BUCCAL MUCOSAL

CANCER

 

Dr.Anil Haripriya 

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, 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 

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

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 (%)

Registry Sex 0-14 y 15-34

y

35-69

y

0-64 y 0-74 y

Delhi M

F

0.00

0.00

0.00

0.01

0.22

0.15

0.19

0.12

0.30

0.16

Bhopal M

F

0.00

0.00

0.03

0.00

0.86

0.60

0.55

0.49

1.03

0.60

Chennai M

F

0.00

0.00

0.00

0.02

0.60

0.59

0.44

0.44

0.74

0.74

Mumbai M

F

0.00

0.00

0.00

0.00

0.35

0.25

0.25

0.18

0.42

0.31

Bangalore M

F

0.00

0.00

0.00

0.01

0.19

0.74

0.15

0.58

0.25

0.86

Table 3 : Cancer of the lip and oral cavity in other

regions of the world

Country Incidence (per

100000)

M:F

ratio

England &

Wales

2.8 1.7

South

Africa

8.06 4.1

Norway 2.1 1.2

U.S.A. 3.1 2.0

India 25.0 1.6

 

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

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 

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 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

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.

.