Epidemiology of Oral Cancer

Contents
Introduction Definitions Classification of Cancer International Classification of disease for oncology Staging of Oral Cancer National Cancer Registry Programme Types of Oral Cancer Clinical Presentations of Oral Cancer Global Scenario of oral cancer Spectrum of oral cancer in India Epidemiological triad Host factors Agent Environmental factors

Diagnosis of Cancer Prevention and control of cancer Role of dentist in detecting and preventing oral cancer Public health approach to oral cancer prevention based on Ottawa charter, WHO, 1986. Global initiatives in the prevention of oral cancer Guide for tobacco cessation Tobacco Control in India: what have we achieved today? World No tobacco day Conclusion References

Introduction
Cancer is one of the most common causes of morbidity and mortality today. In spite of good advancements for diagnosis and treatment, cancer is still a big threat to our society (Kotnis et al, 2005). This is the second most common disease after cardiovascular disorders for maximum deaths in the world (Jemal et al, 2007). 10 million new cancer cases are seen each year worldwide and according to WHO estimates, cancer rates are set to increase at an alarming rate from 10 million in 2000, to 15 million in 2020.
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It accounts for about 23 and 7% deaths in USA and India, respectively. The worlds population is expected to be 7.5 billion by 2020 and approximations predict that about 15.0 million new cancer cases will be diagnosed; with deaths of about 12.0 million cancer patients (Brayand et al, 2006) Nowadays, India is growing with a good progress rate and probably will become a developed country within a few decades resulting into its participation in the world development. Therefore, it is important to study the status of cancers in India so that advance measures may be taken to control this havoc in near future. (Ali I et al, 2011)
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Oral cancer is a major problem in the Indian subcontinent where it ranks among the top three types of cancer in the country. Furthermore, annually almost 7% of all cancer deaths in males and 4% in females have been reported to be due to oral cancers.(Coelho K, 2012)

Oral cancer is of significant public health importance to India. Firstly, it is diagnosed at later stages which result in low treatment outcomes and considerable costs to the patients who typically cannot afford this type of treatment.(P. S. Khandekar et al, 2006) Secondly, rural areas in middle- and low-income countries also have inadequate access to trained providers and limited health services. As a result, delay has also been largely associated with advanced stages of oral cancer. (S. Kumar 2001)
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Thirdly, oral cancer affects those from the lower socioeconomic groups, that is, people from the lower socioeconomic strata of society due to a higher exposure to risk factors such as the use of tobacco. (D. I. Conway, 2008)
Lastly, even though clinical diagnosis occurs via examination of the oral cavity and tongue which is accessible by current diagnostic tools, the majority of cases present to a healthcare facility at later stages of cancer subtypes, thereby reducing chances of survival due to delays in diagnosis.(V. L. Allgar and R. D. Neal, 2005)
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What is cancer? Cancer begins when cells in a part of the body start to grow out of control. There are many kinds of cancer, but they all start because of out-of-control growth of abnormal cells

Origin of the word cancer

The origin of the word cancer is credited to the Greek physician Hippocrates (460-370 BC), who is considered the Father of Medicine. Hippocrates used the terms carcinos and carcinoma to describe non-ulcer forming and ulcer-forming tumors. In Greek, these words refer to a crab, most likely applied to the disease because the finger-like spreading projections from a cancer called to mind the shape of a crab.

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The Roman physician, Celsus (28-50 BC), later translated the Greek term into cancer, the Latin word for crab. Galen (130-200 AD), another Roman physician, used the word oncos (Greek for swelling) to describe tumors. Although the crab analogy of Hippocrates and Celsus is still used to describe malignant tumors, Galens term is now used as a part of the name for cancer specialists oncologists.
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The incidence of head and neck cancer varies enormously all around the world and especially oral cancer which accounts for 3040% of all the malignant tumors in India, being only about 24% in western countries
The FDI recognizes oral cancer as a major public health issue world wide. Oral cancer remains a highly lethal and disfiguring disease. Hence knowing its magnitude, risk factors, presentation, diagnosis and treatment and prevention has become much more important, especially in countries like India.
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Definitions
Neoplasm-is an abnormal mass of tissue, the growth of which exceeds and in an uncoordinated with that of the normal tissue and persist in the same excessive manner after cessation of the stimuli which evoked the change.

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Cancer is defined as a malignant tumour which spreads very rapidly. Carcinoma a malignant tumor occurring in the epithelial tissue and spreading rapidly by direct extension, through the blood circulation or the lymphatic channels and giving rise to secondary metastasis. It may affect any organ or part of the body.

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A premalignant lesion is defined as morphologically altered tissue in which cancer is most likely to develop than in its apparently normal counter part. Leukoplakia, erythroplakia and palatal changes associates with reverse smoking are examples of premalignant lesions. ( WHO) A premalignant condition is a generalized state associated with a significant increased risk of cancer. A premalignant condition can be defined as generalized disturbance or a disease state which predisposes to the development of a neoplasm at a particular site. Syphilis, oral submucosis fibrosis, and lichen planus fall into this category. ( WHO)

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Anaplasia: Lack of normal, coordinated cell differentiation. Metastasis: Cancer cells develop the capacity for discontinuous growth and dissemination to other parts of the body. Clonality: Cancer originates from genetic changes in a single cell which proliferates to form a clone of malignant cells. Autonomy: Growth is not properly regulated by the normal biochemical and physical influences in the environment.
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Oncogenes Genes which cause malignant transformation when inappropriately expressed because of mutation, amplification or rearrangements. Suppressor genes They act by inhibiting cell growth, and a related category of genes can act by inducing programmed cell death.

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Classification of oral cancer

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International Classification of Disease for Oncology

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NATIONAL CANCER REGISTRY PROGRAMME AN OVERVIEW

The Indian Council of Medical Research initiated a network of cancer registries across the country under the National Cancer Registry Programme (NCRP) in December 1981. The programme was commenced with the following objectives: 1. To generate reliable data on the magnitude and patterns of cancer. 2. To undertake epidemiologic studies in the form of case control or cohort studies based on observations of registry data

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3. Provide research base for developing appropriate strategies to aid in National Cancer Control Programme; this would be in the form of planning, monitoring and evaluation of activities under this programme;

4. Develop human resource in cancer registration and epidemiology.

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Data collection commenced from 1 January 1982 in the population based cancer registries (PBCRs) at Bangalore, Chennai and Mumbai, and also in the hospital based cancer registries (HBCRs) at Chandigarh, Dibrugarh and Thiruvananthapuram. From 1986 two more urban population based cancer registries were started in Delhi and Bhopal. For the first time a population based rural cancer registry was also started by the ICMR during the subsequent year (1987) in Barshi in the state of Maharashtra. In order to extend the assessment of cancer patient care, hospital based cancer registries were also started at Bangalore, Chennai and Mumbai in 1984.

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Cancer registries collect information on cancers reported in a prescribed format with specified guidelines and the data so collected is entered on a computer. All registries are required to register all malignant neoplasm's coded as per the International Classification of Diseases for Oncology (ICD-O) with a behavior code.
Of the ten million new cases of cancer diagnosed every year over half are from the developing world. It is estimated that by the year 2020, over 10 million people worldwide would die of cancer every year and that 70 percent of these would be from the developing world.

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Cancer incidence refers to the number of new cases of cancer seen in the population of a defined geographic area over a definite period of time. Site-specific annual cancer incidence rates are the number of site-specific cancers in a year per 100,000 persons at risk

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Cancer Incidence - All sites (ICD-9: 140-208)

Registry Bangalore Barshi Bhopal Chennai Delhi Mumbai All Registries Males 10240 638 2539 11366 26218 28953 79954 Females 11740 766 2250 12355 25861 27091 80063 Total Cases 21980 1404 4789 23721 52079 56044 160017

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Cancers of Sites associated with use of Tobacco Sites of cancer that have been associated with use of tobacco (Tobacco Related Cancers . TRCs) include oral cavity, pharynx (including oropharynx & hypopharynx), oesophagus, larynx, lung and urinary bladder. In males this proportion varies from 35.6% in Bangalore to 50% in Bhopal, whereas in females Bangalore has the highest proportion of 17.3%.

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Proportion (%) of Tobacco Related Cancers relative to all sites

Males Females

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SUMMARY OF SELECTED INDIVIDUAL SITES

The following pages provide a summary of some statistical and scientific details on individual sites of cancer. The sites are as per the International Classification of Diseases (ICD9) and not grouped by system, mainly because of easy comparability of data with registries across the world.

The details provided, pertains to the actual number (No.) of cancers seen in the six registries in the seven year period (1990-1996) and their proportion or percent (%) relative to all sites of cancer for that gender.

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It includes the order or rank (R) of the site of cancer, among all sites of cancer in that gender and is based on the crude rate. The Age Adjusted Rate (AAR) per 100,000 population is also provided. Wherever, applicable the male: female ratio based on actual numbers in each sex is given

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Tongue: males

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Oral cavity : males

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Oral cavity: female

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Types of Oral Cancer

Lip: carcinoma of lip most commonly occurs in elderly men. Lower lip is commonly involved than upper lip.

Tongue: constitutes 2550% of all intraoral cancers. More common among men
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Gingiva: constitutes an important group of neoplasms as diagnosis is always delayed. Chronic irritation has been speculated as the cause
Floor of mouth: constitutes 15% of all intraoral cancers. Pipe or cigar smoking is considered as etiologic factor.

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Cancer of buccal mucosa and labial mucosa, more common in men.

Mostly seen in habitual betel quid chewers.

Carcinoma of labial mucosa

Cancer of palate constitutes for 9% of incidence.

Commonly seen with reverse smoking

Carcinoma of the palate

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Clinical presentations of cancer of oral mucosa

More than 90% of oral cancers are squamous cell carcinomas. The other 10% are salivary gland tumours, lymphoma, sarcoma and others. Many oral lesions are ill-defined, variably appearing, controversial and poorly understood lesions that fortunately are benign, but may present changes that can easily be confused with malignancy. Conversely, an early malignancy may quite often be mistaken for a benign lesion.

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Some lesions considered premalignant because they are statistically correlated with subsequent associated cancerous changes. A considerable amount of clinical uncertainty is involved in the early detection of malignancy as well as in the understanding that many of these lesions may not always remain benign. However, following clinical signs should be regarded with great suspicion.

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Ulcer: Any ulcer of the mucosa, which fails to heal within two weeks, with appropriate therapy and for which no other diagnosis, for example, major aphthous ulcer, can be established. Induration of any mucosal lesion. Fungation/growth of the tissues to produce elevated, cauliflower surface or lump.

Fixation of the mucosa to underlying tissues, with loss of normal mobility.

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Failure to heal of a tooth socket or any other wound.

Tooth mobility with no apparent cause.

Pain/paraesthesia with no apparent cause. Dysphagia for which no other diagnosis can be made. White/red patches of the mucosa are commonly considered as potentially malignant lesions, but occasionally they may be the clinical presentation of a malignancy.

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Lymphadenopathy: The lymph nodes of the head and neck should always be palpated as part of clinical examination by every dentist. Enlargement of one or more nodes may be a response to infection of an ulcerated tumour, but may indicate metastasis, especially if multiple, hard, matted together or fixed to skin or deeper structures. The precise group of nodes likely to be affected depends on the location of the primary cancer, but submandibular, then upper, middle and lower deep cervical nodes are most commonly involved with intraoral cancerous lesions. The more node groups involved and the lower the level in the neck, the more serious is the prognosis for the patient, as this indicates more extensive spread.
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Global scenario of oral cancer

Cancer is one of the major threats to public health in the developed world and increasingly in the developing world. In developed countries, cancer is the second most common cause of death.
According to the World Health Report 2004, cancer accounted for 7.1 million deaths in 2003, and it is estimated, the overall number of new cases will rise by 50% in the next 20 years.

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Cancer pattern (WHO)

Type 1. 2. 3. 4. 5. 6. Lung Breast Stomach Cervix Oral Liver Developed Countries 50% 23% 21% 4.3% 2.6% 1.1% Developing countries 4.1% 8% 19.9% 29% 25% 2.1%

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Oral cancer is a serious and growing problem in many parts of the globe. Oral and pharyngeal cancer, grouped together, is the sixth most common cancer in the world. The annual estimated incidence is around 275,000 for oral and 130,300 for pharyngeal cancers excluding nasopharynx, two-thirds of these cases occurring in developing countries.

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There is a wide geographical variation (approximately 20-fold) in the incidence of this cancer. The areas characterised by high incidence rates for oral cancer (excluding lip) are found in the South and Southeast Asia (e.g. Sri Lanka, India, Pakistan and Taiwan), parts of Western (e.g. France) and Eastern Europe (e.g. Hungary, Slovakia and Slovenia), parts of Latin America and the Caribbean (e.g. Brazil, Uruguay and Puerto Rico) and in Pacific regions (e.g. Papua New Guinea and Melanesia).

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In high-risk countries such as Sri Lanka, India, Pakistan and Bangladesh, oral cancer is the most common cancer in men, and may contribute up to 25% of all new cases of cancer.

On a visit to a cancer treatment centre in any of these high-risk countries in south Asia, one may find that at least up to a quarter of the patients warded are suffering from oral cancer.

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Indian Scenario
India has one of the highest incidence of oral cancers in the world. Oral cancer is the leading type of cancer in India (constituting 60% of all the cancers). Incidence varies between regions within a country. The high incidence of oral cancer and oral pre-cancerous lesions in India has long been linked with the habit of betel quid chewing incorporating tobacco.

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Oral cancer ranks number one among men and number three among women in India. Oral cancer constitutes 12% of all cancers in men and 8% of all cancers among women. As high as 16.7 per 1 lakh males have been reported from Bombay and 17.2 per lakh females reported from Bangalore.
Most affected site is tongue in Bhopal and buccal mucosa in Chennai.

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It is estimated that there are about one and half million cases of cancer in the country at any given time with about half a million new cases being added every year. Out of these 1/3rd of the cases are that of oral cancer, which amounts to 5 lakh cases of oral cancer at any given time. Such a high incidence in the Indian population merits indepth probing of various aetiological and contributory factors so that effective preventive measures could be identified and instituted.
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WHO Data for INDIA

1. Oropharyngeal Cancer 2. Cervical Cancer 3. Breast Cancer 34.9% 26.6% 7.4%

4. Lung Cancer

4.0%

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Incidence and mortality rates (age standardised) by cancer type in India(sexes combined) data extracted from Globocan, 2008 data.

Source: Ken Russell Coelho . Challenges of the Oral Cancer Burden in India. Journal of Cancer Epidemiology, Volume 2012,
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Source: Ken Russell Coelho . Challenges of the Oral Cancer Burden in India. Journal 74 of Cancer Epidemiology, Volume 2012,

Source: Ramnath Takiar*, Deenu Nadayil, A Nandakumar. Projections of Number of Cancer Cases in75 India (2010-2020) by Cancer Groups. Asian Pacific Journal of Cancer Prevention, Vol 11, 2010

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The estimated new cases of cancer in India per year is nearly 6.5 lakhs and at the start of the next millenniums estimated to be 8,06,000. The crude incidence of cancer in India is approximately 100 per 100,000 population.

This is only a third or fourth of the incidence in the affluent countries of Europe and North America. The Cancer in women in the Indian Sub-continent constitutes more than 50% of the total cancer. The most common cancer observed by Indian registries are those related to tobacco usage in males while among females, the most common cancer are those of the Uterine Cervix, Breast and Oral cavity.
http://kidwai.kar.nic.in/general.htm
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In Karnataka a state in the southern part of India, it is estimated that annually there are about 35,000 incident cancers whereas, the prevalent cancer accounts to about 1,50,000. More than one third of these cancers are seen and attended to at Kidwai Memorial Institute of Oncology. Most of these cancers, especially in women are easily accessible and have sensitive early detection tests and techniques. In addition, Cervix and oral cancers have well established phases of evolution from pre cancer to cancer. Thus are ideally suited for both primary and secondary prevention.

http://kidwai.kar.nic.in/general.htm

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EPIDEMIOLOGICAL TRIAD
AGENT

ENVIRON MENT

HOST

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1. Host factors
Age Sex Ethnic basis Site distribution Trends Genetic Susceptibility Heredity Blood groups Socio-economic Status Occupation Custom/habits Culture
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Age Distribution
The incidence of oral cancer increases with age, although the pattern differs markedly in different countries and with different risk factors. In the west, 98% of cases are in patients over 40 years of age, whilst in the high prevalence areas like south-east Asia including India, parts of South America (e.g. Brazil), the western pacific, France and eastern Europe, many cases occur prior to the age of 35 years due to heavy abuse of various forms of smokeless tobacco.

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The observation that oral cancer generally occurs with advancing age indicates that over the time certain sequenced alterations in the biochemical/ biophysical processes (nuclear, enzymatic, metabolic, immunologic) of aging cells with a particular genetic predisposition undergo and accumulate mutations, resulting in carcinogenic transformation.

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Approximately 96% of oral cancer is diagnosed in persons older than 40 years and more than 50% of all cancers occur in persons over the age of 65 years. The average age at the time of diagnosis is 63 years. Recently however, evidence has emerged indicating that oral cancers are occurring more frequently in younger persons (less than 40 years).

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Source: R Kalyani, Subhashish Das, ML Harendra Kumar Pattern of Cancer in Adolescent and

Young Adults A Ten Year Study in India. Asian Pacific J Cancer Prev, 11, 655-659

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Sex distribution
In industrialized countries men are affected almost twice as often as women, probably due to their higher indulgence in risk factors such as alcohol and tobacco consumption, for intraoral cancer and sunlight for lip cancer.

The incidence of cancer of buccal mucosa, gingiva and other parts of oral mucosa for women is, however, greater than or equal to that for men in high prevalence areas such as India, where chewing and smoking are also common among women.

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Men and women are also almost equally affected in some of the ethnic groups in Singapore, Denmark and Hawaii. The ratio of males to females diagnosed with oral cancer is 2 : 1 over lifetime although the ratio comes closer to 1 : 1 with advancing age.

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Data obtained from American Cancer Society in a study period of 25 years (1978-2003)
Type Lung cancer Prostate cancer Bladder Gastric Cancer Leukemia Oral Cancer Percentage in Males 22% 16% 14% 4% 3% 3%

Data obtained from American Cancer Society in a study period of 25 years (1978-2003)
Type Breast cancer Lung Endometrium Cervix Oral Cancer Percentage in Females 26% 15% 9% 4% 3%

On the Global Basis (Ranking)

Males Lung Stomatch Colo-rectal Oral Prostate Oesophageal Female Breast Cervix Stomatch Colo-rectal Lung Oral Both sexes Stomach Lung Breast Colo-rectal Cervix Oral

Site and Sex-wise distribution of Oral Cancer

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Source: R Kalyani, Subhashish Das, ML Harendra Kumar Pattern of Cancer in Adolescent and

Young Adults A Ten Year Study in India. Asian Pacific J Cancer Prev, 11, 655-659

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Registries, 1964- through the initiation of National Cancer

Registry Program(NCRP) establiched by ICMR.

Males per 1 lakhs Registry

16.7 Bombay

Females per 1 lakhs

9

14.9
13

Poona
Madras

9.4
12.6

10.2

Bangalore

17.2

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Based on currently available data, males in Bhopal have the highest age adjusted incidence rates of cancer of the tongue (8.8 per 1 lakh) followed by Delhi(6 per lakh)and Mumbai (5.7 per lakh).

Similarly the rates of cancer of the oral cavity in both males and females in all urban registries are among the highest in the world.

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Ethnic Basis
Ethnicity strongly influences prevalence due to social and cultural practices. Where such habits represent risk factors, there continuation by emigrants from high prevalence regions to other parts of the world results in relatively high cancer incidence in immigrant communities. Other studies show that black Americans, for example, experience significantly more pharyngeal cancers than their white counterparts.

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Site Distribution
Lip cancer is most common in fair skinned races, particularly in rural areas and in men who work out of doors. Intraoral cancer in western countries most commonly affects the lateral borders of the tongue and the floor of the mouth, followed by the buccal mucosa, mandibular alveolus, retromolar region and soft palate. Comparatively hard palate and dorsum of the tongue are the lowest risk sites. In the high-risk areas of south Asia, the buccal, retromolar and commissural mucosa are the most prone sites.

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3% 3%

4% 3%

Buccal mucosa Ant 2/3rd tongue Lower gum upper gum Floor of mouth
50%

13%

24%

Lip Hard palate

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Trends
In urban parts of high incidence regions, e.g. in Mumbai, there may be a fall in oral cancer which could be attributed to change from pan (betel) chewing and bidi smoking to the smoking of manufactured cigarettes.

The rising trend of tongue cancer in young men in western countries is thought to be due to marked increase in alcohol consumption, perhaps combined with increased use of smokeless tobacco products, especially in the USA and Nordic countries.

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According to 15-year prospective study carried out by Sunny et al in males, a statistically significant decreasing trend in the overall age-adjusted incidence rates were observed during the period 1986 to 2000, with an yearly decrease of 1.70%.

This decrease was significant for men above the age of 40, but for young adult men below the age of 40, there was no significant decrease, the level being stable. In females, the overall decreasing trend in the age-adjusted incidence rates of oral cancers was not significant, but in the age group of 4059, a significant decline was observed.
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Genetic Susceptibility
Because of their genetic make up certain people are at higher risk for cancer. There are 3 types of genetic factors in cancer Chromosomal with genetic imbalance-entire genetic material is absent or in excess Single gene locus - mutation either in allele as a dominant trait or in paired alleles as a recessive trait Polygenic -Too many genes interact With environmental factors ,with no one gene or factor playing a major role

Heredity
Recent family studies have shown that first degree relatives of patients with oral cancer may have up to 3 or 4 times the risk of developing an oral cancer themselvesperhaps as much as 15 times the risk of getting a cancer somewhere in the upper aerodigestive tract of lungs. Such effects may result largely from shared environment including passive smoking but also point to a small effect of genetic predisposition.

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Blood groups
Association of blood groups with oral cancer has also been observed. It has been reported that Group O showed the least susceptibility, Group B and AB showed doubtful susceptibility and Blood Group A showed higher susceptibility. (Jaleel BF,2012)

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Socio-economic status
Oral cancer are common in lower socio economic status as compared to higher socioeconomic people May be attributed to the lower nutrition status of this population.

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Occupation
Certain occupation where exposure to carcinogens are common like manufacturing tar, certain oils, textile industries, water works rubber workers etc. But its implication in oral cancer is rare however a study is reported by Hyat showed high incidence of oral cancer among male textile workers in England and Whales in 1972.

Custom / Habits:
Less in 7th day Adventist Christians than other Christian population because of the strict prohibition of smoking and alcohol by the church.

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Culture:
Certain cultural pattern encourage smoking and alcoholism like in tribal people (Navago Indians, Red Indians)

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2. Agent factors
Etiology and Risk factors for Oral Cancer

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1. PHYSICAL AGENTS : Ultraviolet Radiation Ionizing Radiation Continuing G Heat Due to severe chutta smoking Solar radiation Sunlight.
2. CHEMICAL AGENTS: Benzopyrene and its derivatives Nitrosamines thiamine nitrous amines. Polycyclic aromatic hydrocarbons Aromatic amines Azodyes Alpha toxin Hormones: Estrogens and androgens Others Nicotine & Rmenacetin .
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3. NUTRITIONAL AGENTS: Deficiency of proteins, vitamins and certain minerals Alcohol Food Contaminants. 4. MECHANICAL FACTORS Chronic Irritation / Friction / Trauma results in Cancerous Changes. ill fitting of dentures Over hanging fillings Sharp tooth cusp Broken teeth, ragged teeth etc.
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BIOLOGICAL AGENTS: Hepatitis B Virus: Patients with hepatitis are more prone patient to develop hepatic carcinoma in future Epstein Barr Virus ( E-B Virus): It is the causative agent for Burketts lymphoma, which may develop in the oral cavity. - Human Papilloma Virus (HPV)

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The etiology of oral cancer is almost certainly multi-factorial and involves many alterations in host immunity and metabolism, angiogenesis and exposure to chronic inflammation in a genetically susceptible individual.
The carcinogenic changes may be influenced by oncogenes, viruses, irradiation, drugs, tobacco, alcohol, hormones, nutrients and physical irritants.

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There is an excellent evidence from many sources around the world that use of tobacco is by far the most important risk factor for oral cancer. Prevalence of tobacco use has declined in some high income countries, but continues to increase in low and middle income countries, especially among young people and women. According to WHO (1984) in developing countries like India, chewing of tobacco, often in association with areca nut in the form of betel quid or pan is the most important cause of oral cancer.

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Tobacco
Tobacco can be broadly classified into 2 forms Smokeless form -- paan, mainpuri tobacco, mawa, mishri, masheri, zarda, gurakhu, gutkha, snuff Smoking form -- manufactured cigarettes, bidis, cigars, pipes, kreteks, sticks

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History of tobacco
Christopher Columbus set sail in 1492.

When the Portuguese eventually did land on India's shores, they brought in tobacco.
The taste for tobacco, first acquired by the Indian royals, soon spread to the commoners and, in the 17th century, tobacco began to take firm roots in India. In 17th century the British East India Company began growing tobacco in India as a cash crop. In the late 19th century, the beedi industry began to grow in India.

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Tobacco components

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Smokeless forms of tobacco

The use of smokeless tobacco is an important cause of oral cancer, particularly in India and its evidence is largely derived from case control studies.

The reported risks of developing oral cancer in chewers are

2-4 times higher as compared to those with no tobacco habits.

(Jussawall and Deshpande 1971, Notani and Sankaranarayanan et al ,Nandakumar et al 1990)

Jayant

1987,
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Smokeless tobacco, whether of the chewing variety or snuff, masheri or nass contain several carcinogens of which tobacco specific nitrosamines are the most significant.

Brunnemann and Hoffman 1992, Bhide et al 1989.

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PAAN

Most common form dating back to more than 2000 years. Paan refers to betel leaf (from piper betel wine). Quid (also called beeda, tambula) contains areca nut which may be used raw, baked or boiled lime obtained from lime stone or sea shells, and according to local customs may include aniseed, catechu, cardamom, cinnamon, coconut, cloves, sugar and tobacco.

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MAINPURI TOBACCO
Includes tobacco, slaked lime, finely cut areca nut, camphor and cloves. All this made into a paste and smeared on betel leaf and chewed. Mainpuri name comes from a place in U.P near Agra, where it is usually chewed and famous among locals. A high prevalence of oral leukoplakia and oral cancer has been found in this place and among these people who regularly chew mainpuri paan.

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MAWA
Preparation of thin shavings of areca nut with addition of slaked lime and tobacco. Commercially available in small ball form packed in a pouch. Before consumption the pouch is vigorously rubbed in palm to mix the contents. Consumed in Gujarat, Bihar and eastern India.

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MISHRI
Prepared by roasting tobacco on a hot metal plate until it is uniformly black.
It is then powdered and used with catechu. Catechu is an residual extract obtained from soaking bark of a hard wood tree ACACIA CATECHU in boiling water. Used in Maharashtra especially by women.

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ZARDA
Tobacco leaf boiled in water along with lime and spices until evaporation. The residual tobacco is then dried and coloured with dyes.

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GURAKHU
Tobacco Paste powdered and mixed other ingredients. with molasses and

Used as a tooth paste in Some parts of India especially Bihar.

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GUTKHA
It is prepared by crushing betel nut, tobacco and adding some sweet or savory flavor.

Gutkha has originated in India ,but because of its sweet flavor it is taken up by western countries and widely used.

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SNUFF
Dry snuff is a finely powdered tobacco that is inhaled through the nose or taken by mouth. Once widely used now has declined. Moist snuff is a powdered tobacco finely ground, held between cheek and gums. Other parts of moist snuff includes khaini, shammah and Naas or naswa.

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KHAINI PAN MASALA

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CREAMY SNUFF:
It is a tobacco marketed in tooth paste like tubes. This tobacco habit is popular among children in Goa. Recently, the manufacturers of this product has been banned by the government.

PATTIWALA TOBACCO: sun-cured tobacco leaf used with or

without lime.

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KIWAM:

tobacco leaf boiled in water with rose water and spices (e.g., saffron, cardamom, musk) used as a thick paste or it further dried, as granules or pills.

RED TOOTH POWDER (LAL DANT MANJAN):

It is a commercially available dentifrice that contains a significant proportion of tobacco.

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Betel nut alone can be carcinogenic and appears to be responsible for high incidence of oral cancer in Melanesia where it is often taken along with smoking. Betel nut contains Tannins which acts as a constant irritant, precipitating proteins and hence damage mucosa. Phenols in betel nut can cause burning sensation and Arecoline {alkaloid} can stimulate fibroblast proliferation and collagen synthesis. Betel nut is the major cause of distressing condition. Oral sub mucous fibrosis, which has a high rate of malignant transformation. The risk of tobacco consumption increases with the amount of tobacco consumed per day and the number of years consumed.

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Soaking and boiling betel nuts in water reduces Alkaloids and Tannins. But Arecoline has powerful parasympathetic properties like producing euphoria and counteracting fatigue. Before marketing the areca nut in India, the manufacturers dip the boiled areca nuts in the fermented liquor obtained from previous year boiling of areca nuts to incorporate this euphoriant effect into the nuts for better market value and promote increased consumption.

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The case against tobacco is further strengthened by the findings that oral cancer almost always occur on the sides of the mouth where the tobacco quid was kept, and probability of developing cancer is directly related with the duration and intensity of use.

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Contents of smokeless tobacco

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Smokeless forms of tobacco

Smoking form of tobacco

Bidis Cigarettes Chillum Chutta/cheroor Dhumti Hookah Hookli Ghudhaku

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BIDIS
Bidis consists of small amount of tobacco hand wrapped in dried temburni leaf and tied with strings. Bidis are widely used throughout south east Asia and mainly in India. 34% of total production 0.2-0.3 gm Sun dried tobacco flakes hand rolled in temburni / tendu leaf & tied in thread. nicotine content of 1.7 to 3mg. Tar content 45-50mg

142

CIGARETTES
Cigarettes consist of shredded or reconstituted tobacco processed with hundreds of chemicals. They are the predominant form of tobacco used worldwide. sugars, flavoring and aromatic ingredients 1-1.4mg of nicotine and 19-27mg tar 1 gram of tobacco cured in the sun or artificial heat is covered with paper.

31% of tobacco grown in India is used for manufacture of cigarettes

143

CHILLUM
10-14cm.,long conical clay pipe Chillum is held vertically to prevent tobacco from entering mouth.

Filled with coarsely cut tobacco pieces and a glowing

charcoal is kept on top of tobacco.

144

CHUTTA/CHEROOR
Small cigars made of heavily bodied tobacco Cylindrical Air cured and fermented tobaccos with a tobacco wrappers

Most wide spread in A.P, Tamil Nadu.

145

DHUMTI
Somewhat conical cheroots Occasionally for reverse smoking. Rolled leaf tobacco is used inside a leaf of jack fruit tree. Sometimes dried leaf of banana is used.

146

HOOKAH
Also called water-pipe or hubble-bubble. Mughal culture Purely of Indian origin, which corresponds with introduction of tobacco in INDIA

147

HOOKLI
Short clay pipe 7-10 cm. with a mouth-piece and bowl. Tobacco is placed in the bowl, and the smoke is inhaled through the stem. GUJARAT

148

GUDHAKHU
A traditional mix.
Used to clean teeth. Predominantly used by women in BIHAR

149

These are clove-flavoured cigarettes. They are widely smoked in Indonesia.

KRETEKS: STICKS:

These are made from sun-cured tobacco known as brus and wrapped in cigarette paper

150

Reverse Smoking
Common in India

In the coastal areas of Andhra Pradesh especially Visakhapatnam and Srikakulam districts and in parts of Orissa, chutta (Pikka) is smoked in this fashion.
The temperature of the palatal mucosa may go up to 580c. Not to expose lighted end to wind and water, prevent husband from seeing it, prevent ashes from falling on child, toothache and halitosis relief.

151

The relationship between reverse smoking with the burning end inside the mouth, and palatal cancer is well established in India by Reddy et al 1982. In western countries the effect of cigarette smoking has usually been studied along with alcohol drinking with respect to cancer of the oral cavity and pharynx.
Rothman and Keller 1972, Blot et al 1988, Tuyns et al 1988, Franceschi et al 1990, La Blot et al

152

The risk ratio associated with cigarette smoking and non drinkers of alcohol, for cancers of the mouth and pharynx have been reported from a low of 1.5 fold to a high of almost 12.9 fold and a dose response relationship has also been demonstrated. While the risk of those who smoke and drink alcohol goes up to 100 fold depending on the frequency of smoking and the amount of alcohol consumed per day.

153

Pipe and cigar smokers have also been reported to be at a higher risk for oral cancer as compared to non smoker. Pipe smoker are particularly at a higher risk for cancer of the lip. Keller 1970.

It has been demonstrated that the risk of oral/ pharyngeal cancers associated with cigarette smoking decreases sharply with cessation of the habit and reaches the risk of level of non smokers after ten years of quitting. Blot et al

1988

154

Attributable risk
For the Indian population the proportion attributable to tobacco use both smoking and chewing has been estimated to vary form 61 percent to 70 % (81% for males and 36% for females) for oral cancer. Notani and Jayant et al 1977.

155

Risk Ratios for Oral Cancer at Various Subsites

Site Betel-tobacco quid Bidi Smoking Betel-tobacco quid chewing and bidi smoking

Oral cavity

4 - 7.6

2- 2.8

4 - 11.9

Subsites
Buccal mucosa, lip and gingiva Anterior tongue Palate Gingiva Base of tongue and oropharynx Tongue and floor of the mouth 11.6 3.3 16.9

3.4 1.3 4.1 13.2 3.3 6.1

1.9 1.2 2.1 2.6 11.8 5

7 2 16.3 31.7 7
156

Alcohol
There has been consistent strong evidence that alcoholic beverages increase the risk of oral/pharyngeal cancer and that alcohol acts synergistically with cigarette smoking. WHO has found an association between liver cirrhosis and cancer of tongue. The reported risk for Alcohol consumers vary from 2 - 100 fold depending on amount consumed, type of alcohol, whether or not accompanied by cigarette smoking and the sub site considered in the oral / pharyngeal region.
157

In India alcohol drinking does not emerge as a strong risk factor, as the risks reported for alcohol consumers were relatively much lower than those for tobacco smokers and chewers. Notani

Sankarnarayanan et al.

It has been suggested that the mechanism of alcohol cancer association may be related to nutritional deficiency, which could increase susceptibility to the carcinogenic potential of an external agent like tobacco.

It may also act as a solvent and enhance penetration of carcinogens into target tissues or the effect may be attributed to contamination of the product.
158

In a study, Harty have reported that ADH3 genotype affects the rate of metabolism of alcohol to acetaldehyde. Heavy drinkers homozygous for allele ADH3 are faster metabolizers and consequently are at a higher risk for developing oral cancer as compared to heavy drinkers with other ADH3 genotypes.

159

Role of Tobacco and Alcoholic Beverages in the aetiology of Cancer of the Oral Cavity

122 cases and 606 controls were compared with respect to lifelong alcohol and tobacco consumption. 4 to 6 fold increase in risk among subjects with medium or high tobacco consumption was observed. An effect of alcoholic beverages was found in subjects with an average daily consumption of 120 ml of alcohol, with a higher risk

in beer drinkers.

Franco Merletti et al ,Cancer Res September 1, 1989 49;4919

160

Dietary Factors
The importance of diet and nutrition in the etiology of human cancer has gained wide acceptance. The observation that migrant populations experience the cancer rate of the host country, the evidence that international differences in the rates were the result of the environmental and lifestyle factors including among other possibilities dietary and nutritional factors.

161

There are internal and external factors which modify the risk for developing cancer and diet is one such factor. There are various ecologic and case control studies but information gathered by ecologic studies is of limited validity because of the lack of data necessary to control for the confounding effects of the important risk factors of tobacco smoking and chewing, while on one can control those in case control studies.

162

Several major case control studies have been reported from the western countries. One of the largest case control study was reported from the US on 871 cases and 979 control, frequency matched for age and sex.- McLaughlin et al 1988.

Meat, fish, grains and dairy products showed no association with the risk in females, where as in males, meat and dairy products increased and fish decreased the risk.

163

However fruits in general including citrus fruits and dark yellow fruits decreased the risk in both the sexes. Marshall et al reported that low intake of vitamins C and A was associated with doubling of the risk. Lavecchia et al of the sixteen food items studied eggs, cold meat, fish , bread / pasta, butter , margarine and oil showed no association, however a protective effect was seen with cheese, carrots, green vegetables and fresh fruits, milk and meat.
164

A single case control study exploring the association of individual food items has been reported from India region of high incidence of oral pharyngeal cancer Notani and Jayant, this study was based on cancers in males at a large referral hospital, and compared the diet of cancer cases with two groups of controls, hospital and community.

165

The findings were reported for the usual diet before the onset of the disease in terms of frequency of intake, after adjusting for tobacco use. A protective effect was observed with an intake of vegetables, fish, pulses and buttermilk.

The use of red chili powder emerged as a risk factor. The consumption of fruits was poor in both cases and controls and its role could not be evaluated.

166

An exhaustive review of epidemiological evidence on the relationship between nutrition and oral cancer published by Marshall and Boyle 1996 discussed the limitations of dietary case control studies.

On the basis of exploratory studies conducted by TATA MEMORIAL HOSPITAL, MUMBAI regarding the role of diet on oral cancer, it was reported that those who do not eat vegetables daily, or consume fish, butter milk, pulses and fruits had and higher chance of developing oral cancer. It was also observed that non vegetarians had a higher incidence of oral cancer than vegetarians.
167

Vitamin Deficiencies Cancers of the mouth have been related to low intake of fruits and vegetables indoles , flavonoids, isothiocyanates, terpenes and phenolic antioxidants. Inverse relationship between ingestion of carotenoids and oral cancer was seen. vitamin A deficiencies causes hyperkeratosis which in turn shows high rates of cancer.

168

Iron deficiencies Plummer-vinson syndrome, which has been associated with an increased risk of developing carcinoma of the tongue

169

Viruses
Saranath has reported that Oral cancer :25-50% prevalence of EBV Premalignant lesions 0-13% Normal mucosa : 4 - 28%. HPV-16 and HPV-18 was detected in higher proportion of oral lesions compared to oral cancer cases probably implying its importance in early events of carcinogenesis. Dcosta et al, Saranath.1999 Herpes simplex virus type I, EBV, HHV-6, 8 and HIV are all associated.
170

Syphilis
patients with oral cancer have indicated positive histories and serological tests indicating the presence of syphilis

171

Dentures
People with poor dental health such as sharp, broken teeth, dental sepsis or trauma from ill-fitting dentures are at slightly increased risk for developing oral cancer. However, these are often patients with poor diet, poor selfimage, and folk who lead generally unhealthy lifestyles. Sorting out the really important causes of cancer in these individuals may be difficult.

172

Potentially malignant lesions or conditions

1. Leukoplakia
A raised white patch of oral mucosa measuring 5mm or more which cannot be scraped off and which cannot be attributed to other diagnosable disease.

Homogenous
Ulcerated

Nodular
174

Rates of malignant transformation of leukoplakia have been estimated at 2.2% to 6%- (1993) 40% of cases regress. However when a lesion develops cracks, bleedings or area of redness and erosion and candidal infection, an increased risk of malignant transformation is seen.

www.oralcancerfoundation.org/dental/pdf/canadian_study
175

WHO colloborating reference centre for oral pre cancerous lesions reports that the most common sites for Leukoplakia to occur are usually habit dependant and site specific. Silverman has reported that leukoplakia in non smokers referred to sometimes as idiopathic leukoplakia exhibit a higher rate of malignant transformation than in smokers 16%. According to previous studies conducted world wide including Indian studies reports that the most common sites for occurrence of Leukoplakia are .. Buccal mucosa 31% Tongue 24% Retro molar region 22%
176

2. Erythroplakia
It is a bright red, velvety plaque which cannot be characterized clinically or pathologically as any other lesion. Prevalence: About 0.02% : India

95% malignant potential

177

3. Oral submucous fibrosis:

Is a chronic mucosal condition affecting any part of the oral mucosa, characterized by mucosal rigidity of varying intensity due to fibroblastic transformation of the juxtaepithelial connective tissue layer. The presence of palpable fibrous bands is a diagnostic criterion for submucous fibrosis.
An increase in OSMF has been observed in the cashew workers in kerala. It is believed that the cashew shells when removed before roasting liberate irritant shell oil. This oil when inhaled repeatedly becomes a predisposing factor for OSMF. OSMF has been observed more in the individuals with blood group A.
178

Ramanathan 1981 reported OSMF as a mucosal change secondary to chronic iron and vitamin B complex deficiency. This theory is supported by the occurrence of OSMF in Indians staying abroad but maintaining Indian dietary habits like use of spices and chilies. PAYMASTER in 1956 reported that the malignant transformation of OSMF is as high as 17.6% after a follow up period of 7 years in a study conducted among tobacco chewers in Ernakulam, kerala.
179

4. Lichen planus
Approximately 0.2 per cent of OLP patients develop oral SCC each year. frequently in atrophic, erosive and plaque lesions.

180

Use of mouth wash and oral cancer

As long as 1979 concern was expressed about the possibility of high alcohol containing mouthwashes contributing to oral cancer, when 10 of 11 non smoking, non drinking patients with oral cancer were found.

Risk generally increased in proportion to frequency and duration of mouthwash use and were only apparent when alcohol content of the mouth wash exceeded 25%. The effects were stronger in women than men.
However the most recent study by Winn et al showed no increased risk of oral cancer associated with the use of mouthwashes containing >25% ethanol.
181

Sunlight
Prolonged exposure to ultraviolet radiation from the sun can cause skin cancer. People who are outdoors for an extended period of time increase their risk of lip cancer, as well. More than 30 percent of lip cancer diagnoses are in persons with outdoor occupations.

182

3. Environmental factors
Air pollution has resulted in inclusion of certain harmful chemical substances into the atmosphere e.g., ACRY Lonitrite ALKYC Sulphates Aromatic Amines etc.

Occupations like- farming, fishing, forestry etc are at risk due to prolong exposure.

Countries near tropics and equator where air is cleaner and UV rays are not trapped cancers can account for about 60% of all oral cancers.
183

Diagnosis of oral cancer

At present in developing countries , more than 50 % of oral cancers are detected only after they have reached an advanced stage. By this stage, the cancers are disfiguring and painful, the treatment is both extensive and expensive and survival rates are low with less than 1/10th of patients surviving even 5 years.

The majority of these cancers and these lesions can be detected for upto 15 years prior to their change to invasive cancer.

184

In addition to complete medical history and physical examination, diagnostics procedures for oral cancer may include the following Biopsy Exfoliative cytology Toluidine blue staining Computed tomography scan Ultrasound Magnetic resonance imaging
185

Brush biopsy of oral cancer

It is a procedure in which tissue samples are removed (with a needle or during surgery) from the body for examination under a microscope to determine if cancer or other abnormal cells are present.

The Oral CDx oral brush biopsy is a reliable non-invasive and simple chair side procedure to determine if an oral lesion is benign or potentially harmful. Pre-cancerous and early stage oral cancerous lesions can be determined.

It is essential that these early stage malignancies be checked to improve diagnosis. The painless procedure can be done without local anesthetic.

187

The oral biopsy brush is pressed against the lesion and rotated 510x or more depending on the thickness of the lesion. The cellular material collected on the brush is then transferred onto a glass slide. All brush biopsy specimens are sent to Laboratories for computer image analysis, assisted identification and display of any abnormal cells. If a positive report is obtained it will be necessary to obtain a histological section to grade the abnormality once it is identified in order to completely characterize the lesion histologically. Biopsy specimens can also be obtained from tissue samples removed from a needle, blades during surgery.
188

The slides are scanned by the Oral CDx computer system and the Images of abnormal cells are identified by the computer system and are individually displayed on a highresolution color video monitor for final review by a expert pathologist. The specimens are then categorized into whether they are negative/atypical/positive/inadequate.

There are chances of high False Positive Rate.

189

Exfoliative cytology
This is a histological examination of surface cells scrapped from a suspected lesion with a tongue blade. The accuracy of this procedure is highly variable, and the procedure is especially weak in detecting pre malignant lesions.

Both false positive and false negative readings are common. The variety of clinical and histological appearances found in oral cancer, casts a doubt on the validity of diagnoses made from microscopic examination of surface cells alone. Exfoliative cytology is ineffective with lesions that have a heavy keratin layer or in lesions where abnormal cells are below the surface layer.

191

Even though, this technique is positive for malignancy it has to be substantiated with tissue biopsy. The smear obtained from exfoliative cytology is subjected to cytological analysis and interpreted as follows. CLASS 1 Normal CLASS 2 Presence Of Minor Atypia, But No Evidence Of Malignant Changes CLASS 3 Wider Atypia, May Be Malignant CLASS 4 Few cells are malignant, need for biopsy. CLASS 5 All cells are definitely malignant, need for biopsy.
192

Toluidine blue stain

It is used as an extra tool for the identification of patients suspected with oral cancer lesions.
Toluidine Blue is a cationic metachromic dye which selectively binds to the free anionic groups such as sulphate, phosphate and carboxylate radicals of large molecules. It is used as an in vitro nuclear stain, binding the phosphate groups of nucleic acids.

The sensitivity and specificity of toluidine blue as test for early detection of oral cancer is adequate. Although 100% of cancers may stain, most studies show that only 50% or less of dysplasias are detected by this technique. One per cent of toluidine blue mouthwash has been promoted by FDI in screening for oral mucosal malignancy and potentially malignant lesions in high-risk individuals and population groups, to be confirmed by a biopsy examination.
195

Toluidine blue may be indicated to diagnose leukoplakic lesions or dysplasia; differentiate a traumatic or inflammatory ulcer from cancer; determine the margins of resection prior to excision; and demonstrate a small second primary or satellite lesion adjacent to a larger lesion. However, since toluidine blue does not stain normal mucosa, it is not of value in the diagnosis of tumors which spread without involving the overlying mucous membrane

196

Study of the patient's saliva after irrigation of the mouth with Gey's balanced salt solution may be a useful screening test for squamous cell or epidermoid carcinoma in the oral cavity. Likewise, the topical application of toluidine blue, an acidophilic meta chromatic nuclear stain, helps differentiate areas of carcinoma in situ or invasive carcinoma from normal tissue. However, these two procedures, the mouthwash technique and the toluidine blue test are not a substitute for biopsy and a negative smear does not preclude the presence of cancer.

197

The Mouthwash Technique

A large majority of oral neoplasm's are squamous cell or epidermoid carcinomas. Since these tumors continually exfoliate malignant cells, it was felt that examination of saliva specimens taken from the entire oral cavity following irrigation with some form of mouthwash might be an effective screening test for oral cancer. Numerous mouthwash solutions have been tested: Normal saline solution, which is not truly osmotic, was found unsatisfactory for oral irrigation; cells suspended in this preparation generally absorbed the fluid and burst within a few minutes, making cytological evaluation impossible.
198

Then, at the suggestion of the late Dr. Charles M. Pomerat, Gey's balanced salt solution, a Simple culture fluid containing various amounts of salts normally found in most cells was tested and found to be a successful mouthwash irrigant.

199

Computed tomography scan

CT scan is a diagnostic imaging procedure that uses a combination of radiography and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically of the body.
A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general radiographs.

200

COMPUTED AXIAL TOMOGRAPHY

To help tissues show up better, patient may receive an intravenous injection of dye (also called a contrast agent) either before your test or between a first and second set of pictures. CAT scans can identify tumors that are much smaller than those that can be seen with an X-ray.

201

ULTRASONOGRAPHY
This is a diagnostic technique, which uses high-frequency sound waves to create an image of the internal organs. This image is formed from the echoes of the sound waves on the surface of the organs. Abnormal tissue masses and organs reflect sound waves differently.

202

Magnetic Resonance Imaging (MRI):

This is a diagnostic procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body.

The test is especially helpful in finding cancer that has spread to the other parts of the oral cavity.

203

Patient may have an injection of dye before an MRI, but this technique is used less often than with CT scans. MRI takes longer than CT scans and requires patient to lie still within a tube while the images are made. All metal objects must be removed prior to an MRI so that they are not attracted to the magnets.

204

CHEMILUMINISCENCE
A chemiluminescent illumination system is used to examine the oral mucosa and is available commercially as VIZILITE. The technique is painless, and may ultimately identify suspicious lesions missed during visual examination of the patient. Patient is asked to use 1% acetic acid as a 30 second application or mouth rinse, which prepares the tissue for easy diagnosis.

205

206

The light source is a torch like tube, which when bent, activates the light for the oral inspection. Dysplastic epithelium under the blue-white chemiluminescent light appear whitish or grayish where as the normal epithelium, takes on a blue hue. Recently ViziLite Plus has been introduced which contains toluidine blue dye to assist in diagnosis of early cancerous lesions

207

Use of micronuclei
Since the formation of micronuclei in the eukaryote cells is an end point of chromosomal damage or segregation errors (Geard et al 1990) the presence of micronuclei reflects a genotoxicor carcinogenic exposure. Due to its association with chromosomal aberrations, micronuclei have been used since 1937 as an indicator of genotoxic exposure, based on the radiation studies conducted by Brenneke and Mather (Heddle etal. 1983).

The assay is reliable and technically easy to perform. The direct correlation between the micronuclei formation and genomic damage make the micronuclei assay an efficient alteration to the metaphase analysis (Fenech 1990)
208

Latest oral cancer diagnostic techniques

Fluorescence spectroscopy

Salivary transcriptome diagnostics

Mitochondrial assays Oral fluid nanosensor test Tissue fluorescence imaging Onco-chips

209

210

Examination technique of the mouth

211

212

Levels of Prevention
Levels of prevention Preventive services Services provided by the individual Health promotion
Periodic visits to dental office.

Primary Specific protection

Avoidance of known irritants

Demand for preventive services

Services provided by the Dental health education Avoidance of known programs irritants community
Promotion of research

Services provided by the Patient education Recall reinforcement dental professional

Removal of known irritants

213

Primary Prevention: Protection

Health

Promotion and

Specific

Oral cancer prevention can be attempted at a primary level in clinics, hospitals and in larger population groups. Educational approach. Regulatory or legal approach Service approach. De- addiction programmes

214

Health education: Health education should be imparted to masses with the help of various communication media like television, radio, newspapers, films posters, folk dramas and lecture demonstration series.

Health education can encompass the following aspects:

a. Programmes to educate adolescents including school children against tobacco use with the aim of preventing them from acquiring any tobacco taking in any form of habits.
215

b. Educational programmes for current tobacco users to stop or decrease their use of tobacco including their family members. c. People should be educated about warning signals of oral cancer so that they can do the self-examination and report at the earliest for necessary investigation and required treatment.

216

d. The importance of regular oral check-up by a qualified dental surgeon should be emphasized. e. Importance of good oral hygiene and role of diet and nutrition in oral cancer prevention should be emphasized. f. Importance of various sources of protein, vitamins, minerals, and trace elements, balanced diet, as well as the right method of cooking and preserving the nutrient of food items is not well understood by people, hence these aspects should be stressed.
217

Other means of controlling tobacco use besides educational programmes are restrictive measures and legislative measures which are seen as country's long term tobacco control policy.

In 1965 USA legislation was passed requiring cigarette packages to carry a health hazard warning. In India 1975 cigarettes act was passed. In India 2003 , prohibition of smoking in public places came into force.

218

National prevention programme 1976

Prohibit sale of tobacco to minors Place warning signs at places where tobacco is sold , and on products Prohibit advertising Restrict smoking in enclosed public places Increase taxes Regulate content of tobacco products

219

In 2003, the Centre passed The Cigarettes and Other Tobacco Products (Prohibition of Advertisement and Regulation of Trade and Commerce, Production , Supply and distribution) Act,2003, replacing the single-faceted Cigarettes (Regulation of Production, Supply and Distribution) Act, 1975 with more effective provisions applicable to the whole of India.

220

Health minister A Ramadoss had earlier announced that pictorial warnings of a skull and cross bones and the photograph of a dead person be implemented on all tobacco products.

It will now be compulsory for packets of cigarettes, bidis and chewing tobacco to carry pictorial warning to discourage tobacco consumption, even though the controversial "skull and cross bones" image is optional. 8th Sept 2007.

221

Service approach
The active search for disease among apparently healthy people is a fundamental aspect of prevention. This is embodied in screening. Biopsy technique, Exfoliative cytology or Toludine blue staining.

222

Chemoprevention
Primary prevention effort currently in progress. It is a prescription approach where selected synthetic and natural substances are administered with the purpose of reducing cancer risk, as opposed to proscription approach such as tobacco intervention programme.

223

Levels of prevention
Preventive services Services provided by the individual

secondary
Early diagnosis & prompt treatment Self examination and referral Utilization of dental services

Periodic screening and referral Services provided by the community Provision of dental services

Services provided by the dental professional

Complete examination Biopsy Complete excision

224

Secondary Prevention Screening Early detection and referral. Community-level early detection of oral cancer programmes by primary health care givers should be taken to detect precancerous lesions and to educate those with such lesions against tobacco use.

225

Screening for Oral Cancer: Key to Early Detection at Community Level

Screening the search for unrecognized disease or defect by means of rapidly applied tests, examination or other procedures in apparently healthy individuals
Screening is useful for diseases where the time lag between the diseases onset and its final critical point is sufficiently long to be suitable for population screening.

226

Owing to the high incidence of oral cancer every year especially in south-east Asian countries, including India, and the high degree of morbidity and mortality resulting from with or without treatment of oral cancer, many of which are diagnosed, detection of oral cancer in its earliest stages assumes prime importance.

227

It is the key to increase the survival rates of patients with oral cancer with an improved quality of life. A sore that bleeds easily or does not heal A colour change of the oral tissue A lump thickening, rough spot, crust, or small eroded area Pain, tenderness, or numbness anywhere in the mouth or on the lips.

228

Dentists can perform quick, painless tests, such as a brush biopsy in which tissue specimens, taken from the mouth by a brush, undergo computer analysis to determine the presence of precancerous or cancerous cells.

This test may also help determine the need for a surgical biopsy or other follow-up.

229

Adults can also take an active role in the early detection of oral cancer by doing self-examinations. This means looking into a mirror and checking the lips, gums, cheek lining, and tongue as well as the throat, floor, and roof of the mouth for signs of the disease.

230

If any of these signs or symptoms is noticed, contact the nearby dentist immediately for a professional examination. When diagnosed early, survival rate for oral cancer is high. However, a major problem is that in its earliest most treatable stages, oral cancer generally causes no pain or discomfort and cannot always be diagnosed visually.

231

Knowing the risk factors and taking steps to prevent potentially cancerous lesions from developing can go a long way toward limiting the influence of oral cancer that could have on the peoples life.

People should be encouraged and motivated to join hand with that of the health professionals, especially of dentists in maintaining a good oral health for life.

232

Screening Guidelines for Low-risk Individuals

The two most common methods of screening for oral cancer are visual inspection and cytology, neither of which has been shown to reduce mortality from this disease.
It has been stated that, although screening can lead to early detection, there is insufficient evidence to recommend for or against routine screening for oral cancer. American Cancer Society has no official guidelines for oral cancer detection; however, it encourages primary care physicians to perform an examination of the whole mouth as part of a routine cancer-related check-up.
233

Screening Guidelines for High-risk Individuals United States Public Service Task Force recommends a regular dental examination in patients at high risk of oral cancer. It also suggests annual examinations by a physician or a dentist to screen for oral cancer in patients older than 60 years with risk factors such as smoking and heavy drinking.

234

These recommendations are supported by large, foreign studies of oral cancer screening, which show that primary care physicians can detect premalignant lesions and early cancer in high-risk patients.

With the exception of the Kerala study (clustredrandomized controlled setting, started in 2000), no controlled trials have been undertaken recently to demonstrate the effect of oral cancer screening on mortality or on interim outcomes (e.g. reducing the incidence on invasive disease).
235

An update of these trial reports after completing two rounds of screening oral cancer mortality rates were similar in the screened and unscreened study groups. No other randomized controlled trials, meta-analyses, or systematic reviews were found on the harms of screening or the benefits of early treatment.

236

Levels of prevention
Preventive services Disability limitation
Utilization of dental services

Tertiary
Rehabilitation
Utilization of dental services

Services provided by the individual

Services provided Provision of dental services by the community Services provided by the dental professional
Chemotherapy Radiotherapy Surgery

Provision of dental services

Maxillofacial & removable prosthodontics Plastic surgery Speech therapy

237

Tertiary Prevention
Surgery: Surgery may be a primary treatment or combined with radiotherapy.

Surgery is generally indicated for tumours involving bone tumours that lack sensitivity to radiation, recurrent tumours etc. Surgery may involve mandibulectomy, resection etc. Radical neck dissection may be conducted as a part of an en block resection of tumours with lymph node metastasis.
238

Radiotherapy: Radiotherapy is the treatment of choice and it is a main modality for treating malignant lesions. The general principle of radiotherapy is to deliver uniform dose of radiation to all parts of the tumour bearing areas (tumour bearing zone). Intraoral therapy doses vary from 5000 rad, 15 fractions/3 weeks to 5500 rad 20 fractions/4 weeks depending upon the size of the lesion. Their spacing of radiation dose varies with type and energy of the radiation.

239

Four radiotherapy techniques are there: 1. External radiation 2. Perioral radiation 3. Interstitial radiation 4. Surface radiation.

240

Chemotherapy: Chemotherapy is the use of chemical substances to treat disease. In its modern day use, it refers primarily to cytotoxic drugs used to treat cancer. The era of chemotherapy began in the 1940s with the first uses of nitrogen mustard and folic acid inhibitors.

241

This is considered in patients with advanced tumours or recurrent diseases in whom surgery or radiation is unlikely to result in cure. Chemotherapy is used as induction therapy prior to local therapies, as simultaneous chemoradiotherapy, and as adjuvant chemotherapy after local treatment.

The targeted-therapy revolution has arrived, but the principles and limitations of chemotherapy discovered by the early researchers still apply.
242

To select the most appropriate drug it is necessary to know the range of activity against disease for the various drugs and to use those which have the minimum toxicities in relation to the particular patients. 1. Each drug in the combination should have been demonstrated to have some activity on its own against the tumour. 2. Drugs with similar mechanism of action should not be combined. 3. As far as possible major dose limiting toxicity of each drug should differ from that of the other components in the combination. 4. There should be no known adverse interaction between the drugs.

243

244

245

Palliative care
Palliative care (from Latin palliare, to cloak) is any form of medical care or treatment that concentrates on reducing the severity of disease symptoms, rather than striving to halt, delay or reverse progression of the disease itself or provide a cure. The goal is to prevent and relieve suffering and to improve quality of life for people facing serious, complex illness such as in case of oral cancer.

246

The goals of palliative treatment are extremely concrete: Relief from suffering, Treatment of pain and other distressing symptoms, Psychological and spiritual care, A support system to help the individual live as actively as possible, and A support system to sustain and rehabilitate the individual's family. will enhance quality of life, and may also positively influence the course of illness;
247

Role of dentist in detecting and preventing oral cancer

Dentists hold a vital role in the prevention and early detection of oral cancer. This is primarily due to their familiarity with the structures and health of the oral cavity, its associated tissues, and to the regularity with which their patients attend for routine examination.

248

Screening and examination are both elements of dental practice routine. These two activities are unquestionably vital ways in which practitioners can help detect individuals with unhealthy lifestyles, as well as the earliest signs of the disease, permitting the greatest opportunity for successful resolution and preventing progression to advanced lesions. As a profession we must apply ourselves with renewed vigour at all levels of prevention and intervention.
249

Population-based cancer registries: invisible key to cancer control

Two decades ago, International Agency for Research on Cancer came to the conclusion that population-based cancer registries are an essential part of any rational programme of cancer control.
However, cancer registries are susceptible to a range of welldocumented problems.

Nevertheless, where well-resourced registries exist, their role is expanding and fulfils some vital functions.
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The traditional but important function of population-based cancer registry is to monitor the burden of cancer and the trends in the frequency of cancer in the population. Projections of cancer frequency along with the assumed trends in risk factors and interventions are essential for planning cancer services. Cancer registration data are also used to assess variations in frequency of cancer between and within countries according to age and sex, and sometimes according to ethnic origin, occupation, socioeconomic status, and area of residence.
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Variations in the frequency of patients with cancer between populations and of migrants lead to hypotheses about the causes of cancer. The effect of primary prevention campaigns can be monitored by looking at trends of risk factors, frequency, and ultimately based on the trends in cancer frequency.

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Cancer registry data are used to monitor cancer-screening programmes by observing proportion of patients detected by screening and shifts in stage distribution. The effectiveness of treatment is best monitored by assessing the survival trends.

Cancer registries can supply a suitable population sample for more detailed, unbiased studies of cancer care based on review of medical records. Involvement in genetic counselling is an important new role of cancer registries, subject to the written informed consent of any living relatives.

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Public health approach to oral cancer prevention based on Ottawa chapter, WHO, 1986.
Build public health policy Restrictions on tobacco and alcohol advertising Fiscal policy: Subsidize costs of healthier choices like fruits, vitamins, NRT Improve labelling on betel nut products. Create supportive environment Smoke free public places, for e.g., cinemas Increase availability of fresh fruits and vegetables.

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Strengthen community action Local community based tobacco cessation activities Establish help lines for population Develop personal skills Health education in schools Incorporate tobacco control activities in school Reorient health services Expand health professionals training in oral cancer prevention Increase health manpower to curb this epidemic Establish evidence based smoking and alcohol preventive services within primary care settings
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Global initiatives in the prevention of oral cancer

The Crete declaration on oral cancer prevention 2005 Who framework convention on tobacco control (WHO FCTC)

Bloomberg initiative to reduce tobacco use

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The crete declaration on oral cancer prevention 2005- A commitment to action

The 10th International Congress on Oral cancer organized by the Hellenic Cancer Society, International Congress on Oral Cancer, Hellenic Association for the Treatment of Maxillofacial Cancer and the World Health Organization was held from 19-24 April 2005 in Crete, Greece.

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The participants from 57 countries emphasized that oral health is an integral part of general health and wellbeing and expressed concern about the neglected burden of oral cancer which particularly affects developing countries with low availability of prevention programs and services for oral health. This culminated in the Crete Declaration on Oral Cancer Prevention 2005 which stated that the following areas of work should be strengthened:

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a) provision of systematic epidemiological information on prevalence of oral cancer and cancer risks in countries, particularly in the developing world. b) promotion of research into understanding the biological, behavioral and psychosocial factors in oral cancer, emphasizing the interrelationship between oral health and general health c) integrating oral cancer information into national health surveillance systems which record chronic diseases and common risk factors. d) dissemination of information on oral cancer, prevention and care through every possible means of communication.
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e) active involvement of oral health professionals in oral cancer prevention through control of risk factors such as tobacco, alcohol and diet. f) training of primary health workers in screening and provision of first-level care in oral cancer.

g) access to health facilities and provision of systems for early detection and intervention, oral health care and health promotion for the improvement of quality of life of people affected by oral cancer.
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WHO framework convention on tobacco control (WHO FCTC)

The WHO Framework Convention on Tobacco Control (WHO FCTC) is the first treaty negotiated under the auspices of the World Health Organization. The WHO FCTC treaty opened for signature on 16 June to 22 June 2003 in Geneva, and when closed, had 168 Signatories, which makes it the most widely embraced treaties in UN history. The WHO FCTC was developed in response to the globalization of the tobacco epidemic.
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The WHO FCTC is an evidence- based treaty that reaffirms the right of all people to the highest standard of health. It asserts the importance of demand reduction strategies as well as supply issues.

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The demand reduction provisions are: Price and tax measures to reduce the demand for tobacco, and Non-price measures to reduce the demand for tobacco, namely: Protection from exposure to tobacco smoke Regulation of the contents of tobacco products Regulation of tobacco product disclosures Packaging and labeling of tobacco products Education, communication, training and public awareness Tobacco advertising, promotion and sponsorship Demand reduction measures concerning tobacco dependence and cessation
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The supply reduction provisions are: To stop illicit trade in tobacco products; To stop sales to and by minors; and, Provision of support for economically viable alternative activities.

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Bloomberg initiative to reduce tobacco use

This initiative, funded by Bloomberg Philanthropies, is the two-year contribution of US$125 million by Michael R. Bloomberg for global tobacco control. It is committed to the scaling up of tobacco control efforts in developing countries, with special emphasis in 15 developing countries (Bangladesh, Brazil, China, Egypt, India, Indonesia, Mexico, Pakistan, Philippines, Poland, Russian Federation, Thailand, Turkey, Ukraine and Viet Nam), where more than two thirds of the world's smokers live and where the health burden from tobacco use is highest.
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Five key partner organizations will implement the Bloomberg Initiative, building national capacity, coordinating activities and providing grants to other organizations, mostly at country level, to promote freedom from smoking.

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BLOOMBERG INITIATIVE

Partner Organizations
Campaign for Tobacco-free kids
Centers for Disease Control and Prevention (CDC) Foundation Johns Hopkins Bloomberg School of Public Health Education/training

Activities
In charge of awarding Bloomberg grants
Monitoring/surveillance, to establish systematic, standardized global surveillance and monitoring of the tobacco epidemic.

The Johns Hopkins Bloomberg School of Public Health will develop training resource materials to help smokers stop and prevent children from starting. Coordination mechanism at country level. It will expand the public-sector support and guidance it already provides to help governments develop national tobacco control plans, pass and enforce key laws and implement effective policies and tobacco control measures.
In charge of awarding Bloomberg grants and 267 global clearing house for tobacco ads.

World Health Organization Tobacco Free initiative (WHO/TFI) World lung Foundation (WTF )

The initiative coordinated by the five key partner organizations will focus on the following four components: Refine and optimize tobacco control programs to help smokers stop and prevent children from starting.

Support public sector efforts to pass and enforce key laws and implement effective policies, in particular to tax cigarettes, prevent smuggling, change the image of tobacco, and protect workers from exposure to other people's smoke.

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Support advocates' efforts to educate communities about the harms of tobacco and to enhance tobacco control activities so as to help make the world tobacco- free. Develop a rigorous system to monitor the status of global tobacco use.

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Guide for tobacco cessation (quitting)

1. Ask patients about the use of tobacco at every visit Regarding use of tobaccocurrent/former/ never Type/form of tobacco, Duration Number Frequency Look for oral signs of tobacco use: Stained teeth Foul smelling breath (halitosis) Gum disease Loose teeth Discoloured patches on the mucosa: white, red, dark precancerous lesions. Record tobacco use status 271

2. Advise patients:

Advice for quitting should be clear, strong and personalized Quitting tobacco use is the most important thing you can do to protect your health. Cutting down while you receive dental treatment is not enough Tobacco use is hurting your oral health, your finances and your familys happiness. Encourage non-users to stay away from tobacco, affirm non-use of tobacco and advise them to never use tobacco in future. Affirm and congratulate those who have quitted the use tobacco and offer support, if required.

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3. Assess the patients readiness to quit: Ask every tobacco user if he/she is willing to quit at this time. If the patient is willing to quit assess the level of dependence. ` Tobacco users who are heavily dependent on tobacco usually have a harder time quitting than less dependent users.

High level of dependence: Individuals who use tobacco within 30 minutes of waking up or those who use it 25 or more times per day. Moderate level of dependence: Individuals who use tobacco later than 30 minutes after waking up or less than 25 times per day. Low level of dependence: Those who neither use tobacco before 30 minutes of waking up nor use it more than 25 times a day

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If the patient is only thinking of quitting but not willing to quit it now than provide a tailored message to increase motivation. If the patient is not prepared to quit shift them to the 5R method. These patients may respond to a motivational intervention built around the 5 Rs Relevance of quitting Risks of continuous tobacco usage Rewards of quitting Roadblocks to quitting, and Repetition at each visit

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4. Assist tobacco users to make a quit plan: Set a firm quit date, ideally within 2 weeks. Get support from family, friends, co-workers. Review past quit attemptswhat helped and what led to relapse. Identify reasons for quitting in writing and keep a copy. Reduce tobacco use during the 2 weeks before quitting.

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5. Arrange for follow-up visits:

Methods: Use revisits, telephone contact or assist the patient in arranging an appointment with his/her physician or a trained community health worker. Timing: Set a schedule. The first follow-up visit should occur within a week of the quit date that is why it is important the patient to set a quit date for few days prior to the revisit date for dental treatment. A second follow-up visit is best within one-month of the quit date. Further follow-up visits are helpful after 3 months, 6 months and 1 year.
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Use of pharmacotherapy There are two main types of pharmacotherapy for tobacco use cessation:

Nicotine replacement therapies (NRT): These replacements lessen the craving and other withdrawal symptoms while the individual learns to stop the behaviours connected with tobacco use. Eventually, though, patients need to give up using nicotine replacement.

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NRTs commercially available in the following forms: Gum Patch Inhalator Sublingual tablet Lozenge Nasal spray Nicotine replacement therapy is an effective aid for tobacco cessation. Tobacco users who are motivated to quit but are dependent on nicotine should be given NRT. NRT should be prescribed for six to eight weeks, in blocks of up to two weeks, contingent on continued abstinence. Obtaining nicotine from NRT is considerably safer than smoke and smokeless tobacco. NRT is safe in stable cardiac disease, but caution is needed for unstable, acute cardiovascular disease, pregnancy or breast-feeding or in those under 18 years of age.

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Antidepressants: These also function as anticraving medications and can be combined with NRTs.

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Tobacco control in India what have we achieved till date ?

The cigarettes Act 1975 made a statutory health warning mandatory on all cigarette packets. Prevention and Control of Pollution Act included smoking in the definition of air pollution. Motor Vehicles Act of 1988 made it illegal to smoke in a public vehicle.

Cables Television Network Amendment Act of 2000 prohibited the transmission of tobacco commercials on cable TV across the country.
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1999: Ministry of railways banned sale of cigarettes and bidis on railway platforms and inside trains. 2001-03: The states of Tamil Nadu, kerala, Andhra Pradesh, Maharashtra, Bihar, Goa and Madhya Pradesh banned the production and sale of gutka and pan masala under the Prevention of Food Adulteration Act.

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The Cigarettes and other Tobacco Products (Prohibition of Advertisement and Regulation of Trade and Commerce, Production, Supply and Distribution) Act, 2003 (COTPA), a comprehensive tobacco control legislation, comes into force on 1st May 2004 . India ratified FCTC on 5th February 2004.

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The Cigarettes and Other Tobacco Products Act, 2003: Significance to Public Health
Section 4: Ban on Smoking in Public Places.
Section 5: Ban on Advertisements of Tobacco Products.

Section 6: Prohibition of Sale of Tobacco Products to and by Minors.

Section 7: Specified Health Warning Labels on all Tobacco Products Increasing Tax and Price of Tobacco Products:

World No Tobacco Day

WNTD stands for World No Tobacco Day, which is celebrated around the world on 31 May every year. It was first suggested by World Health Organization (WHO) in 1987. The 40th anniversary of the WHO, to be a world no-smoking day. Since then, the WHO has supported WNTD every year, with each year linked to a different ills of tobacco related theme.

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Conclusion
Non-communicable diseases including cancer are emerging as important public health problems in India. The major risk factors for these diseases are tobacco, dietary habits, inadequate physical activity, alcohol consumption and infections due to viruses. The greatest impact to reduce the burden of cancer comes from primary prevention. Extensive persuasive health education is needed to be directed to control/reduce the tobacco habit. Nutrition education, safe sexual practices, attention to personal and genital hygiene needs to be imported for increasing public awareness.
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Oral cancer remains a lethal disease for over 50% of cases diagnosed annually. This is largely reflected by the fact most cases are in advanced stages at the time of detection despite easy accessibility of the oral cavity for regular examination. Even for those surviving quality of life remains poor. The removal of known risk factors even after diagnosis may improve the prognosis and there is evidence that such measures may reduce the risk of recurrences and second tumours in existing oral cancer patients. Development of tumour markers with high sensitivity and specificity could assist in surveillance for recurrent disease that contributes to deaths in this high risk group
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National efforts to reduce morbidity and mortality associated with oral cancer must focus on two areas: primary prevention (i.e., reducing risk factors) and early detection. Although persons at high risk for the disease are more likely to visit a physician than a dentist, physicians may be less likely than dentists to perform an oral cancer examination on such patients Thus, all primary-care providers must assume more responsibility for counselling patients about behaviours that put them at risk for developing this cancer, examining patients who are at high risk for developing the disease because of tobacco use or excessive alcohol consumption, and referring patients to an appropriate specialist for management of a suspicious oral lesion.
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Comprehensive education of medical and dental practitioners in diagnosing and promptly managing early lesions could facilitate the multidisciplinary collaboration necessary to detect oral cancer in its earliest stages.

Furthermore, because of the public's lack of knowledge about the risk factors for oral cancer and because this disease can often be detected in its early stages, the public's awareness of oral cancer (including its risk factors, signs, and symptoms) must also be increased.

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Case control studies

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References
Essential Dental Public Health;1st Ed. Blanaid Daly; Oxford University Press. Peter S. Essentials Of Preventive And Community Dentistry. Arya Publishing House 2003,pg 370-416 Community Dental Health; 5th Ed. Anthony Jong; Mosby Publishers Dental Council of India .National oral health survey and fluoride mapping 2002-2003.Pg 101-104,126

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Pine MC. Community Oral Health. 1st edition. Barth Press. 1997. Sankaranarayanan R.Oral cancer in India : an epidemiologic and clinical review. Oral Surg Oral Med Oral Pathol 1990;69(3):325-330. Johnson NW,BAIN Carcinoma of Tobacco and oral Disease. British dent journal 2000;189(4):200-206. Lingen W.Oral cancer screening aids: where is the science ? Oral Surg Oral Med Oral Pathol 2007;103(2):153-154. R Kalyani, Subhashish Das, ML Harendra Kumar Pattern of Cancer in Adolescent and Young Adults A Ten Year Study in India. Asian Pacific J Cancer Prev, 11, 655-659
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D Sujatha, Pragati B Hebbar, Anuradha Pai. Prevalence and Correlation of Oral Lesions among Tobacco Smokers, Tobacco Chewers, Areca Nut and Alcohol Users. Asian Pacific Journal of Cancer Prevention, Vol 13, 2012. Saranath D. Contemporary issues in oral Cancer. Oxford university press 1989, pg 1-29. Shah J, Jhonson Nw, Batsakis J.Oral cancer Martin Dunitz pub 2003, pg 3-33. World Health Organization. Control of oral cancer in Developing countries. Bulletin of the World Health Organization. 1994;62:817830. 294

Thank You

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