2. Epidemiological studies have documented a high incidence of
oral cancer in India and some south-east Asian countries21.
According to the Indian Council of Medical Research about
200,000 cases of cancer of the oral cavity are seen every year
in India. Estimates based on weighted averages of data from
Bangalore, Mumbai, Bhopal, Chennai, and Delhi show that
carcinoma of the oral cavity has an incidence of 4.0% of all
malignancies in males and 3.5%of all malignancies in females
(Tables 1 and 2).
Due to its relatively prolonged course, it is estimated that its
prevalence is around 12% of all malignancies in males and 10
% of all malignancies in females. The age-adjusted incidence
rate of oral cavity carcinoma is 25 per 100,000 in India.
Table 1 : Incidence of Buccal Mucosa Cancer
(% of all malignancies)
Registry Males Females M:F ratio
Delhi 1.49 0.58 2.6
Bhopal 6.72 3.0 2.24
Chennai 6.05 4.48 1.25
Bangalore 1.86 6.57 0.28
Mumbai 3.66 2.65 1.6 Worldwide,
3. as well as in India there has been a steady increase in the
incidence of cancer of the oral cavity. The male to female
ratios are decreasing worldwide (Table 3) probably due to the
rise in use of tobacco products and alcohol by women. In India
tobacco related cancers account for almost half of the total
cancers in men and one fourth in women. Oral cancer
accounts for a third of these with 90% being tobacco chewers.
The high incidence of this cancer in Indian women is probably
because the prevalence of tobacco chewing is more or less
equal between the sexes13. The high incidence of buccal
mucosal cancer in India is also probably a consequence of
tobacco chewing and usage of a ‘quid’. Studies have reported
a high incidence of this cancer in people of Indian descent
settled in South Africa6 and in Malaysia22. Even in these
populations, the incidence among females of Indian origin is
much higher than the native populations. Whether this is a
reflection of ingrained habits and customs or due to genetic
susceptibility is not clear.
RISK FACTORS
4. Tobacco and alcohol have consistently been associated
with cancers of the oral cavity. Buccal mucosal cancer in
India is associated predominantly with the habit of tobacco
chewing especially the type endemic to this country.
Tobacco Consumption in India : Only 20% of the tobacco
consumed in India is in the form of cigarettes. Bidis account
for 40% of tobacco consumption with the rest divided among
chewing tobacco, pan masala, snuff, hookah, hookli, chutta,
dhumti, and other tobacco mixtures featuring ingredients such
as areca nut. Buccal mucosal cancer is related to the use of
smokeless tobacco. Smokeless tobacco is in common usage
in this country in various forms17. Pan chewing is widely
practiced in India. Also known as betel quid, it consists of
tobacco, areca nuts, and slaked lime wrapped in a leaf.
Various types of tobacco are used in pan. Like zarda,
pattiwala, kiwam, mishri and pills. Some variants of pan
include pan masala, mainpuri, and mawa. Khaini is a mixture
of tobacco and slaked lime which is left in the lower
gingivolabial sulcus for a prolonged time19. Studies have
shown that keeping a tobacco quid in the cheek pouch
5. overnight increases the risk of buccal mucosal cancer4,5,16.
Also the addition of lime increases the carcinogenicity of
tobacco by alkalinisation which leads to differences in the
composition & concentration of mutagens from tobacco17.
Some of these mutagens that have been identified positively
are tobacco specific N-nitrosamine (TSNA), N’-
nitrosonorcotine (NNN) and 4(methylnitrosamino)-1-(3-
pyridyl)-1-butanone (NNK) being the most important7. Also,
reactive oxygen species and OH` radical formed from
polyphenolic betel quid ingredients and lime at alkaline pH
have been implicated as the agents responsible for DNA and
tissue damage. These agents are formed in vitro in the
presence of extracts of areca nut and catechu, transition metal
ions such as Cu 2+ and Fe 2+ and lime or sodium
carbonate15.
Table 2 : Buccal mucosa cancer - Cumulative risk (%)
6. Registry Sex 0-14 y 15-34 35-69 0-64 y 0-74 y
y y
Delhi M 0.00 0.00 0.22 0.19 0.30
F 0.00 0.01 0.15 0.12 0.16
Bhopal M 0.00 0.03 0.86 0.55 1.03
F 0.00 0.00 0.60 0.49 0.60
Chennai M 0.00 0.00 0.60 0.44 0.74
F 0.00 0.02 0.59 0.44 0.74
Mumbai M 0.00 0.00 0.35 0.25 0.42
F 0.00 0.00 0.25 0.18 0.31
Bangalore M 0.00 0.00 0.19 0.15 0.25
F 0.00 0.01 0.74 0.58 0.86
Table 3 : Cancer of the lip and oral cavity in other regions
of the world
Country Incidence (per M:F
100000) ratio
England & 2.8 1.7
Wales
South 8.06 4.1
Africa
Norway 2.1 1.2
U.S.A. 3.1 2.0
India 25.0 1.6
7. Human Papilloma Virus : HPV has been consistently isolated
in an abnormally high percentage of Indian patients of cancer
of the oral cavity. The habit of betel chewing is thought to play
a role in the etiology of this disease. The prevalences of
HPV-6, HPV-11, HPV-16 and HPV-18 were 13%, 20%, 42%
and 47% respectively. Though these studies show that HPV
has probably a role in the mutagenecity of betel, the evidence
at present is purely circumstantial2,16,21.
Genetic Alterations: Alterations in p53 and p16 are common
in tumours from the West (47%) but are uncommon in the
East (7%). The tumours from India and South Asia are
characterised by the involvement of ras oncogenes, including
mutations loss of heterozygosity (H-ras), and amplification (K-
and N-ras), events which are uncommon in the West. There is
a possibility that these genetic differences reflect aetiology
and/or ethnic origin4,8,18.
Nutritional Status : Various studies have shown that
modulators of epithelial differentiation like vitamins A, E and
beta carotene are protective for oral cancers and are capable
8. of reversing premalignant changes like leukoplakia3,20.
Submucous Fibrosis : Oral submucous fibrosis is a
precancerous condition of the mouth that is strongly
associated with chewing areca nuts. It is reported to occur
more frequently among women rather than men. Aetiologies
that have been proposed include stimulation of collagen
production and decreased activity of collagenase due to
various components of areca nut such as arecoline and
tannins. Symptoms of submucous fibrosis include localized
burning and intolerance to spicy food, followed by blanching
and ulceration of the mucosa and the formation of
characteristic fibrous bands These bands form bilaterally,
initially in the fauces and then in the buccal ands labial areas.
As the disease progresses the bands on either side meet on
the floor and the roof of the mouth forming a fibrous ring. The
diagnosis of this condition is made on clinical grounds and
there are no reports of staging it by severity though a
histological classification has been proposed12.
PATHOLOGY
9. Buccal mucosal cancer is almost invariably squamous cell
carcinoma. Depending on the degree of keratinization, it is
divided into well differentiated (>75% keratinized), moderately
differentiated (25-50% keratinized) and poorly differentiated
(<25% keratinization)10. Probably as a consequence of HPV
having a role in aetiology of buccal mucosal cancer, a large
proportion of Indian patients have verrucous carcinoma2,16,21.
Verrucous carcinoma, also known as Ackerman’s tumour is
well differentiated and is characterized by a cauliflower like
exophytic growth with deep papillary projections and a grey-
white surface. These tumours are slow growing, metastasize
late and offer a better prognosis. They may however
dedifferentiate and metastasize following irradiation10.
CLINICAL FEATURES
Patients of buccal mucosal cancer in India typically belong
to the lower socio-economic strata. They are also younger
than patients in the West by about a decade. These patients
are invariably tobacco or pan chewers with poor oral hygiene
and staining of teeth. Often, submucous fibrosis is also
10. present. Other premalignant lesions such as leukoplakia or
erythroplakia may also be seen alone or in conjunction. The
tumours are seen commonly in the lower gingivolabial sulcus
adjacent to the site where the quid of betel or tobacco is kept
in the mouth1,2. Common early symptoms are pain, itching,
swelling, dull sensation and colour change. These symptoms
are invariably tolerated by the patients, signifying a type of
person who neglects personal care. Thus these patients
mostly present late in the course of their illness with advanced
lesions1 and features like large primary lesion, trismus,
odynophagia, tethering of the tongue, oro-cutaneous fistula,
satellite nodules, and lymph node enlargement. Lymph nodes
when enlarged are of the submandibular group. The upper
deep cervical nodes are usually not involved10.
Conclusion
Though traditionally, and in western textbooks, buccal
mucosal cancer has been clubbed with other oral cancer, it is
in fact a very different entity in terms of epidemiology,
aetiology, pathology and clinical features. Little has been
11. written on buccal mucosal cancer in literature and it is for
Indian researchers to study and throw new light on this
common cancer about which knowledge is so inadequate.
What is evident about the aetiology must form the basis of an
intensive education and awareness campaign to affect a
decrease in the rising incidence of this preventable cancer.
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