EARLY DIAGNOSIS OF

ORAL CANCER
 INTRODUCTION
Oral squamous cell carcinoma is a major health problem in
India amongst all the malignancies its incidence ranks number
one in males and three in females

Many oral cancers are detected only when they are well
advanced as a result of illiteracy or socioeconomic status of
patient and being painless in the early stages resulting in higher
morbidity and mortality

In developing countries such as India, where there is a high

prevalence of disease, the focus is on downstaging oral cancer
at diagnosis from advanced to earlier disease
 ORAL CANCER A GLOBAL BURDEN

Oral cancer is emerging as a global burden due to increased

no. of deaths world wide
 INTRODUCTION
Early detection of oral premalignant lesions and conditions
improves the prognosis and helps in better screening which save
millions of life.

Early detection has the potential to significantly reduce oral

cancer deaths and morbidity

Early detection aims to screen the cancer at very early stage

e.g. a premalignant condition or lesion

These lesions often present as a white patch or, less

frequently, a red patch. Progression from premalignant
lesions to cancer usually occurs over years
 FIRST STEP
The first step in screening for oral cancer is the completion
of a patient history, which should include review of:

General health history including a list of current medications

and medication allergies
 Oral habits and lifestyle, with particular reference to
quantity, frequency and duration of tobacco use and alcohol
consumption
 Symptoms of oral pain or discomfort.
 VARIOUS TECHNIQUES
For early detection of oral cancer the various techiniques
employed are:
Vital staining by toluidine blue
Chemilumniscence
Autofluoroscence
Cytologic (Papanicolaou) smear
Fine needle aspiration cytology
Brush biopsy
Cytogenetic analysis
Polymerase Chain reaction
DNA sequencing methods
Tumour markers.65,78,91
 TOLUIDINE BLUE
Toluidine blue is a acidophilic metachromatic dye belonging to
the thiazine group that selectively stains the acidic tissue
components

Dye is taken up by the nuclear debris on the surface of

tumour cells.

In addition, malignant epithelium may contain intracellular

canals that are wider than normal epithelium; this is a factor
that would enhance penetration of the dye upto depth of 50µm.
Toluidine Blue in dysplastic lesions and carcinomas shows
increase uptake due to the high density of nuclear material, the
loss of cell cohesion, increased mitoses and loss of
heterozygosity
 CHEMILUMINESCENCE
The term ‘Chemiluminescence’ refers to the emission of light
from a chemical reaction.

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

mucosa and is reflected by cells with abnormal nuclei including
dysplastic and neoplastic cells.
 CHEMILUMINESCENCE
The acetic acid rinse putatively removes debris and disrupts
the glycoprotein barrier on the surface of the epithelium
allowing penetration.3

The normal mucosa appears blue, whereas abnormal mucosal

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

The autoflorescence signal is finally visualized directly by a

human observer.

With regards to the oral cavity, normal oral mucosa emits a

pale green autofluorescence when viewed through the
instrument handpiece whilst abnormal tissue exhibits decreased
autofluorescence and appears darker with respect to the
surrounding healthy tissue.
 VELSCOPE

The concept behind tissue autoflorescence is that changes in

the structure (e.g., hyperkeratosis, hyperchromatin and
increased cellular/nuclear pleomorphism) and metabolism (e.g.
concentration of flavin adenine dinucleotide [FAD] and
nicotinamide adenine dinucleotide [NADH]) of the epithelium, as
well as changes of the subepithelial stroma (e.g. composition of
collagen matrix and elastin), alter their interaction with light.

These epithelial and stromal changes can alter the distribution

of tissue fluorophores and as a consequence the way they emit
fluorescence after stimulation with intense blue excitation (400
to 460 nm) light, a process defined autoflorescence.
 CYTOLOGICAL SMEAR

Exfoliative cytology is a technique used for observing the

microscopic morphology of individual cells after they have been
obtained from a tissue, spread on a slide, fixed and stained.

The usefulness of cytology is augemented in 90% of oral

cancers because most of them are epithelial in origin and
thereby surface lesions.

Thus, direct sampling allows for accurate diagnosis.

 FINE NEEDLE
ASPIRATION CYTOLOGY

Fine neddle asiration cytology is a highly acceptable and

recommended technique for differentiating benign from
malignant lesions involving the lymph nodes.

Use of this minimally invasive technique accelerates the

diagnosis, treatment and overall management

It is a safe, quick reliable procedure that can immediately

differentiate inflammatory , reactive, cystic and neoplastic
lesions.
The armamenterium involves the use of 22 Gauze needle.
 BRUSH BIOPSY
The oral brush biopsy, also known as OralCDx Brush Test
system, consists of a method of collecting a trans-epithelial
sample of cells from a mucosal lesion with representation of the
superficial, intermediate and parabasal/basal layers of the
epithelium

This test was specifically designed to investigate mucosal

abnormalities that would otherwise not be subjected to biopsy
because of low-risk clinical features.
 BRUSH BIOPSY
A specially designed brush is the non-lacerational device used
for epithelial cell collection and samples are eventually fixed
onto a glass slide, stained with a modified Papanicolaou test and
analyzed microscopically via a computer-based imaging system.

Results are reported as "positive" or "atypical" when cellular

morphology is highly suspicious for epithelial dysplasia or
carcinoma or when abnormal epithelial changes are of uncertain
diagnostic significance respectively

Results are defined as negative when no abnormalities can be

found
 SCALAPEL BIOPSY

The gold standard for the diagnostic test still remians the
tissue biopsy and histopathological confirmation
 CYTOGENETIC ANALYSIS

Tumour Exfoliated cells can be subjected to additional

analysis. Changes occur at the molecular level before they are
seen under the microscope and before clinical changes occur.

Molecular changes in the progression to SCC include common

changes at chromosome sites that lead to changes in RNA and
subsequent protein production. LOH and other molecular
changes, including changes at p16, p53 and cyclin D, can be
assessed in exfoliated cells
 CYTOGENETIC ANALYSIS

It is of three types

Chromosome Karyotyping

FISH (Fluorescence In Situ Hybridization)

CGH (Comparative Genomic Hybridization)

 POLYMERASE CHAIN REACTION

It is considered as an important tool for the detection of

chromosome 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 the
other copy on other chromosome.
POLYMERASE CHAIN REACTION
 DNA SEQUENCING METHODS
These methods are employed for the detection of smaller
genetic alterations which are common in oral squamous cell
carcinoma

These methods are used to characterize the mutational events

like 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 Capillary

electrophoresis
 TUMOUR MARKERS

A tumour marker is a molecule or tissue based process

requiring a special assay that marks the various biochemical
markers in the malignant tissue.

Biomarkers arise as a result of the changes in the malignant

tissue changes from one type to another type of malignancy
that distinguish it from another or changes within a tumour type
that distinguish one behaviour from other

Tumour markers are substances, such as proteins,

biochemicals (hormones) or enzymes, produced by tumour cells
or by the body in response to tumour cells.
 TUMOUR MARKERS

Tumour markers can be detected by various methods including

antigen-antibody based techniques (enzyme linked
immunosorbent assay, radio-immunoassay, precipitin tests, flow-
cytometry, immunohistochemistry, immunoscintigraphy),
spectrophotometry, chromatographic techniques and molecular
genetic methods.
 TUMOUR MARKERS FOR
ORAL CANCER
The recent tumour markers which help in early detection of
oral cancer are:32

A) Sialic Acid levels

B) Serum protein profiles

C) Serum hyaluronan levels

24
 BIBLIOGRAPHY
Lauren L Patton Adjunctive techniques for oral cancer examination and
lesion 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 Dental
Office – Review of New Technologies The Journal of Implant & Advanced
Clinical Dentistry Vol. 2, No. 3 • April 2010

Epstein JB etal ;Analysis of oral lesion biopsies identified and evaluated by

visual examination, chemiluminescence and Toluidine blue J Oral Oncology
2008;44;538-544
 BIBLIOGRAPHY
Farah S Camile etal A pilot case control study on efficacy of acetic acid
wash and chemilumniscent illumination in the visualization of oral mucosal
white lesions J Oral Oncology2007;43;820-24

S Ram and C H Siar Chemiluminescence as a diagnostic aid in detection of

oral cancer and potentially malignant epithelial lesions Int J Oral &
Maxillofacial surgery 2005;34;521-27

Mashberg A Tolonium rinse – A Screening method for recognition of

squamous carcinoma : Continuing study of oral cancer J AMA
1981;245;2408-2410