Effect of Tobacco in oral mucosa

1. TOBACCO INDUCED ORAL
MUCOSAL LESIONS
By Ahmed Saleem

2. WHAT IS TOBACCO?
• Tobacco is a plant originally indigenous to the
Americas which is now grown across the world. Its
leaves contain high levels of the addictive chemical
nicotine and many cancer-causing chemicals, especially
polyaromatic hydrocarbons (PAHs).
•The leaves may be smoked (in cigarettes, cigars, and
pipes), applied to the gums (as dipping and chewing
tobacco), or inhaled (as snuff).
•Tobacco use and exposure to second-hand tobacco
smoke causes many types of cancer, as well as heart,
respiratory, and other diseases.

3. HARMFUL CHEMICALS IN
TOBACCO PRODUCTS
1.Tobacco smoke
 Tobacco smoke is made up of thousands of chemicals, including at least 70
chemicals known to cause cancer
 Some of the chemicals found in tobacco smoke include:
1. Hydrogen cyanide
2. Formaldehyde
3. Lead
4. Arsenic
5. Ammonia
6. Benzene
7. Carbon monoxide
8. Tobacco-specific nitrosamines (TSNAs)
9. Polycyclic aromatic hydrocarbons (PAHs)
10. Radioactive elements, such as polonium-210
 Most of the substances come from the burning tobacco leaves themselves, not from
additives included in cigarettes .
(American Cancer Society)

4. RADIOACTIVE MATERIALS IN TOBACCO
SMOKE
Radioactive materials are in the tobacco leaves come from the fertilizer
and soil used to grow the tobacco leaves, so the amount in tobacco
depends on the soil the plants were grown in and the type of fertilizers
used.
These radioactive materials are given off in the smoke when tobacco is
burned, which smokers take into their lungs as they inhale, and this may
be more associated smokers getting lung cancer.
(American Cancer Society)

5. SMOKELESS
TOBACCO
PRODUCTS
•Smokeless tobacco products contain a variety of potentially harmful
chemicals, including high levels of Tobacco-specific nitrosamines (TSNAs).
•There are also other cancer-causing agents in smokeless tobacco, such as
polonium-210 (a radioactive element) and other polycyclic aromatic
hydrocarbons (PAHs).
•These carcinogens are absorbed through the mouth and may be why several
types of cancer are linked to the use of smokeless tobacco.
•On average, smokeless tobacco products kill fewer people than cigarettes. But
while they're often promoted as a less harmful alternative to smoking, some
types have still been linked with cancer.
•No smokeless tobacco product has been proven to help smokers quit.
(American Cancer Society)

6. E-CIGARETTES AND
SIMILAR DEVICES
E-cigarettes and other electronic nicotine delivery systems (ENDS)
have become very popular in recent years, especially among
younger people.
Makers of e-cigarettes and other electronic nicotine delivery
systems (ENDS) often claim the ingredients are safe. But the
aerosols that these products produce can contain nicotine,
flavourings, and a variety of other chemicals, some known to be
toxic or to cause cancer.
The levels of many of these substances appear to be lower than in
traditional cigarettes, but the amounts of nicotine and other
substances in these products can vary widely because they are not
standardized.
The long-term health effects of these devices aren't yet known.
(American Cancer Society)

7. • People can smoke, chew, or sniff
tobacco.
1. Smoked tobacco products include cigarettes,
cigars, bidis, and kreteks. Some people also
smoke loose tobacco in a pipe or hookah (water
pipe).
2. Chewed tobacco products include chewing
tobacco, snuff, dip, and snus; snuff can also be
sniffed.
• Tobacco consumption also remains the
most important avoidable risk factor for
oral cancer.
• Tobacco related cancers account for
nearly 50% of all cancers in men and 25%

8. PREVALENCE
•Children: Approximately 43 million
children (aged 13-15) used tobacco in
2018 (14 million girls and 29 million
boys).
•Globally, 942 million men and 175 million
women ages 15 or older are current
smokers.
•Most gains are being made in low- and
middle-income countries.
•WHO’s South East Asian Region has the
highest rates of tobacco use, of more
than 45% of males and females aged 15
years and over.

10. TOBACCO INDUCED ORAL
MUCOSAL LESIONS
•Long term contact of tobacco
with the oral mucosa induces
variety of changes which could
be due to the carcinogen itself or
as a protective mechanism of the
oral cavity.
• These changes could be
categorized as tobacco induced
oral mucosal lesions which are
less likely to cause cancer,
lesions that are potentially
malignant and tobacco induced
malignancies.

11. TOBACCO INDUCED
NON-NEOPLASTIC ORAL
MUCOSAL LESIONS

12. BETEL CHEWER’S
MUCOSA
•Betel chewer’s mucosa was first described in 1971 by
(Mehta et al).
•It is a clinical appearance, which characterised by a
brownish‐red discolouration of the oral mucosa with an
irregular epithelial surface that has a tendency to
desquamate or peel off.
•The lesion might occur at the site of quid placement
(buccal mucosa), because of either the direct action of quid
or traumatic effect of chewing or both with a tendency for
the oral mucosa to desquamate or peel.
•The underlying areas assume a pseudomembranous or
wrinkled appearance.
•The bright red colour produced by betel chewing is due to
the formation of O-quinone from the water-soluble
polyphenols notably leucocyanidins at alkaline pH of 8 to 9
via secondary reactions.

13. •The prevalence of Betel chewer’s mucosa varies between 0.2%
and 60% in different studies from South and Southeast Asia.
•Women are more frequently affected than men.
•Betel chewer's mucosa may be found together with other oral
mucosal lesions such as leukoedema, leukoplakia and
ulceration

14. The histological features are characteristic: The epithelium is often
hyperplastic, and brownish amorphous material derived from the
betel quid may be demonstrated not only on the epithelial surface but
also intra‐ and inter ‐cellularly +Ballooning of epithelial cells may
occur. .
Betel chewer's mucosa is most likely not associated with oral cancer.
Differential diagnoses include: cheek biting, with which it has a
number of similarities, and other predominantly white lesions that
may have taken up stains from tobacco and other substances.

15. LEUKOEDEMA
Leukoedema is a chronic white mucosal
condition in which the oral mucosa has a grey
opaque appearance, and when the mucosa is
stretched the lesions disappear and reappear
on releasing the mucosa.
It develops due to piling of spongy cells.
Leukoedema is the normal anatomic variant of
the oral mucosa which has clinical appearance
similar to potentially malignant white lesions
such as leukoplakia and lichen planus. Other
lesions which closely mimic leukoedema are
white sponge nevus and cheek bite.
Its association with smoking habit is unclear.

16. HISTOPATHOLOGICA
L EXAMINATION:
• reveals hyper parakeratosis and acanthosis of
surface epithelium.
• Cells of the spinous layer show intracellular
oedema, cells appear pale and have pyknotic
nucleus.
• No dysplastic features were observed.

17. NICOTINE STOMATITIS
•Smoker’s palate is also known as leukokeratosis nicotina
palate, Nicotine Stomatitis, Smoker's Palate, Smoker's
Keratosis, Smoker's
Patch) and is a common reaction of palatal mucosa to
smoking.
•Clinically the lesion appear as diffuse white patch with
numerous excrescences having central red dots
corresponding to minor salivary gland ducts.
•Nicotinic Stomatitis is been associated with pipe, cigarette,
and cigar smoking, and, rarely, with chronic ingestion
of high-temperature liquids (these changes are observed
most often in pipe and reverse cigarette smokers and less
often in cigarette and cigar smokers).
•Generally, it is asymptomatic or mildly irritating, Patients
typically report that they are either unaware of the lesion or
have had it for many years without changes.

18. • Nicotinic Stomatitis first becomes
visible as a reddened area and slowly
progresses to a white ( cannot be wiped
off), thickened, and fissured
appearance.
• The roof of the mouth has numerous
minor salivary glands, they become
swollen, and the orifices become
prominent, giving the tissue a speckled
white and red appearance.

19. •The mechanism of action is heat irritation from a tobacco product
that acts as a local irritant, stimulating a reactive process (In patients
who wear dentures often protect the palate from these irritants).
•Management:
•Nicotinic Stomatitis generally is a reversible lesion once the irritant
(that is, smoking) is removed.
The prognosis is excellent.

20. LICHENOID LESIONS
Lichenoid lesions grossly resemble oral lichen planus but
have certain specific differences:
The lesion is characterized by the presence of fine, white,
wavy parallel lines that do not overlap or criss-cross, is not
elevated and in some instances radiate from a central
erythematous area.
The lesion generally occurs at the site of quid placement.
Some 89% of the lesions occur among betel quid chewers
and 11% among those who chewed pan and smoked tobacco.
Most of these lesions remain stationary or sometimes regress
on discontinuance of the habit thereby requiring no further
treatment.
Sufficient epidemiological data is unavailable regarding this
lesion.

21. DIFFERENCE BETWEEN CLASSIC
LICHEN PLANUS
AND LICHENOID LESION
LICHEN PLANUS LICHENOID LESION
Age Mean age 50 years Mean age 66 years
Site Intra+ extra orally Associated with the cause
Histology Comact hyperkeratosis
Wedge shaped hypogranulosis
Irregular acanthosis
“saw-toothing” of rete ridges and vascular damage to the
basal layer.
A dense band like infiltration of lymphocytes.
Focal parakeratosis and focal
absence of granular layer
Colloid bodies are more numerous
and are present higher up in the
epidermis.
The interface infiltration is less
dense and more pleomorphic with
abundant plasma cells and
eosinophils.
Treatment First line corticosteroid Withdrawal of the cause.

22. ORAL PIGMENTATION (SMOKER’S
MELANOSIS)
Oral pigmentation secondary to smoking may occur occurs as
diffuse pigmentation at any site with increased tendency to affect
facial gingiva.
The frequency of the lesions increases with heavy usage of cigarette
smoke. Different studies show prevalence rates of 3.5%,1.14%, 2.3%
and 4.17%. But most of the studies have reported smokers’
melanosis as the most frequently encountered oral mucosal lesion.
Aetiology and Pathogenesis: It has been suggested that melanin
production in the oral mucosa of smokers serves as a protective
response against some of the harmful substances in tobacco
smoke.
Clinical features: It occurs as diffuse pigmentation frequently.
Diagnosis: is made based on the clinical appearance and history of
tobacco use.
Management: There is no specific treatment for the condition,
cessation of smoking usually resolves the pigmentation with time.

23. TOBACCO INDUCED
POTENTIALLY
MALIGNANT

24. LEUKOPLAKIA
• Leukoplakia defined by WHO as a
predominantly white lesion or plaque
affecting the oral mucosa that cannot be
characterized clinically or histopathologically
as any other disease and is not associated
with any other physical or chemical agents
except tobacco.
•The prevalence of oral leukoplakia= 2%
• Leukoplakia is 6 times more common in
tobacco user in compare to non-users.

25. Homogeneous:
(predominantly white lesion of
uniform flat, thin appearance that
may exhibit shallow cracks and that
has a smooth, wrinkle do corrugated
surface with a consistent texture
throughout )
Non-homogeneous leukoplakia :
defined as a predominantly white or
white-and-red lesion (‘‘erosive
leukoplakia’’; ‘‘erythro-
leukoplakia’’) that may be either
irregularly flat, nodular (‘‘speckled’’)
or verrucous.

26. LEUKOPLAKIA IS THE TERM USED TO RECOGNIZE WHITE
PLAQUES OF QUESTIONABLE RISK HAVING EXCLUDED
OTHER KNOWN DISEASES OR DISORDERS ?

27. MANAGEMENT
OF
LEUKOPLAKIA
• A biopsy is mandatory, and
the definitive diagnosis is
made when any etiological
cause other than
tobacco/areca nut use has
been excluded and
histopathology has not
confirmed any other specific
disorder.
• Leucoplakia is considered as a
potentially malignant disorder
with a malignancy conversion
rate ranging from 0.1% to
17.5%.
(Carrard & van der Waal,
2018)

28. ERYTHROPLAKIA.
(HOLMSTRUP, 2018)
• Erythroplakia is an uncommon but severe form of a
potentially malignant lesion, defined by WHO as “any
lesion of the oral mucosa that presents as bright red
velvety plaques which cannot be characterized
clinically or histopathologically as any other
recognizable condition”
• According to the American Academy of Oral
Medicine, Erythroplakia and leukoplakia are
generally considered precancerous (or potentially
cancerous) lesions.
• the most common site affected is mucosal surfaces
of the soft palate, the floor of the mouth, and
the buccal mucosa.
(Shafer and Waldron ) reported gender-related differences in
terms of the mucosal sites affected; these investigators indicated
that the most common site of occurrence of erythroplakia in men
was the floor of the mouth, while in women, the combined
mandibular alveolar mucosa, mandibular gingiva, and mandibular
sulcus were most affected sites .
Clinically, the lesion is thereby easily distinguishable from other red
lesions of the oral mucosa including (Atrophic lichen planus lesions

29. PREVALEN
CE
There appear to be few data available on the
prevalence of oral erythroplakia, and most data are
established in selected groups of individuals
including hospital associated populations and
samples of individuals with special habits.
Most of the studies with epidemiologic data
concerning oral erythroplakia were conducted in
India and Southeast Asia, indicating prevalence
rates of 0.02% to 0.83%, with the majority
occurring in older individuals (sixth and seventh
decades).
• A clinical hospital- based study of 500 patients (only one
woman), all of whom were habitual psychoactive substance
users, showed a prevalence of 0.6% ( Thavarajah et al., 2006),
and the prevalence is almost similar (0.7%) among 559 tobacco
users (25% women) in Saudi Arabia (Al-Attas, Ibrahim, Amer,
Darwish Zel, & Hassan, 2014), but among 210 addiction
treatment centre residents (30% women) in southern Ireland, as
1.9% (O’Sullivan, 2011).
• In general population samples outside the hospital
environment, the prevalence is found to be lower. Among 1241
individuals (47.1% women) in India, the prevalence of
erythroplakia was 0.24% (Kumar et al., 2015), and a similar
prevalence (0.3%) was found among 1385 rural Brazilian
workers, of which 53.2% were females (Ferreira et al., 2016).

30. MANAGEMENT
Definitive treatment is by surgical excision, because it reduces malignant transformation but does not
totally eliminate the risk.
(In recent years, studies on the use of topical 5-aminolevulinic acid-mediated photodynamic therapy
for oral erythro-leukoplakia have shown that this specific treatment exhibited partial to complete
response after an average of three to six treatments. Still, neither long-term follow-up nor long- term
results are provided. (Schmidt-Westhausen, 2017)
It is well established that premalignant lesions may recur after surgical removal (Holmstrup et al.,
2006; Lumerman, but cases of reversible erythroplakia have also been observed in a longitudinal study
in which some lesions resolved without no treatment being offered (Holmstrup et al., 2006).
Malignancy rates from 14% to 50% (Reichart & Philipsen, 2005).
Unfortunately, there is currently no reliable diagnostic tool to identify exactly those lesions that will progress
to cancer and to obtain the best possible prognosis, patients with the lesions mentioned (sharply demarcated
fiery red lesions situated at a slightly lower level) should therefore be followed intensely at short intervals
independent of possible relation to other diseases or irritants

31. PALATAL CHANGES AMONG
REVERSE SMOKERS
Palatal changes secondary to reverse chutta smoking can be
categorized as palatal keratosis, excrescences, patches, red areas,
ulceration and pigmentation changes.
These changes are seen in up to 46% of reverse smokers and carry
increased tendency for malignant transformation (No enough
epidemiological data exist regarding the prevalence of these
changes).

32. ORAL SUBMUCOUS FIBROSIS
OSMF as a potentially malignant disease was first described in 1950’s with
increased tendency to affect people of Asian descent.
It is a chronic disorder characterized by fibrosis of the lining mucosa of the
upper digestive tract involving the oral cavity, oro-and hypopharynx and the
upper third of oesophagus.
The fibrosis involves the lamina propria and the submucosa and may extend
into the underlying musculature resulting in the deposition of dense fibrous
bands, resulting in limited mouth opening.
Areca nut has been proved to be the single most important etiological factor
responsible for OSMF.
The pre-cancerous nature was first described by (Paymaster) in 1956 that
was later confirmed by various studies.
A malignant transformation rate was shown to be in the range of 7 to 13%
and (transformation rate of 7.6% was reported in cohort study)

33. LICHEN PLANUS
•Lichen planus is a mucocutaneous disorder affecting the skin and
mucous membrane with increased potential for malignant
transformation.
•The condition most commonly affects individuals in the 5th to 6th
decade although younger individuals are also affected and is twice
more common in women than in men.
•The malignant potential of lichen planus has been a subject of
intense research with studies showing malignant transformation in
the range of 0 to 12.5% (Other reports put the overall prevalence rate
at 0.5 to 2.2%).

34. •The clinical features present as reticular, papular, plaque-like (hyperkeratotic variants) and
erythematous, ulcerative, erosive, as well as bullous (erosive variants) forms. The reticular
alteration has a web-like appearance and is the most common form (Wickham striae).
•OLP generally affects both sides of the buccal mucosa, frequently involving the tongue,
gingiva, oral vestibule, or multiple locations of the oral mucosa, whereas manifestations
on the palate are rare.
•In most cases, the clinical manifestations of OLP are sufficient for establishing the
diagnosis, although a biopsy is recommended to confirm the clinical diagnosis and to
exclude the presence of dysplasia or malignancy.
•Persistent erosive and plaque-like variants, especially involving the tongue, have a greater
malignant potential.
•Symptomatic OLP is a painful condition and complete remission is rare.
•The symptomatic forms of OLP include the erosive, ulcerative, bullous, and erythematous
variants (which manifest with symptoms such as a burning sensation and a considerable
interference with food intake and daily oral hygiene).

35. TOBACCO INDUCED
MALIGNANCIES

36. ORAL SQUAMOUS CELL
CARCINOMA :
Oral squamous cell carcinoma (OSCC) is a multifactorial disease with tobacco
and alcohol being the major risk factors.
Squamous cell carcinoma is defined by (Pindborg et al, 1997) as malignant
epithelial neoplasm exhibiting squamous differentiation as characterised by
the formation of keratin and/or the presence of intercellular bridges.
Oral and pharyngeal cancer grouped together is the 6th common cancer in
the world.
With an estimated incidence is around 2,75,000 (with two-thirds of the
cases occurring in developing countries).
OSCC affects men more than women which would be attributed to heavier
use of risk factors by men (However, the ratio of males to females has
declined over the years with cases being increasingly reported in women).
Tongue seems to be the predominant site affected in Western countries, but
in some area like India, alveolo-buccal complex is mainly affected due to
tobacco chewing habit.

37. ETIOLOGY
1. Smoking of cigarettes, cigars, and pipes
2. Use of smokeless tobacco: snuff and chewing tobacco
3. Drinking of 3 ounces or more of ethanol per day
4. Smoking and ethanol (highest risk)
5. Betel nut
6. Age over 40 years
7. High accumulation of x-irradiation over the years
8. Previous history of oral cancer
9. Infection with human immunodeficiency virus and other immunosuppression
conditions
10. Ethnic or family history
11. Mouth rinse with a significant alcohol content?
12. Chronic mechanical irritation?
13. Poor oral hygiene?
14. Candida infection?

38. MANIFESTA
TION
• Rapid proliferation/growth of long standing.
• Unexplained colour change.
• Growth / ulceration of pigmented area.
• Ulceration / erosion in otherwise.
• Homogenous white/red lesions.
• Longstanding ulcers with areas of sharp tooth or appliances
insult.
• Induration in / around ulcer.
• Unexplained mobility, exfoliation of teeth.
•Unexplained paraesthesia.
•Unexplained dysphagia, hoarseness of voice.
•Unexplained restriction of tongue movements.
•Pain in ear.
•Rapid enlargement of lymph nodes.

39. TNM STAGING OF ORAL CANCER
The tumor-node-metastasis (TNM) staging system was first reported
by pierre denoix in the 1940s.
Objective:
•To aid the clinician in treatment planning
•To provide prognostic value
•To evaluate the results of treatment
•To facilitate exchange of information between surgical teams
•To contribute to the continuing investigation of human cancer.

40. T: TUMOUR SIZE
TX - Primary tumor cannot be assessed
T0 - No evidence of primary tumor
Tis - Carcinoma in situ
T1 - Tumor 2 cm or less in greatest dimension
T2 - Tumor more than 2 cm but not more than 4 cm in greatest
dimension
T3 - Tumor more than 4 cm in greatest dimension

41. T4a - Lip tumor invades through cortical bone, inferior alveolar
nerve, floor of mouth, or skin of face (ie, chin or nose)*
oral cavity tumor invades through cortical bone, into deep [extrinsic]
muscle of tongue (genioglossus, hyoglossus, palatoglossus, and
styloglossus), maxillary sinus, or skin of face.
T4b - Tumor involves masticator space, pterygoid plates, or skull
base and/or encases internal carotid artery

42. LYMPH NODE METASTASIS
• Nx - Regional lymph nodes cannot be assessed
• N0 - No regional lymph node metastasis
• N1 - Metastasis in a single ipsilateral lymph node, 3 cm or less in
greatest dimension
• N2 - Metastasis in a single ipsilateral lymph node, more than 3 cm
but not more than 6 cm in greatest dimension; or in multiple
ipsilateral lymph nodes, none more than 6 cm in greatest dimension;
or in bilateral or contralateral lymph nodes, none more than 6 cm in
greatest dimension

43. N2a Metastasis in a single ipsilateral lymph node more than 3 cm but
not more than 6 cm in greatest dimension.
• N2b Metastasis in multiple ipsilateral lymph nodes, none more than
6 cm in greatest dimension
• N2c Metastasis in bilateral or contralateral lymph nodes, none more
than 6 cm in greatest dimension.
• N3 metastasis in a lymph >6cm in greatest dimension.

44. M: DISTANT METASTASIS
• Mx Distant metastasis cannot be assessed. • M0 No distant
metastasis.
• M1Distantmetastasis.

45. PREVENTION
Secondary prevention mainly aims at the early diagnosis of cancer/pre-
cancer and initiate treatment at an early stage to prevent further
progression. Currently no standardized methods or practices exist for early
detection of oral cancer although several diagnostics aids are being
constantly evaluated (Simple oral visual examination with adequate light is
followed on a regular basis and is considered as a fairly good screening
method for early detection of oral mucosal lesions).
additional screening aids are needed which can be employed along with oral
visual examination.
Research is underway in this aspect but till date no technique has provided
definite evidence to suggest that it improves the sensitivity or specificity of
oral screening beyond conventional oral examination alone.
These diagnostic tests include: (toluidine blue staining, brush cytology,
tissue reflectance (Vizilite plus), narrow emission tissue fluorescence which
are light based detection systems and use of tumor markers for early
diagnosis.

46. INTERVENTION
Tertiary care of OSCC mainly aims in surgically removing the tumor
mass along with chemotherapy and radiotherapy followed by
palliative care and post-operative follow-up to reduce morbidity.
Surgical management involves the removal of tumor mass and neck
dissection in case of cervical metastasis.
Recent studies have explored targeted molecular treatment with trials
underway for epidermal growth factor, insulin like growth factor
receptor, C-Met and inducers of apoptotic markers.

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