oral Pathol Med. 2018;00:1–7.
https://doi.org/10.1111/jop.12810