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Acta Odontologica Scandinavica
ISSN: 0001-6357 (Print) 1502-3850 (Online) Journal homepage: http://www.tandfonline.com/loi/iode20
Oral mucosal lesions in electronic cigarettes
consumers versus former smokers
Elena Bardellini, Francesca Amadori, Giulio Conti & Alessandra Majorana
To cite this article: Elena Bardellini, Francesca Amadori, Giulio Conti & Alessandra Majorana
(2018) Oral mucosal lesions in electronic cigarettes consumers versus former smokers, Acta
Odontologica Scandinavica, 76:3, 226-228, DOI: 10.1080/00016357.2017.1406613
To link to this article: https://doi.org/10.1080/00016357.2017.1406613
Published online: 21 Nov 2017.
Submit your article to this journal
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ORIGINAL ARTICLE
Oral mucosal lesions in electronic cigarettes consumers versus former smokers
Elena Bardellinia
, Francesca Amadoria
, Giulio Contib
and Alessandra Majoranaa
a
Department of Medical and Surgical Specialities, Radiological Sciences and Public Health, Dental School, University of Brescia, Brescia, Italy;
b
Department of Oral Surgery, University Vita-Salute San Raffaele, Milan, Italy
ABSTRACT
Objectives: Electronic cigarettes (ECs) have become very popular in recent years. However, many
uncertainties remain about their side effects. This study aims to evaluate the prevalence and character-
istics of oral mucosal lesions (OMLs) in former smokers compared to ECs consumers.
Methods: A prospective case-control study was carried out. Outpatients for dental consultation were
consecutively enrolled into two groups based on their habits, i.e. former smokers and ECs consumers.
Each patient was examined to detect possible oral lesions and, if needed, a swab or biopsy of the
lesion was taken for diagnosis. Data was entered into a spreadsheet and analyzed.
Results: A total of 90 patients were examined, 45 were former smokers (group A) and 45 were ECs
consumers (group B). OMLs were detected in 55 cases, of which 19/55 (34.6%) belonged to group A
and 36/55 (65.4%) to group B. Nicotine stomatitis, a hairy tongue and angular cheilitis resulted to be
significantly more common among EC consumers.
Conclusions: We found no statistically significant differences in terms of total prevalence of OMLs
between former smokers and ECs consumers. An increased prevalence of three specific types of OMLs
was detected among ECs consumers.
ARTICLE HISTORY
Received 1 June 2017
Revised 17 October 2017
Accepted 6 November 2017
KEYWORDS
Smoking; oral lesion;
electronic cigarette
Introduction
Electronic cigarettes (ECs) are battery-powered, nicotine-deliv-
ery devices marketed as safe substitutes for traditional ciga-
rettes [1]. In recent years, ECs have rapidly gained popularity.
Although ECs were developed as a safer alternative to smok-
ing tobacco products, there is a growing body of evidence to
substantiate that their produced aerosols contain low levels
of toxicants and carcinogens, though generally lower than
the quantities found in conventional tobacco cigarettes [2,3].
The few existing toxicological studies investigating the cel-
lular effects of exposure to ECs’ aerosol in human bronchial
cells have produced conflicting results. Some studies seem to
indicate either no or very little toxicity from ECs in vitro [4],
while others suggest potential oxidative stress and inflamma-
tory response [5,6].
Relatively little is known about the clinical effects of the
ECs on the oral mucosa, especially on a long-term basis. This
study aims to investigate the oral mucosal lesions (OMLs) in
ECs consumers.
Materials and methods
Study population
This case-control study was performed at the Dental Clinic
of the University of Brescia, within a 2-year period, from
January 2015 to December 2016 on consecutively enrolled
patients.
The study was undertaken on former cigarettes smokers
and current EC users. Former smokers were defined as daily
or almost daily smokers, who had smoked at least 100 ciga-
rettes in their lifetime and who had quit smoking from at
least 6 months to a maximum of 2 years prior to their
involvement in the study. EC consumers considered were
those who had been smoking ECs for at least 6 months.
Inclusion criteria were: age older than 18 years, no dental
procedures in the last six months, no chronic alcoholism,
no occupational exposure to carcinogens, no history of
malignancy.
OMLs were classified following the WHO criteria [7].
Patients were examined by two calibrated clinicians (EB, FA)
under standardized conditions, with artificial lighting and
with a mouth mirror. If needed, the clinical diagnosis was
confirmed by a swab or biopsy of the lesion. Carious lesions,
endodontic lesions and periodontal lesions were excluded
from the oral lesions studied.
The following data was recorded from each patient: age,
gender, systemic chronic diseases, clinical aspects of the
OMLs and eventual histological diagnosis.
Data analysis
The data was put on a spreadsheet. A 5% level of signifi-
cance was used and the data was analyzed using RV
R
software
for Mac. Descriptive analysis, bivariate analysis and Fisher’s
test were used.
CONTACT Elena Bardellini elena.bardellini@unibs.it Dental Clinic, P.le Spedali Civili 1, 25123 Brescia, Italy
ß 2017 Acta Odontologica Scandinavica Society
ACTA ODONTOLOGICA SCANDINAVICA, 2018
VOL. 76, NO. 3, 226–228
https://doi.org/10.1080/00016357.2017.1406613
Ethical considerations
The research was conducted in accordance with the princi-
ples of the Declaration of Helsinki. All subjects gave a written
informed consent indicating their voluntary and anonymous
participation in the study. They completed a questionnaire
that collected demographic data and information on the con-
sumption of cigarettes/e-cigarettes, use of alcohol, exposure
to occupational carcinogens and the presence of concomi-
tant or previous systemic diseases.
Results
During the 2-year period, we consecutively enrolled former
smokers and EC consumers in order to have two numerically
similar groups. Ninety patients met the inclusion criteria, 45
were former smokers (group A) and 45 were EC consumers
(group B). Group A was composed of 23 females and 22
males (mean age 47 ± 11) while group B contained four
females and 41 males (mean age 47 ± 10). About 43.3% of
the patients (n ¼ 39) had some form of the systemic disease,
which included diabetes (n ¼ 8), hypertension (n ¼ 16), heart
disease (n ¼ 8) or HCV (n ¼ 5). The sociodemographic data is
shown in Table 1.
OMLs were detected in 55 cases, of which 34.6% (n¼ 19/55)
belonged to group A and 65.4% (n ¼ 36/55) to group B. Nine
different types of OMLs were detected. The type and distribu-
tion of the lesions are shown in Table 2.
Discussion
E-cigarettes are currently used to stop smoking or at least
reduce the consumption of traditional cigarettes. However,
the Food and Drug Administration has yet to fully regulate
the composition or given approval of the e-liquid contained
by ECs, although it has provided information about the
known side effects of such usage (e.g. congestive heart fail-
ure, cough, hypotension, and mental confusion) and defined
the common components found in these liquids [8].
There have been few studies that address the direct
health effect of EC smoking, especially regarding the oral
mucosa. A recent study [9] based on cytological examination
of scrapings from the oral mucosa in three groups of patients
(smokers, ECs smokers, and non-smokers) demonstrated that
there were no statistically significant differences in the micro-
nuclei distribution, suggesting that the use of ECs seems to
be safe for oral cells. On the other hand, Reuther et al. [10]
found that ECs may have an effect on the blood flow (meas-
ured using a laser Doppler) of the oral mucosa. The laser
Doppler measurements were expressed as arbitrary perfusion
units: a significant difference in the arbitrary perfusion units
was found with respect to the baseline capillary blood flow
after vaping with both nicotine and nicotine-free ECs.
However, the Doppler measurements were not performed in
smokers.
The pathologic effects on the oral mucosa in terms of clin-
ical OMLs have yet to be thoroughly evaluated and therefore,
to our knowledge; this is the first report describing OMLs in
ECs consumers. Before discussing the results of this study, it
should be emphasized that the study was carried out on a
small sample of patients, so the findings must be considered
preliminary.
From our results, the prevalence of total OMLs was higher
among ECs consumers, but the difference between the two
groups was not statistically significant. One of the most com-
mon lesions in both groups was smoker’s melanosis and this
was consistent with the observations made by Saraswathi
et al. [11] and Hedin et al. [12]. Polycyclic amines such as
nicotine and benzopyrenes, present in tobacco, can activate
the production of melanin by melanocytes, perhaps as a pro-
tective mechanism of the oral mucosa against tobacco
agents. Tobacco-associated melanin pigmentation has been
reported in about 22% of smokers and is dose-dependent. In
our study, the prevalence of such pigmentation was we
found no difference between the former tobacco smokers
and the EC consumers, confirming that former smokers have
a lower incidence of melanosis [13], as the cessation of
tobacco usage can be sufficient in reducing or eliminating
the pigmentation.
Table 1. Demographic characteristics of the group A (former smokers) and of
the group B (EC consumers).
Group A (n ¼ 45) Group B (n ¼ 45)
Gender
Male 22 41
Female 23 4
Mean age 47 þ 11 47 þ 10
Systemic diseases 16 23
Diabetes 3 5
Hypertension 9 7
Heart disease 2 6
HCV 2 5
Table 2. Distribution of OMLs in the group A (former smokers) and in the group B (EC consumers).
Oral mucosal lesions Group A (45) n (%) Group B (45) n (%) OR (95% CI) p Value
Melanosis 5 (11.1) 6 (13.3) 1.23 .74
Nicotine stomatitis 1 (2.2) 6 (13.3) 6.77 .04
Hairy tongue 1 (2.2) 7 (15.5) 8.11 .02
Hyperplastic candidiasis 2 (4.4) 8 (17.7) 4.65 .04
Median rhomboid glossitis 3 (6.6) 4 (8.8) 1.37 .69
Lichen planus 2 (4.4) 0 0 .15
Erythematous candidiasis 2 (4.4) 4 (8.8) 2.1 .39
Leukoplakia 2 (4.4) 1 (2.2) 2.05 .55
Hyperkeratosis 2 1
Dysplasia 0 0
Squamous cell carcinoma 1 (2.2) 0 (0) 0 .31
Total 19 36 0.42 .28
Significant, p value  .05.
ACTA ODONTOLOGICA SCANDINAVICA 227
Regarding other OMLs, nicotine stomatitis occurred more
frequently in 6/45 EC consumers and only in 1/45 former
smokers (p ¼ .04). The many irritants, toxins and carcinogens,
found naturally in tobacco, cause the typical opacification or
keratinization of the palate seen as red dots surrounded by
white keratotic rings [14]. Although ECs do not contain as
many ingredients as conventional tobacco, they are vapor-
ized by heat starting from a liquid solution (a mixture of pro-
pylene glycol, glycerine, nicotine and flavouring) [15]. The
nicotine content in ECs varies widely among brands, typically
ranging from 0 to 34 mg/ml [16]. Emissions from ECs may
also contain fine particles of flavours, aroma transporters, gly-
cerol, propylene glycol, nicotine, trace amounts of carcino-
gens, heavy metals and other chemicals [1].
We can speculate that nicotine stomatitis in ECs consum-
ers may depend not only on the exposure of the palatal
mucosa to nicotine but also to some of these chemical com-
pounds. For instance, a recent study found that the product
characteristics of electronic nicotine delivery systems, includ-
ing flavouring, might induce inhalation toxicity, with a straw-
berry-flavoured product being the most cytotoxic [17].
Likewise, we can also interpret the high percentage of
hyperplastic candidiasis in the retrocommissural area (17.8%)
found in the group of ECs consumers (p ¼ .04). Many cross-
sectional studies show a higher prevalence of hyperplastic
candidasis among smokers while there are no data about ECs
consumers. Candidal ability to invade superficial layers of the
epithelium, aided by their hyphal appendages with tips con-
taining concentrated amounts of candidal proteinases
(secreted aspartyl proteinases [SAP]) and lipases – is optimal
at acidic pH. Several studies have shown that many protect-
ive salivary proteins such as lactoferrin, lactoperoxidase, and
immunoglobulins, especially IgA1 and IgA2, are susceptible
to degradation by candidal SAPs. We can presume that
hyperplastic candidiasis in ECs consumers could be favoured
by a pH alteration induced by the aforementioned chemical
compounds [18].
Hairy tongue resulted in a statistically greater prevalence
among EC consumers than in former smokers. There are
numerous initiating or predisposing factors for the abnormal
coating on the dorsal surface of the tongue, particularly with
smoking-associated pH changes [14]. We can speculate that
the mucosal changes may also arise from other factors, i.e.
the mucosal drying effects, the high intraoral temperatures,
intraoral pH changes, local alteration of membrane barriers
and immune responses, or altered resistance to fungal and
viral infections.
No differences in terms of precancerous OMLs (lichen pla-
nus, leukoplakia) were found between the two groups. Only
one case of squamous cell carcinoma was found on the lat-
eral surface of the tongue in a 52-year-old former smoker.
Our results show that e-cigarettes are linked to three
types of inflammatory lesions in the oral cavity. Future case-
control or cohort studies for individual lesions with larger
sample sizes are necessary to evaluate the risk for OMLs
resulting from EC habits.
Disclosure statement
No potential conflict of interest was reported by the authors.
References
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Circulation. 2014;129:1972–1986.
[2] Kim KH, Kabir E, Jahan SA. Review of electronic cigarettes as
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2016;34:262–275.
[3] Goniewicz ML, Knysak J, Gawron M, et al. Levels of selected carci-
nogens and toxicants in vapour from electronic cigarettes. Tob
Control. 2014;23:133–139.
[4] Misra M, Leverette RD, Cooper BT, et al. Comparative in vitro tox-
icity profile of electronic and tobacco cigarettes, smokeless
tobacco and nicotine replacement therapy products: e-liquids,
extracts and collected aerosols. Int J Environ Res Public Health.
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bardellini2017 (1).pdf

  • 1. Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=iode20 Acta Odontologica Scandinavica ISSN: 0001-6357 (Print) 1502-3850 (Online) Journal homepage: http://www.tandfonline.com/loi/iode20 Oral mucosal lesions in electronic cigarettes consumers versus former smokers Elena Bardellini, Francesca Amadori, Giulio Conti & Alessandra Majorana To cite this article: Elena Bardellini, Francesca Amadori, Giulio Conti & Alessandra Majorana (2018) Oral mucosal lesions in electronic cigarettes consumers versus former smokers, Acta Odontologica Scandinavica, 76:3, 226-228, DOI: 10.1080/00016357.2017.1406613 To link to this article: https://doi.org/10.1080/00016357.2017.1406613 Published online: 21 Nov 2017. Submit your article to this journal Article views: 95 View related articles View Crossmark data
  • 2. ORIGINAL ARTICLE Oral mucosal lesions in electronic cigarettes consumers versus former smokers Elena Bardellinia , Francesca Amadoria , Giulio Contib and Alessandra Majoranaa a Department of Medical and Surgical Specialities, Radiological Sciences and Public Health, Dental School, University of Brescia, Brescia, Italy; b Department of Oral Surgery, University Vita-Salute San Raffaele, Milan, Italy ABSTRACT Objectives: Electronic cigarettes (ECs) have become very popular in recent years. However, many uncertainties remain about their side effects. This study aims to evaluate the prevalence and character- istics of oral mucosal lesions (OMLs) in former smokers compared to ECs consumers. Methods: A prospective case-control study was carried out. Outpatients for dental consultation were consecutively enrolled into two groups based on their habits, i.e. former smokers and ECs consumers. Each patient was examined to detect possible oral lesions and, if needed, a swab or biopsy of the lesion was taken for diagnosis. Data was entered into a spreadsheet and analyzed. Results: A total of 90 patients were examined, 45 were former smokers (group A) and 45 were ECs consumers (group B). OMLs were detected in 55 cases, of which 19/55 (34.6%) belonged to group A and 36/55 (65.4%) to group B. Nicotine stomatitis, a hairy tongue and angular cheilitis resulted to be significantly more common among EC consumers. Conclusions: We found no statistically significant differences in terms of total prevalence of OMLs between former smokers and ECs consumers. An increased prevalence of three specific types of OMLs was detected among ECs consumers. ARTICLE HISTORY Received 1 June 2017 Revised 17 October 2017 Accepted 6 November 2017 KEYWORDS Smoking; oral lesion; electronic cigarette Introduction Electronic cigarettes (ECs) are battery-powered, nicotine-deliv- ery devices marketed as safe substitutes for traditional ciga- rettes [1]. In recent years, ECs have rapidly gained popularity. Although ECs were developed as a safer alternative to smok- ing tobacco products, there is a growing body of evidence to substantiate that their produced aerosols contain low levels of toxicants and carcinogens, though generally lower than the quantities found in conventional tobacco cigarettes [2,3]. The few existing toxicological studies investigating the cel- lular effects of exposure to ECs’ aerosol in human bronchial cells have produced conflicting results. Some studies seem to indicate either no or very little toxicity from ECs in vitro [4], while others suggest potential oxidative stress and inflamma- tory response [5,6]. Relatively little is known about the clinical effects of the ECs on the oral mucosa, especially on a long-term basis. This study aims to investigate the oral mucosal lesions (OMLs) in ECs consumers. Materials and methods Study population This case-control study was performed at the Dental Clinic of the University of Brescia, within a 2-year period, from January 2015 to December 2016 on consecutively enrolled patients. The study was undertaken on former cigarettes smokers and current EC users. Former smokers were defined as daily or almost daily smokers, who had smoked at least 100 ciga- rettes in their lifetime and who had quit smoking from at least 6 months to a maximum of 2 years prior to their involvement in the study. EC consumers considered were those who had been smoking ECs for at least 6 months. Inclusion criteria were: age older than 18 years, no dental procedures in the last six months, no chronic alcoholism, no occupational exposure to carcinogens, no history of malignancy. OMLs were classified following the WHO criteria [7]. Patients were examined by two calibrated clinicians (EB, FA) under standardized conditions, with artificial lighting and with a mouth mirror. If needed, the clinical diagnosis was confirmed by a swab or biopsy of the lesion. Carious lesions, endodontic lesions and periodontal lesions were excluded from the oral lesions studied. The following data was recorded from each patient: age, gender, systemic chronic diseases, clinical aspects of the OMLs and eventual histological diagnosis. Data analysis The data was put on a spreadsheet. A 5% level of signifi- cance was used and the data was analyzed using RV R software for Mac. Descriptive analysis, bivariate analysis and Fisher’s test were used. CONTACT Elena Bardellini elena.bardellini@unibs.it Dental Clinic, P.le Spedali Civili 1, 25123 Brescia, Italy ß 2017 Acta Odontologica Scandinavica Society ACTA ODONTOLOGICA SCANDINAVICA, 2018 VOL. 76, NO. 3, 226–228 https://doi.org/10.1080/00016357.2017.1406613
  • 3. Ethical considerations The research was conducted in accordance with the princi- ples of the Declaration of Helsinki. All subjects gave a written informed consent indicating their voluntary and anonymous participation in the study. They completed a questionnaire that collected demographic data and information on the con- sumption of cigarettes/e-cigarettes, use of alcohol, exposure to occupational carcinogens and the presence of concomi- tant or previous systemic diseases. Results During the 2-year period, we consecutively enrolled former smokers and EC consumers in order to have two numerically similar groups. Ninety patients met the inclusion criteria, 45 were former smokers (group A) and 45 were EC consumers (group B). Group A was composed of 23 females and 22 males (mean age 47 ± 11) while group B contained four females and 41 males (mean age 47 ± 10). About 43.3% of the patients (n ¼ 39) had some form of the systemic disease, which included diabetes (n ¼ 8), hypertension (n ¼ 16), heart disease (n ¼ 8) or HCV (n ¼ 5). The sociodemographic data is shown in Table 1. OMLs were detected in 55 cases, of which 34.6% (n¼ 19/55) belonged to group A and 65.4% (n ¼ 36/55) to group B. Nine different types of OMLs were detected. The type and distribu- tion of the lesions are shown in Table 2. Discussion E-cigarettes are currently used to stop smoking or at least reduce the consumption of traditional cigarettes. However, the Food and Drug Administration has yet to fully regulate the composition or given approval of the e-liquid contained by ECs, although it has provided information about the known side effects of such usage (e.g. congestive heart fail- ure, cough, hypotension, and mental confusion) and defined the common components found in these liquids [8]. There have been few studies that address the direct health effect of EC smoking, especially regarding the oral mucosa. A recent study [9] based on cytological examination of scrapings from the oral mucosa in three groups of patients (smokers, ECs smokers, and non-smokers) demonstrated that there were no statistically significant differences in the micro- nuclei distribution, suggesting that the use of ECs seems to be safe for oral cells. On the other hand, Reuther et al. [10] found that ECs may have an effect on the blood flow (meas- ured using a laser Doppler) of the oral mucosa. The laser Doppler measurements were expressed as arbitrary perfusion units: a significant difference in the arbitrary perfusion units was found with respect to the baseline capillary blood flow after vaping with both nicotine and nicotine-free ECs. However, the Doppler measurements were not performed in smokers. The pathologic effects on the oral mucosa in terms of clin- ical OMLs have yet to be thoroughly evaluated and therefore, to our knowledge; this is the first report describing OMLs in ECs consumers. Before discussing the results of this study, it should be emphasized that the study was carried out on a small sample of patients, so the findings must be considered preliminary. From our results, the prevalence of total OMLs was higher among ECs consumers, but the difference between the two groups was not statistically significant. One of the most com- mon lesions in both groups was smoker’s melanosis and this was consistent with the observations made by Saraswathi et al. [11] and Hedin et al. [12]. Polycyclic amines such as nicotine and benzopyrenes, present in tobacco, can activate the production of melanin by melanocytes, perhaps as a pro- tective mechanism of the oral mucosa against tobacco agents. Tobacco-associated melanin pigmentation has been reported in about 22% of smokers and is dose-dependent. In our study, the prevalence of such pigmentation was we found no difference between the former tobacco smokers and the EC consumers, confirming that former smokers have a lower incidence of melanosis [13], as the cessation of tobacco usage can be sufficient in reducing or eliminating the pigmentation. Table 1. Demographic characteristics of the group A (former smokers) and of the group B (EC consumers). Group A (n ¼ 45) Group B (n ¼ 45) Gender Male 22 41 Female 23 4 Mean age 47 þ 11 47 þ 10 Systemic diseases 16 23 Diabetes 3 5 Hypertension 9 7 Heart disease 2 6 HCV 2 5 Table 2. Distribution of OMLs in the group A (former smokers) and in the group B (EC consumers). Oral mucosal lesions Group A (45) n (%) Group B (45) n (%) OR (95% CI) p Value Melanosis 5 (11.1) 6 (13.3) 1.23 .74 Nicotine stomatitis 1 (2.2) 6 (13.3) 6.77 .04 Hairy tongue 1 (2.2) 7 (15.5) 8.11 .02 Hyperplastic candidiasis 2 (4.4) 8 (17.7) 4.65 .04 Median rhomboid glossitis 3 (6.6) 4 (8.8) 1.37 .69 Lichen planus 2 (4.4) 0 0 .15 Erythematous candidiasis 2 (4.4) 4 (8.8) 2.1 .39 Leukoplakia 2 (4.4) 1 (2.2) 2.05 .55 Hyperkeratosis 2 1 Dysplasia 0 0 Squamous cell carcinoma 1 (2.2) 0 (0) 0 .31 Total 19 36 0.42 .28 Significant, p value .05. ACTA ODONTOLOGICA SCANDINAVICA 227
  • 4. Regarding other OMLs, nicotine stomatitis occurred more frequently in 6/45 EC consumers and only in 1/45 former smokers (p ¼ .04). The many irritants, toxins and carcinogens, found naturally in tobacco, cause the typical opacification or keratinization of the palate seen as red dots surrounded by white keratotic rings [14]. Although ECs do not contain as many ingredients as conventional tobacco, they are vapor- ized by heat starting from a liquid solution (a mixture of pro- pylene glycol, glycerine, nicotine and flavouring) [15]. The nicotine content in ECs varies widely among brands, typically ranging from 0 to 34 mg/ml [16]. Emissions from ECs may also contain fine particles of flavours, aroma transporters, gly- cerol, propylene glycol, nicotine, trace amounts of carcino- gens, heavy metals and other chemicals [1]. We can speculate that nicotine stomatitis in ECs consum- ers may depend not only on the exposure of the palatal mucosa to nicotine but also to some of these chemical com- pounds. For instance, a recent study found that the product characteristics of electronic nicotine delivery systems, includ- ing flavouring, might induce inhalation toxicity, with a straw- berry-flavoured product being the most cytotoxic [17]. Likewise, we can also interpret the high percentage of hyperplastic candidiasis in the retrocommissural area (17.8%) found in the group of ECs consumers (p ¼ .04). Many cross- sectional studies show a higher prevalence of hyperplastic candidasis among smokers while there are no data about ECs consumers. Candidal ability to invade superficial layers of the epithelium, aided by their hyphal appendages with tips con- taining concentrated amounts of candidal proteinases (secreted aspartyl proteinases [SAP]) and lipases – is optimal at acidic pH. Several studies have shown that many protect- ive salivary proteins such as lactoferrin, lactoperoxidase, and immunoglobulins, especially IgA1 and IgA2, are susceptible to degradation by candidal SAPs. We can presume that hyperplastic candidiasis in ECs consumers could be favoured by a pH alteration induced by the aforementioned chemical compounds [18]. Hairy tongue resulted in a statistically greater prevalence among EC consumers than in former smokers. There are numerous initiating or predisposing factors for the abnormal coating on the dorsal surface of the tongue, particularly with smoking-associated pH changes [14]. We can speculate that the mucosal changes may also arise from other factors, i.e. the mucosal drying effects, the high intraoral temperatures, intraoral pH changes, local alteration of membrane barriers and immune responses, or altered resistance to fungal and viral infections. No differences in terms of precancerous OMLs (lichen pla- nus, leukoplakia) were found between the two groups. Only one case of squamous cell carcinoma was found on the lat- eral surface of the tongue in a 52-year-old former smoker. Our results show that e-cigarettes are linked to three types of inflammatory lesions in the oral cavity. Future case- control or cohort studies for individual lesions with larger sample sizes are necessary to evaluate the risk for OMLs resulting from EC habits. Disclosure statement No potential conflict of interest was reported by the authors. References [1] Grana R, Benowitz N, Glantz SA. E-cigarettes: a scientific review. Circulation. 2014;129:1972–1986. [2] Kim KH, Kabir E, Jahan SA. Review of electronic cigarettes as tobacco cigarette substitutes: their potential human health impact. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2016;34:262–275. [3] Goniewicz ML, Knysak J, Gawron M, et al. Levels of selected carci- nogens and toxicants in vapour from electronic cigarettes. Tob Control. 2014;23:133–139. [4] Misra M, Leverette RD, Cooper BT, et al. Comparative in vitro tox- icity profile of electronic and tobacco cigarettes, smokeless tobacco and nicotine replacement therapy products: e-liquids, extracts and collected aerosols. Int J Environ Res Public Health. 2014;11:11325–11347. [5] Shen Y, Wolkowicz MJ, Kotova T, et al. Transcriptome sequencing reveals e-cigarette vapor and mainstream-smoke from tobacco cigarettes activate different gene expression profiles in human bronchial epithelial cells. Sci Rep. 2016;6:23984. [6] Scheffler S, Dieken H, Krischenowski O, et al. Evaluation of e-cigar- ette liquid vapour and mainstream cigarette smoke after direct exposure of primary human bronchial epithelial cells. Int J Environ Res Public Health. 2015;12:3915–3925. [7] Kramer IR, Pindborg JJ, Bezroukov V, et al. Guide to epidemiology and diagnosis of oral mucosal diseases and conditions. World Health Organization. Community Dent Oral Epidemiol. 1980;8:1–26. [8] Food And Drug Administration, Public Health Service, U.S. Department Of Health And Human Services. Shared risk evalu- ation mitigation strategy for all immediate-release transmucosal fentanyl dosage forms. J Pain Palliat Care Pharmacother. 2012; 26:123–126. [9] Franco T, Trapasso S, Puzzo L, et al. Electronic cigarette: role in the primary prevention of oral cavity cancer. Clin Med Insights Ear Nose Throat. 2016;9:7–12. [10] Reuther WJ, Hale B, Matharu J, et al. Do you mind if I vape? Immediate effects of electronic cigarettes on perfusion in buccal mucosal tissue: a pilot study. Br J Oral Maxillofac Surg. 2016;54: 338–341. [11] Saraswathi TR, Ranganathan K, Shanmugam S, et al. Prevalence of oral lesions in relation to habits: cross-sectional study in South India. Indian J Dent Res. 2006;17:121–125. [12] Hedin CA, Pindborg JJ, Ax ell T. Disappearance of smoker’s melan- osis after reducing smoking. J Oral Pathol Med. 1993;22:228–230. [13] Ax ell T, Hedin CA. Epidemiologic study of excessive oral melanin pigmentation with special reference to the influence of tobacco habits. Scand J Dent Res. 1982;90:434–442. [14] Regezi J, Sciubba J, Jordan R. Oral pathology. 7th ed. Elsevier; 2016. p. 86. [15] Cheng T. Chemical evaluation of electronic cigarettes. Tob Control. 2014;23(Suppl 2):ii11–ii17. [16] Goniewicz ML, Kuma T, Gawron M, et al. Nicotine levels in elec- tronic cigarettes. Nicotine Tob Res. 2013;15:158–166. [17] Leigh NJ, Lawton RI, Hershberger PA, et al. Flavouring signifi- cantly affect inhalation toxicity of aerosol generated from elec- tronic nicotine delivery systems (ENDS). Tob Control. 2016; 25(Suppl 2):ii81–ii87. [18] Sitheeque MAM, Samaranayake LP. Chronic hyperplastic candido- sis/candidiasis (candida leukoplakia). Crit Rev Oral Biol Med. 2003;14:253–267. 228 E. BARDELLINI ET AL.