Oral cancer seminar

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Seminar OnOral Cancer And Carcinogenesis

Presented ByDr Sourav Malhotra

2nd Year

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CONTENTS

Introduction

Carcinogenesis

Oral Cancer

Epidemiology

Etiological Factors

Clinical Features

Investigations

Treatment

Prognosis

Conclusion

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Neoplasm : It is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissue and persists in the same excessive manner even after the cessation of the stimulus that evoked the change.

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Cancer is the end product of an unregulated proliferation of cells

It results from the accumulation of sequential genetic alterations in precursor cells

Cancer cells do not de differentiate

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Cancers arise from the transformation of single precursor cells into a clone consisting of many daughter cells

All cells within a cancer are not alike

Cancer cells are a heterogeneous population

Each individual cell modifies its behavior and properties and mutates with each cell division

7SARCOMA CARCINOMA(Malignant tumor) (Malignant tumor)

1. Arises from muco-skeletal system such as bones, muscles and connective tissues

They arise from epithelial cells

2. Rare, less than 1 % of cancers Most common, about 90% of cancers

3. Affects younger people also Affects older people

4. Mostly develops inside the bone It infiltrates the nearby structures

5. Have a ball like mass Dose not possess a ball like mass

8SARCOMA CARCINOMA

6. Tends to push nearby structures as arteries, nerves and veins away.

They invade nearby nerves, veins, muscles and blood cells.

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CARCINOGENESIS

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CARCINOGEN

An agent that causes a series of genetic alterations to occur, leading to the formation of cancerous growths.

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Oral carcinogenesis is a highly complex multifocal process that takes place when squamous epithelium is affected by several genetic alterations.

Field cancerization refers to the potential development of cancer at multiple sites .

Hindawi Publishing Corporation, Journal of Oncology Volume 2011, 1-10 .

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4 broad headings

Molecular pathogenesis

of cancer (genes and

cancer)

Chemical carcinogenesis

Physical carcinogens

and radiation carcinogenesis

Biologic carcinogens

and viral oncogenesis

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Molecular pathogenesis of cancer

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EXCESSIVE AND AUTONOMOUS GROWTH

ESCAPING CELL DEATH BY APOPTOSIS:

REFRACTORINESS TO GROWTH INHIBITION: GROWTH SUPPRESSING ANTI - ONCOGENES

DNA DAMAGE AND REPAIR SYSTEM: MUTATOR GENES AND CANCER

INVASION AND DISTANT METASTASIS:

CONTINUED PERFUSION OF CANCER: TUMOR ANGIOGENESIS

AVOIDING CELLULAR AGING: TELOMERES AND TELOMERASE IN CANCER.

CANCER PROGRESSION AND HETEROGENEITY:

Harsh mohan, etiology and pathogenesis of neoplasia: essential pathology; 3rd edition, 247-270.

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Excessive And Autonomous Growth: Growth Promoting Oncogenes

In normal cell growth :

Proto-oncogenes are growth-promoting genes i.e. they encode for cell proliferation pathway.

In cancer :

Activation of growth-promoting oncogenes causing transformation of cell. Gene products of oncogenes are called oncoproteins. Oncogenes are considered dominant since they appear in spite of presence of normal proto-oncogenes.


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REFRACTORINESS TO GROWTH INHIBITION:

In normal cell growth . • Anti-oncogenes are growth-

inhibiting or growth suppressor genes.

In cancer • Removal of brakes from the

growth.• Continues unchecked. • Eg – RB gene, TP53


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In normal cell growth

Apoptosis regulatory genes control the programmed cell death.

In cancer

Abnormal apoptosis regulatory genes which may act as oncogenes or anti-oncogenes. Accordingly, these genes may be active in dominant or recessive form.BCL2, CD95.


ESCAPING CELL DEATH BY APOPTOSIS:

Avoiding Cellular Aging

In normal cell

• Telomerase is the RNA enzyme that helps in reparing the damaged DNA and maintains normal telomere length in successive cell division.

• After repetitive mitosis for a maximum of 60-70 times, telomeres are lost in normal cells and the cells cease to undergo mitosis.

In cancer

• In most malignancy telomerase enzyme is upregulated and hence telomerase length is maintained. Cancer cells avoid aging and mitosis does not slow down or ceases.

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19Continued Perfusion Of Cancer; Tumor Angiogenesis

• Cancer cells can only survive if the cancer cells are adequately nourished.

• Neovascularisation in the cancer not only supplies the tumor with oxygen and nutrients but the newly formed endothelial cells also elaborate a few growth factors for progression of primary as well as metastatic cancer.

• Eg- VEGF.

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Invasion And Metastasis

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DNA DAMAGE AND REPAIR SYSTEM:

In normal cell growth –

DNA repair genes are those normal genes which regulate the repair of DNA damage that has occurred during mitosis and also control the damage to proto-oncogenes and antioncogenes.

In cancer

Failure of DNA repair genes and thus inability to repair the DNA damage resulting in mutations, this defect is passed to the next generation.

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CHEMICAL CARCINOGENESIS

The induction of cancer by chemical carcinogens occurs after a delay—weeks to months in the case of experimental animals, and often several years in man.

2 sequenti

al stages:

Initiation

Promotion

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INITIATION OF CARCINOGENESIS

First stage.

The change can be produced by a single dose of the initiating agent for a short time, though larger dose for longer duration is more effective. The change so induced is sudden, irreversible and permanent.

Chemical carcinogens acting as initiators of carcinogenesis can be grouped into 2 categories

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Direct-acting carcinogens. These are a few chemical substances (e.g. alkylating agents, acylating agents) which can induce cellular transformation without - metabolic activation.

Indirect-acting carcinogens or procarcinogens. require metabolic conversion within the body so as to become ‘ultimate’ carcinogens having carcinogenicity e.g. polycyclic aromatic hydrocarbons, aromatic amines, azo dyes, naturally-occurring products and others.


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PHYSICAL CARCINOGENESIS

2 groups:

Radiation,

Ultraviolet light

Ionising radiation.Non-radiation physical agents are the various

forms of injury and are less important.

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ULTRAVIOLET LIGHT.

The main source – sunlight.

Uv light penetrates the skin - few millimetres only so that its effect is limited to epidermis.

Induction of mutation

Inhibition of cell division

Inactivation of enzymes

Sometimes causing cell death.

Such UV-induced DNA damage in normal individuals is repaired, while in the predisposed persons who are excessively exposed to sunlight such damage remain unrepaired.

The most important biochemical effect of UV radiation is the formation of pyrimidine dimers in DNA.

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• Ionising radiation of all kinds like X-rays, α-, β- and γ-rays, radioactive isotopes, protons and neutrons can cause cancer in man.

• Radiation damages the DNA of the cell by:• DIRECT EFFECT• INDIRECT EFFECT

IONISING RADIATION.

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Mechanical injury to the tissues such as from stones in the gallbladder, stones in the urinary tract, and healed scars following burns or trauma, has been suggested as the cause of increased risk of carcinoma in these tissues but the evidence is not convincing.

Non-radiation Physical Carcinogenesis

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BIOLOGIC CARCINOGENESIS

The epidemiological studies on different types of cancers indicate the involvement of transmissible biologic agents in their development, chiefly viruses.

Other biologic agents :• Parasites. Schistosoma haematobium • Fungus. Aspergillus flavus • Bacteria. Helicobacter pylori

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VIRAL CARCINOGENESIS

Oncogenic viruses can be transmitted by one of following ways.

Vertical transmission: when the infection is genetically transmitted from infected

parents to offsprings.

Horizontal transmission. viral infection passes from one to another by direct

contact, by ingestion of contaminated water or food, or by inhalation as occurs in most

contagious diseases.

By parenteral route such by inoculation as happens in some viruses by inter-human spread and from animals and insects to

humans.

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Tumor Suppressor Genes

Group of genes that encode proteins with negative affects on cell division.

These genes products inhibit the cell cycle when DNA damage occurs.

This damage may develop as a consequence of exposure to carcinogens or infection with oncogenic virus.

If damage is severe and non reparable, the TSG proteins may push the cell into programmed cell death or apoptosis.

Imp gene which operates in this fashion is p53.

This is activated when DNA is damaged.

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This inhibition prevents

the cell

from

progressing into S

phase.

If p53 is mutated in both

alleles or one allele is

mutated and the other is not

expressed, there are no

brakes on the cell cycle and

mitosis progresses

unchecked.

Most

oral carcinom

as

have p 53 mutations.

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Cell Adhesion Molecules

Oral carcinoma have been shown to downregulate a variety of integrins that are necessary for attachment to cells and ECM proteins and proteoglycans.

It is a biologically contrived event that allows the stealthy cancer cells to pass through the extracellular matrix by virtue of cell:matrix adhesion molecule expression with internal signaling that promotes motility.

Oral malignancy is characterized by the ability of cancer cells to migrate, adhere to vascular endothelia and enter vessels, which transport tumor cells to distant sites.

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Loss of alpha 2, 3, 4, 5 and beta 1 as well as the 64 dimer is seen in carcinomas and the loss of these adhesions probable serves to migrate immobolization.

Other adhesion molecules that are under expressed and presumed to be correlated with invasiveness and metastasis are E-cadherin, the catenins and the hyaluronate binding molecules CD44.

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Oral Squamous Cell Carcinoma

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More than 95% of the carcinomas of the oral cavity are of squamous cell type, in nature.

They constitute a major health problem in developing countries, representing a leading cause of death.

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Epidemiology

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Worldwide oral carcinoma, is one of the most prevalent cancers

One of the ten most common causes of death

Eleventh most common cancer worldwide

High incidence in • Indian

subcontinent• Australia• France• Brazil • Southern Africa

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Males

Eighth most common cancer

4% of total body cancers

Females

Fifteenth most common cancer

2% of all body cancers

Scully et al, American Journal of Dentistry, Vol. 21, No. 4, August, 2008

44Oral cancers accounts for 2% of cancer deaths in males and 1% of cancer deaths in females. Approximately 95% of oral malignancies are Squamous Cell Carcinoma.

95% of oral squamous cell carcinoma occur in people older than 40 years.

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• Most common cancer in India

• Four in ten of all cancers are oral cancers

• Annually 1,30,000 people succumb to oral cancer in India

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In India higher incidence is due

to:

Use of tobacco in various forms

Consumption of alcohol

Low socioeconomic

conditions

Poor hygiene Poor diet

Rampant viral infections

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Etiological factors

Tobacco Alcohol

Viruses

Betel quid Candida HIV

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Tobacco

Tobacco was first introduced to western civilization by Spanish explorers of America in 16th century.

Cigarettes were first made in Spain in mid 17th century.

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Constituents of tobacco in cigarette

are:

500 mg of gas (92%)

Co2

O2

Nitrogen

Carbon monoxide

Tar ( aromatic hydrocarbo

ns)Nicotine

Thiocynate

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Cancer risk and Smoking Numerous studies have shown that some hydrocarbons isolated from tobacco products have induced buccal carcinomas.

Benzopyrene, the most potent of these binds to nucleoproteins and is mutagenic as well as carcinogenic.

Certain enzymes can metabolize hydrocarbons into more potent carcinogenic form.

Oral cancer, Sol Silverman, etiology and predisposing factors; 3rd edition: 7-39.

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Aryl hydrocarbon hydroxylase(AHH), an enzyme produced in human leukocytes, increases the risk of carcinoma.

Smokers who produce large amounts of this enzyme may have a higher risk of developing carcinoma in tobacco zone sites.


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Synergistic effects of tobacco and alcohol

Dehydrating effects of alcohol

on mucosa

Increases mucosal permeability

Here starts the effects of potent carcinogens

in alcohol and tobacco.

Acetaldehyde, which is the alcohol metabolite, has been identified recently as a tumor promoter.

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BETEL QUID The use of betel quid

with both areca nut and tobacco, is associated with a much higher relative risk of oral cancer between 8-15 times.

Bq chewing produces ROS

It is detrimental to oral mucosa

Can be directly involved in tumor initiation process, by inducing mutation

It also makes the mucosa susceptible to BQ ingredients and environmental toxicants

Indian Journal of Cancer | April–June 2006 | Volume 43 | Issue 2

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The production and release of ROS occurs under alkaline conditions during the auto oxidation of areca nut in the BQ chewer’s saliva

Attacking the salivary proteins and oral mucosa, leading to structural change in the oral mucosa, that may facilitate the penetration by other BQ ingredients and environmental toxicants


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Iron deficiency, especially the severe, chronic form known as the Plummer-Vinson or Paterson-Kelly syndrome , is associated with an elevated risk for squamous cell carcinoma of the esophagus, oropharynx, and posterior mouth.

Malignancies develop at an earlier age than in patients without iron deficiency anemia.

People who are deficient in iron tend to have impaired cell-mediated immunity, and iron is essential to the normal functioning of epithelial cells of the upper digestive tract.

IRON DEFICIENCY

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In deficiency states, these epithelial cells turn over more rapidly and produce an atrophic or immature mucosa.

Intertwining fibrous bands of scar tissue also may develop within the esophagus of severely affected patients (esophageal webs).

Patients with such esophageal webbing seem to be especially susceptible to malignant transformation.


SYPHILIS

Syphilis (tertiary stage) has long been accepted as having a strong association with the dorsal tongue carcinoma.

The arsenical agents and heavy metals that were used to treat syphilis before the advent of modern antibiotic therapy have carcinogenic properties themselves and may have been responsible for some of the earlier cancer development in this disease.

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ONCOGENIC VIRUSES

Viral agents capable of integration into the host’s genetic material may be particularly dangerous and potentially could commandeer the host’s ability to regulate normal growth and proliferation of the infected cell.

The oncogenic viruses may immortalize the host cell, thereby facilitating malignant transformation.

In the past, retroviruses, adenoviruses, herpes simplex viruses (HSVs), and human papillomaviruses (HPVs) all have been suggested as playing a role in the development of oral carcinoma.


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It appears, however, that HPV is the only one still implicated, not only in oral cancer but also in carcinoma of the pharyngeal tonsil, larynx, esophagus, uterine cervix, vulva, and penis.

HPV subtypes 16, 18, 31, and 33 are the strains most closely associated with dysplasia and squamous cell carcinoma.

Primarily involve two virally encoded proteins: (1) E6 (2) E7

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IMMUNOSUPPRESSION

Immunosuppression may play a role in the development of at least some malignancies of the upper aerodigestive tract.

Without effective immunologic surveillance and attack, it is thought that newly created malignant cells cannot be recognized and destroyed at an early stage.

Persons with AIDS and those who are undergoing immunosuppressive therapy for malignancy or organ transplantation are at increased risk for oral squamous cell carcinoma and other head and neck malignancies, especially when tobacco smoking and alcohol abuse are present.


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ONCOGENES AND TUMOR SUPPRESSOR GENES

Oncogenes and tumor suppressor genes are chromosomal components capable of being acted on by a variety of causative agents.

Normal genes, or protooncogenes, are transformed into activated oncogenes in certain malignancies through the actions of viruses, irradiation, or chemical carcinogens.

Once oncogenes are activated, they may stimulate the production of an excessive amount of new genetic material through amplification or overexpression of the involved gene.

Oncogenes probably are involved in the initiation and progression of a wide variety of neoplasms, including oral squamous cell carcinoma.

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Candida Candida albicans can

induce epithelial proliferation and can produce carcinogens from procarcinogens.

Chronic hyperplastic candidosis presents as nodular or speckled-white mucosal plaques are potentially malignant oral epithelial lesions.


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CLINICAL FEATURES

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INTRAORAL CARCINOMA

The most common site for this carcinoma is the tongue, usually the posterior lateral and ventral surfaces.The oral floor is affected almost as frequently in men but is involved much less commonly in women

66Other sites of involvement are the soft palate, gingiva, buccal mucosa, labial mucosa, and hard palate.

Carcinoma of the tongue accounts for more than 50% of intraoral cancers in population studies in the United States .

Two thirds of lingual carcinomas appear as painless, indurated masses or ulcers of the posterior lateral border; 20% occur on anterior lateral or ventral surfaces, and only 4% occur on the dorsum

68Tumors of the maxillary alveolar ridge may extend onto the hard palate .

If the tumor is adjacent to a tooth ,then it may mimic periodontal disease or a pyogenic granuloma.

Gingival carcinoma often destroys the underlying bone structure, causing tooth mobility.

This lesion may not become clinically evident until after tooth extraction, when it proliferates out of the socket to mimic the hyperplastic granulation tissue of epulis granulomatosa.

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Oral squamous cell carcinoma has a varied clinical presentation, including the following:

• Exophytic• Endophytic• Leukoplakic• Erythroplakic• Erythroleukoplakic

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The surface is often ulcerated, and the tumor feels hard (indurated) on palpation

An exophytic lesion typically has a surface that is irregular, fungating, papillary, or verruciform, and its color may vary from normal to red to white, depending on the amount of keratin and vascularity .

71The endophytic growth pattern has a depressed, irregularly shaped, ulcerated, central area with a surrounding “rolled” border of normal, red or white mucosa.

The rolled border results from invasion of the tumor downward and laterally under adjacent epithelium.

This appearance is not unique to oral carcinoma because granulomatous lesions, such as deep fungal infections, tuberculosis, tertiary syphilis, oral lesions of Wegener’s granulomatosis or Crohn’s disease, and chronic traumatic ulcers, may look similar.

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Squamous cell carcinoma, metastatic spread. Potential sites for metastatic spread of oral carcinoma to regional lymph nodes.

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International Union against Cancer. TNM classification of malignant tumours. 5th ed. New York: John Wiley and Sons Inc, 1997.

Staging of OSCC

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Investigations

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Vital staining

Visualisation adjuncts

Cytology

Molecular methods

Nanotechnology

Biomarkers

DIAGNOSTIC ADJUNCTS

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• Identify mucosal lesion with the presence of high-risk molecular patterns that have the potential for progression to cancer

• Assess the extent of a lesion and assess margins of OSCC

• Assist in biopsy site selection and to accelerate the decision to biopsy

• Assess the outcome of treatment of oral dysplasic lesions and follow-up postcancer treatment

TOLUIDINE BLUE

Acidophilic metachromatic dye -stains dysplastic and malignant lesions. It stains acid components in DNA and RNA which are more in dysplastic cells.

Procedure: 1% acetic acid is applied on the lesion for 20 second and is rinsed with water followed by 1% toludine blue application for 10-20 seconds and decolorized with 2% acetic acid for 20-30 seconds.

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PHOTOSENSITIZERS

It is based on the accumulation of a photosensitive dye in premalignant and malignant lesions. A certain period of time after the dye has been administered, tumor tissue may contain more of the sensitizer then the surrounding normal tissues. When tissue containing the sensitizer is exposed to light of a proper wavelength, fluorescence can potentially be utilized to detect tumors.

Healthy tissue, showing ordered and dense collagen fiber network in blue. Malignant lesion, showing further collagen loss and inflammatory exudates (red).

AGENTS AMINOLEVULINIC ACID(ALA)

PORFIMER SODIUM (PHOTOFRIN)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866626/figure/F8/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866626/figure/F10/

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VIZILITE

Chemi –Light-Stick

1% acetic acid Rinse with 1% acetic acid

Normal-blueAbnormal- acetowhite

Lesion examination

under chemiluminesce

nt light

Wavelength430,540,58

0 nM

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VELSCOPE

BLUE LIGHT400-460nM(UV)

NORMAL-PALE GREEN

ABNORMAL- LOSS OF

AUTOFLUORESCENCE

DISADVANTAGS

LOW SIGNAL-NOISE RATIO

LIMITED TISSUE

PENETRANCE

MUTAGENICITY ON USING

UV LIGHT

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OCT is a high-resolution optical technique that permits noninvasive imaging of surface and subsurface tissues

Based on low-coherence interferometry, using broadband light to provide crosssectional, high-resolution subsurface tissue images , tissue penetration depth of 1 mm to 2 mm.

Optical coherent tomography

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Minute changes like tissue architecture, mineralization, vascularity, angiogenesis and perfusion

3D images can be constructed

Detects multiple lesions

Information on potential regions of interest

Mapping the lesion extent and boundaries

Noninvaasive, good patient acceptance

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Advantages:

• Quick, painless, simple and non-invasive.

• Helps in screening large samples.

ORAL Brush

Biopsy:

• It makes use of a cyto brush with firm bristles that obtain individual cells from full thickness of the stratified squamous epithelium.

• It is significantly more accurate than other cytologic technique used in the oral cavity.

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BIO MARKERS

The most predictive of the molecular markers thus far available and assessed in OSCC development include the TSG p53 protein expression, chromosomal polysomy (DNA ploidy), and changes (termed loss of heterozygozity; LOH) in chromo-somes 3p or 9p (probably due to changes in the TSG p16).

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DNA ploidy

DNA ploidy is the measurement of nuclear DNA content.

Normally, a non-dividing somatic cell contains a diploid amount of DNA in 23 pairs or 46 chromosomes.

Just before cell division, the DNA is doubled and in mitosis; the 23 pairs of chromosomes are evenly distributed to two daughter cells.

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In somatic cells, if a doubling of the DNA during S-phase occurs without a subsequent cell division, the nucleus will then contain quadruples of the DNA, making the cell tetraploid.

Multiple copies of DNA in excess of diploidy is termed polyploidy. If the chromosomes are not uniformly distributed to the daughter cells or if parts of chromosomes become detached, the chromosomal segregation during mitosis is termed unbalanced, a situation termed aneuploidy and commonly observed in many cancers.

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DNA ploidy can be measured fairly simply with automated image

cytometry of nuclei obtained from routinely processed tissue samples.

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Elastic scattering spectroscopy requires light to be fired into tissue in a short burst and the resulting signal is detected by fibers and fed into a spectrometer interfaced with a computer.

When light enters the tissue it may be elastically scattered, inelastically scattered, or absorbed.

The amount the light scatters depends on nuclear size, shape and orientation.

In addition, light will be scattered by intracellular organelles and there will also be other changes depending on tissue thickness.

Elastic scattering spectroscopy

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Trimodal spectroscopy uses three independent optical diagnostic techniques (fluorescent spectroscopy, diffuse scattering spectroscopy and elastic scattering spectroscopy) to achieve better results, reaching sensitivity and specificity of 96% in differentiating between normal oral mucosa and dysplasia and OSCC. Tri-modal spectroscopy, although having the advantage of being accurate is however, expensive and time-consuming.

Trimodal spectroscopy

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Quantum dots

Quantum dots are particles of one nanometer in diameter whose action is based on the fluorescence phenomenon.

They absorb photons of white light within their core and re-emit nanochromatic light at a specific wavelength, and the re-emitted light is so bright that it is possible to detect it even if only one cell-crystal complex is excited.

Quantum dots absorb light over a wide spectrum so it is possible to excite many dots with a single light source, each emitting a different color, thereby allowing detection of multiple markers at the same time

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Saliva-based oral cancer diagnostics

Exfoliative cell samples have been used to detect genetic alterations in the oral epithelium of patients at high risk from oral cancer and to detect microsatellite alterations in OSCC.

Promoter hypermethylation patterns of TSG p16, O6-methylguanine-DNA-methyltransferase, and death-associated protein kinase have been identified in the saliva of head and neck cancer patients.

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Also high salivary counts of Capnocytophaga gingivalis, Prevotella melaninogenica and Streptococcus mitis have been found in patients with OSCC

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RECENT ADVANCES Doppler OCTNuclear magnetic resonance spectroscopy ChromoendoscopyNarrow band imaging (NBI)Immunophotodiagnostic techniquesDifferential path length spectroscopy 2 photon fluorescence2nd harmonic generationTerahertz imaging.

94Pretreatment Oral and Dental Assessment

The oral assessment is

needed to identify conditions that

should be treated prior to cancer

therapy to:

Identify oral involvement by cancer

Reduce the risk or severity of

complications

Reduce the risk of infection involving the dentition and mucosa

Minimize and manage the complications of

hyposalivation.

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Treatment

96Chemotherapy

Chemotherapy is used as induction therapy prior to local therapies, simultaneous chemoradiotherapy (concurrent CCRT), and adjuvant chemotherapy after local treatment.

The objective of induction chemotherapy is to promote initial tumor reduction and to provide early treatment of micrometastases due to the recognition that local control has improved with aggressive combined therapy, but distant failure due to metastatic disease has increased.

97The potential toxic effects of chemotherapy include mucositis, nausea, vomiting, and bone marrow suppression.

The principal agents that have been studied alone or in combination in head and neck cancer are methotrexate, bleomycin, Taxol and derivatives, platinum derivatives (cisplatin and carboplatin), and 5-fluorouracil. The initial tumor response to chemotherapy prior to radiotherapy may predict tumor responsiveness to radiation.

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SurgerySurgery may fail due to

incomplete excision, tumor seeding in the wound, unrecognized

lymphatic or hematogenous spread,

neural invasion, or perineural spread.

Surgery also may be used in palliative cases to

reduce the bulk of the tumor and to promote

drainage from a blocked cavity (eg, antrum).

Surgery is indicated

for tumors involving bone

when the side effects of

surgery are expected to be

less

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Surgery is needed when bone is involved, and radiotherapy alone cannot be considered adequate to produce a cure. In some cases with

minimal bone involvement of the alveolar crest, a partial mandibulectomy may allow the continuity of the mandible to be maintained.

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Radiation Therapy

Radiation therapy may be administered with

intent to cure, as part of a combined radiation-

surgery and/or chemotherapy

management, or for palliation.

Radical radiotherapy is

intended to cure, the total dose is high, the course of

therapy is prolonged, and early and late

radiation effects are common.

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Radiation kills cells by interaction with water molecules in the cells, producing charged molecules that interact with biochemical processes in the cells and by causing direct damage to DNA.

The affected cells may die or remain incapable of division.

Due to a greater potential for cell repair in normal tissue than in malignant cells and a greater susceptibility to radiation due to the higher growth fraction of cancer cells, a differential effect is achieved.

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SCCs are usually radiosensitive, and early lesions are highly curable.

In general, the more differentiated the tumor, the less rapid will be the response to radiotherapy. Exophytic and well-oxygenated tumors are more radiosensitive, whereas large invasive tumors with small growth fractions are less responsive. SCC that is limited to the mucosa is highly curable with radiotherapy; however, tumor spread to bone reduces the probability of cure with radiation alone.

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Brachytherapy

Interstitial and intracavitary implants may be used to treat primary cancers in the head and neck.

Brachytherapy may be the primary treatment modality for localized tumors in the anterior two-thirds of the oral cavity, for boosted doses of radiation to a specific site, or for treatment following recurrence.

The isotopes used include cesium, iridium, and gold.

Directly implanted sources may be used to deliver radiation, or an afterloading technique may be used in which the radiation source is placed by using previously inserted catheters or guide tubes.

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COMPLICATION OF TREATMENT

Radiation Therapy–Related Mucositis and Fungal and Viral Colonization

Hyposalivation

CandidiasisCaries

Soft Tissue necrosis and Osteonecrosis

Taste and Smell Impairment

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Prevention

Prevention has focused on to tobacco as a major cause of oral cancers, and attention has been paid to strategies of tobacco cessation.

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Prognosis

The most important factor in survival is the stage of disease at diagnosis. Unfortunately, the majority of oral cancers are diagnosed in advanced stages, after becoming symptomatic. The incidence of spread is influenced by tumor size. The managing of complications of cancer treatment in itself is a challenge and also effects the prognosis.

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Conclusion

• The global increase in frequency and mortality, as well as the poor prognosis of head and neck squamous cell carcinoma, has intensified current research efforts in the field of prevention and early detection of this disease.

• The study of the carcinogenic process of the head and neck, including continued analysis of new genetic alterations, along with their temporal sequencing during initiation, promotion and progression, will allow us to identify new diagnostic and prognostic factors, which will provide a promising basis for the application of more rational and efficient treatments.

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References

Indian Journal of Cancer; April–June 2006:Volume 43, issue 2.

Scully et al, American Journal of Dentistry, Vol. 21, No. 4, August, 2008 .


Scully et al , American Journal of Dentistry, Vol. 21, No. 4, August, 2008 .

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Scully C, Cawson R. Potentially malignant oral lesions. J Epidemiol Biostat 1996;1:3-12 .

Scully C. Oral squamous cell carcinoma; From a hypothesis about a virus, to concern about possible sexual transmission. Oral Oncol 2002;38:227-34.

Molecular profiling of head and neck tumors, C. Sotiriou et al: Current Opinion in Oncology 2004, 16:211–214


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Health & Medicine

Oral cancer seminar