Early Diagnosis Oral Cancer

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    Oral squamous cell carcinoma is a major health problem inIndia amongst all the malignancies its incidence ranks numberone in males and three in females

    Many oral cancers are detected only when they are welladvanced as a result of illiteracy or socioeconomic status ofpatient and being painless in the early stages resulting in highermorbidity and mortality

    In developing countries such as India, where there is a highprevalence of disease, the focus is on downstaging oral cancerat diagnosis from advanced to earlier disease

    INTRODUCTION

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    Oral cancer is emerging as a global burden due to increasedno. of deaths world wide

    ORAL CANCER A GLOBAL BURDEN

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    Early detection of oral premalignant lesions and conditionsimproves the prognosis and helps in better screening which savemillions of life.

    Early detection has the potential to significantly reduce oralcancer deaths and morbidity

    Early detection aims to screen the cancer at very early stagee.g. a premalignant condition or lesion

    These lesions often present as a white patch or, lessfrequently, a red patch. Progression from premalignantlesions to cancer usually occurs over years

    INTRODUCTION

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    The first step in screening for oral cancer is the completionof a patient history, which should include review of:

    General health history including a list of current medicationsand medication allergies Oral habits and lifestyle, with particular reference toquantity, frequency and duration of tobacco use and alcoholconsumption

    Symptoms of oral pain or discomfort.

    FIRST STEP

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    For early detection of oral cancer the various techiniquesemployed are:

    Vital staining by toluidine blue

    Chemilumniscence

    AutofluoroscenceCytologic (Papanicolaou) smear

    Fine needle aspiration cytology

    Brush biopsy

    Cytogenetic analysis

    Polymerase Chain reaction

    DNA sequencing methods

    Tumour markers.65,78,91

    VARIOUS TECHNIQUES

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    Toluidine blue is a acidophilic metachromatic dye belonging tothe thiazine group that selectively stains the acidic tissuecomponents

    Dye is taken up by the nuclear debris on the surface oftumour cells.

    In addition, malignant epithelium may contain intracellularcanals that are wider than normal epithelium; this is a factor

    that would enhance penetration of the dye upto depth of 50m.Toluidine Blue in dysplastic lesions and carcinomas shows

    increase uptake due to the high density of nuclear material, theloss of cell cohesion, increased mitoses and loss ofheterozygosity

    TOLUIDINE BLUE

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    The term Chemiluminescence refers to the emission of lightfrom a chemical reaction.

    The blue white light is absorbed by the cells of the normal

    mucosa and is reflected by cells with abnormal nuclei includingdysplastic and neoplastic cells.

    CHEMILUMINESCENCE

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    The acetic acid rinse putatively removes debris and disruptsthe glycoprotein barrier on the surface of the epitheliumallowing penetration.3

    The normal mucosa appears blue, whereas abnormal mucosal

    areas reflect the light (due to higher nuclear/cytoplasmic ratioof epithelial cells) and appear more aceto white with brighter,sharper and more distinct margins17

    CHEMILUMINESCENCE

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    The autoflorescence signal is finally visualized directly by ahuman observer.

    With regards to the oral cavity, normal oral mucosa emits apale green autofluorescence when viewed through theinstrument handpiece whilst abnormal tissue exhibits decreasedautofluorescence and appears darker with respect to thesurrounding healthy tissue.

    VELSCOPE

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    The concept behind tissue autoflorescence is that changes inthe structure (e.g., hyperkeratosis, hyperchromatin andincreased cellular/nuclear pleomorphism) and metabolism (e.g.

    concentration of flavin adenine dinucleotide [FAD] andnicotinamide adenine dinucleotide [NADH]) of the epithelium, aswell as changes of the subepithelial stroma (e.g. composition ofcollagen matrix and elastin), alter their interaction with light.

    These epithelial and stromal changes can alter the distributionof tissue fluorophores and as a consequence the way they emitfluorescence after stimulation with intense blue excitation (400to 460 nm) light, a process defined autoflorescence.

    VELSCOPE

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    Exfoliative cytology is a technique used for observing themicroscopic morphology of individual cells after they have beenobtained from a tissue, spread on a slide, fixed and stained.

    The usefulness of cytology is augemented in 90% of oralcancers because most of them are epithelial in origin andthereby surface lesions.

    Thus, direct sampling allows for accurate diagnosis.

    CYTOLOGICAL SMEAR

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    Fine neddle asiration cytology is a highly acceptable andrecommended technique for differentiating benign frommalignant lesions involving the lymph nodes.

    Use of this minimally invasive technique accelerates thediagnosis, treatment and overall management

    It is a safe, quick reliable procedure that can immediately

    differentiate inflammatory , reactive, cystic and neoplasticlesions.

    The armamenterium involves the use of 22 Gauze needle.

    FINE NEEDLE

    ASPIRATION CYTOLOGY

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    The oral brush biopsy, also known as OralCDx Brush Testsystem, consists of a method of collecting a trans-epithelialsample of cells from a mucosal lesion with representation of thesuperficial, intermediate and parabasal/basal layers of theepithelium

    This test was specifically designed to investigate mucosalabnormalities that would otherwise not be subjected to biopsybecause of low-risk clinical features.

    BRUSH BIOPSY

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    A specially designed brush is the non-lacerational device usedfor epithelial cell collection and samples are eventually fixedonto a glass slide, stained with a modified Papanicolaou test andanalyzed microscopically via a computer-based imaging system.

    Results are reported as "positive" or "atypical" when cellularmorphology is highly suspicious for epithelial dysplasia orcarcinoma or when abnormal epithelial changes are of uncertaindiagnostic significance respectively

    Results are defined as negative when no abnormalities can befound

    BRUSH BIOPSY

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    The gold standard for the diagnostic test still remians thetissue biopsy and histopathological confirmation

    SCALAPEL BIOPSY

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    Tumour Exfoliated cells can be subjected to additionalanalysis. Changes occur at the molecular level before they areseen under the microscope and before clinical changes occur.

    Molecular changes in the progression to SCC include commonchanges at chromosome sites that lead to changes in RNA andsubsequent protein production. LOH and other molecularchanges, including changes at p16, p53 and cyclin D, can be

    assessed in exfoliated cells

    CYTOGENETIC ANALYSIS

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    It is of three types

    Chromosome Karyotyping

    FISH (Fluorescence In Situ Hybridization)

    CGH (Comparative Genomic Hybridization)

    CYTOGENETIC ANALYSIS

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    It is considered as an important tool for the detection ofchromosome gain or lossin many human cancers

    It involves isolation of DNA from a fresh tissue specimen or

    from a tissue in paraffin block.

    The underlying principle is allellic imbalance analysis

    All the tumour supressor genes tobecome inactive requires

    the loss of one copy on one chromosome and mutation of theother copy on other chromosome.

    POLYMERASE CHAIN REACTION

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    POLYMERASE CHAIN REACTION

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    These methods are employed for the detection of smallergenetic alterations which are common in oral squamous cellcarcinoma

    These methods are used to characterize the mutational eventslike mutation in p53 gene in oral precancer and cancer

    The method is employed by fluoroscent labeleld nucleotides

    The fastest method that is available now a days is Capillaryelectrophoresis

    DNA SEQUENCING METHODS

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    A tumour marker is a molecule or tissue based processrequiring a special assay that marks the various biochemicalmarkers in the malignant tissue.

    Biomarkers arise as a result of the changes in the malignanttissue changes from one type to another type of malignancythat distinguish it from another or changes within a tumour typethat distinguish one behaviour from other

    Tumour markers are substances, such as proteins,biochemicals (hormones) or enzymes, produced by tumour cellsor by the body in response to tumour cells.

    TUMOUR MARKERS

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    Tumour markers can be detected by various methods includingantigen-antibody based techniques (enzyme linked

    immunosorbent assay, radio-immunoassay, precipitin tests, flow-cytometry, immunohistochemistry, immunoscintigraphy),spectrophotometry, chromatographic techniques and moleculargenetic methods.

    TUMOUR MARKERS

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    The recent tumour markers which help in early detection oforal cancer are:32

    A) Sialic Acid levels

    B) Serum protein profiles

    C) Serum hyaluronan levels

    TUMOUR MARKERS FOR

    ORAL CANCER

    2424

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    Lauren L Patton Adjunctive techniques for oral cancer examination andlesion diagnosis JADA 2008;139(7):896-905.

    Stefano Fedele Diagnostic aids in the screening of oral cancer J Head &Neck Oncology 2009: 1758-3284

    Jerry E. Bouquot, Oral Precancer and Early Cancer Detection in the DentalOffice Review of New Technologies The Journal of Implant & AdvancedClinical Dentistry Vol. 2, No. 3 April 2010

    Epstein JB etal ;Analysis of oral lesion biopsies identified and evaluated byvisual examination, chemiluminescence and Toluidine blue J Oral Oncology2008;44;538-544

    BIBLIOGRAPHY

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    Farah S Camile etal A pilot case control study on efficacy of acetic acidwash and chemilumniscent illumination in the visualization of oral mucosalwhite lesions J Oral Oncology2007;43;820-24

    S Ram and C H Siar Chemiluminescence as a diagnostic aid in detection oforal cancer and potentially malignant epithelial lesions Int J Oral &Maxillofacial surgery 2005;34;521-27

    Mashberg A Tolonium rinse A Screening method for recognition ofsquamous carcinoma : Continuing study of oral cancer J AMA

    1981;245;2408-2410

    BIBLIOGRAPHY

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