Oral cancer

More than 90% of malignant neoplasms in the mouth are squamous cell
carcinomas arising from mucosal epithelium. Most of the remainder
arises in minor salivary glands and a few are metastases. The term oral
cancer is therefore used loosely to mean oral squamous carcinoma.

EPIDEMIOLOGY

Oral carcinoma accounts for only approximately 2% of all malignant

tumours in such countries as the United Kingdom and the United States.
In most countries where reliable data are available, the incidence of
cancer of the mouth, although variable, is low. India, Pakistan,
Bangladesh and Sri Lanka are, however, exceptional, and cancer of the
mouth accounts for approximately 40% or more of all cancer there,
although the incidence varies widely in different parts of this
subcontinent. Relatively high rates are found in parts of China, Southeast
Asia, France, Brazil and Eastern Europe.

The general feature of oral cancer is as follows:

Cancer of the mouth: key features

• Accounts for approximately 2% of all cancers in the UK

• One of the most common cancers in the Indian subcontinent

• Males more frequently affected

• Most patients are older than 40 years and incidence rises with age

• Tongue, posterolaterally, is the most common site within the mouth

• Some arise in pre-existing white or red lesions

• Tobacco and alcohol are the main causes

• In the Indian subcontinent and Southeast Asia, betel quid is the main
cause

Age and gender incidence

Oral cancer is an age-related disease, and 95% of patients are older than
40 years, with median age at diagnosis of just older than 60 years. This
may reflect time for the accumulation of genetic changes and duration of
exposure to initiators and promoters. These include chemical and physical
irritants, viruses, and hormonal effects. In addition, decreased
immunologic surveillance over time may be another explanation to the
age relation, such as seen in individuals following solid organ and
hematopoietic stem cell transplantations, individuals treated with
chemotherapy, and HIV-infected individuals

Etiology and risk factors:

Possible aetiological factors for oral cancer

• Major factors

• Tobacco smoking

• Smokeless tobacco

• Betel quid habit

• Alcohol

• Sunlight (lip only)

• Low risk factors

• Diet

• Candidosis

• Human papillomavirus*

• Lichen planus

Rare cause, but significant

• Oral submucous fibrosis

• Dyskeratosis congenita

• Fanconi’s anaemia

• Syphilis

Speculative factors
• Radiation

• Immunodeficiency

Tobacco and Alcohol

Tobacco products and alcohol are acknowledged risk factors for oral
cancer. Tobacco contains potent carcinogens, including nitrosamines,
polycyclic aromatic hydrocarbons, nitrosodiethanolamine, nitrosoproline,
and polonium. Tobacco smoke contains carbon monoxide, thiocyanate,
hydrogen cyanide, nicotine, and metabolites of these constituents.
Nicotine is a powerful and addicting drug. Epidemiologic studies have
reported that up to 80% of oral cancer patients were smokers

All forms of alcohol, including “hard” liquor, wine, and beer, have been
implicated in the etiology of oral cancer. In some studies, beer and wine
are associated with greater risk than hard liquor

The combined effects of tobacco and alcohol result in a synergistic effect

on the development of oral cancer. The mechanisms by which alcohol
and tobacco act synergistically may include dehydrating effects of
alcohol on the mucosa, increasing mucosal permeability, and the effects
of potential carcinogens in alcohol or tobacco.

Infections and immunosuppression

Human papillomavirus (HPV) types 16 and 18 are now well-established

causes of tonsil and oropharyngeal carcinomas, but their role in oral
carcinomas is poorly understood and the subject of considerable research

Immunosuppression is not a significant factor for intraoral carcinoma;

incidence is not increased in HIV infection. However, lip carcinoma is
more frequent in the immunosuppressed

Diet and malnutrition

Oral carcinoma is more frequent in those with low intake of fruit and
vegetables. Vitamin A, C and carotenoids and other antioxidants are key
protective factors, together with zinc and selenium.
Genetic predisposition

-Dyskeratosis congenita is rare, has oral precursor lesions and a

distinctive presentation, so diagnosis is usually straightforward and
established before any oral carcinoma develops.

-Fanconi anaemia is an important but rare cause of oral carcinoma in the

young, and oral carcinoma may be the presenting feature

Other Risk Factors

There is no evidence that denture use, denture irritation, irregular teeth or

restorations, and chronic cheek-biting habits are related to oral cancer
risk. However, the role of local trauma in the development of oral cancer
remains controversial. It is possible that chronic trauma, in the presence
of other risk factors and carcinogens, may promote the transformation of
epithelial cells, as has been demonstrated in animal studies.

In lip cancer, sun exposure, fair skin and a tendency to burn, pipe
smoking, and alcohol are identified risk factors.

Pathogenesis

Carcinogenesis is a genetic process that leads to a change in molecular

function, cell morphology, and ultimately in cellular behavior. This
process is not limited to the epithelium but involves a complex epithelial,
connective tissue, and immune function interaction.

Major genes involved in oral cancer include oncogenes and tumor

suppressor genes (TSGs). Regulatory genetic molecules may be involved
as well

ORAL CANCER DISTRIBUTION

Overall, the tongue is the most frequently affected site in the mouth and
the majority of cancers are concentrated in the lower part of the mouth,
particularly the lateral borders and ventral tongue, the adjacent floor of
the mouth and lingual aspect of the alveolus and retromolar region,
forming a U-shaped area extending back toward the oropharynx
Oral cancer: clinicopathological features and behavior

• Early cancers appear as white or red patches or shallow ulcers and are
painless or only slightly sore

• Later carcinomas appear as ulcers with prominent rolled edges and

induration and become painful

• More than 70% of oral cancers form on the lateral borders of the tongue
and adjacent alveolar ridge and floor of mouth

• Over 95% are well- or moderately well-differentiated squamous cell

carcinomas

• Spread is by direct invasion of surrounding tissues and by lymphatic

metastasis

• The submandibular and jugulodigastric nodes are most frequently

involved

• The prognosis deteriorates sharply with local spread and nodal

involvement

Diagnosis and Histopathology

The diagnosis is primarily based on histopathology. Within the epithelial

tumors, SCC is the most prevalent oral malignancy. It has several
subtypes based on histopathology

Staging of Oral Cancer—TNM System

The American Joint Committee on Cancer (AJCC) has developed Tumor-

Nodes-Metastasis (TNM) staging system of cancer, which reflects the
prognosis, and is therefore determinants for the treatment strategy. T is
the size of the primary tumor, N indicates the presence of regional
lymphnodes, and M indicates distant metastasis. The staging system for
OSCC combines the T, N, and M to classify lesions as stages 1 through 4.
Diagnostic Aids

Early detection of potentially malignant and malignant lesions is a

continuing goal. Patient history, thorough head and neck and intraoral
examinations, is a prerequisite. The definitive test for diagnosis remains
tissue biopsy. Such diagnostic aids include the following:

Tolonium chloride (toluidine blue) rinsing

Tolonium chloride is a dye that binds to nucleic acids and can be used as
an oral rinse in the hope of staining carcinoma and dysplastic lesions
blue. The technique is not an accurate test for either carcinoma or
premalignancy and is no more than an adjunct to clinical diagnosis.

Brush biopsy

This technique is relatively non-invasive and therefore attractive for

screening or long-term follow-up. It uses a round stiff-bristle brush to
collect cells from the surface and subsurface layers of a lesion by
vigorous abrasion. The brush is rotated in the fingers in one spot until
bleeding starts, to ensure a sufficiently deep sample. There is little or no
pain, minimal bleeding and no need for sutures. The cells collected are
transferred to a microscope slide and the smear is scanned to identify
abnormal cells.

Visualization Adjunctive Tools

Chemiluminescent devices generate light based on chemicalreactions.

The suspected area of mucosa appears brighter.Other products generate
fluorescent light using a LED source, sometimes combined with optical
filtration of a viewfinder, to enhance natural tissue fluorescence. When
using the fluorescence light, the suspected area shows loss of
fluorescence, which appears dark.

These products are promoted to assist the practitioner in discovering

mucosal abnormalities, specifically oral potentially malignant disorders
and evaluate margins of resection site.
Saliva tests

It is an attractive possibility that oral cancer or potential malignancy

might be diagnosed by a simple saliva test. More than 100 different
salivary biomarkers have been investigated. Despite claims for high
sensitivity, none has yet been proven in a well-designed trial including
patients with the many inflammatory and benign conditions with which
cancers can be confused.

Imaging

Routine radiology, computed tomography (CT), nuclear scintiscanning,

magnetic resonance imaging, and ultrasonography can provide evidence
of bone involvement or can indicate the extent of some soft tissue lesions.
The selection of the appropriate imaging modality is dependent on the
type and location of the suspected tumor

Treatment

The principal objective of treatment is to cure the patient of cancer. The

choice of treatment depends on cell type and degree of differentiation, the
site and size of the primary lesion, lymph node status, the presence of
local bone involvement, the ability to achieve adequate surgical margins,
and the presence or absence of metastases. Treatment decisions are also
impacted by appraisal of the ability to preserve oropharyngeal function,
including speech, swallowing, and esthetics, as well as the medical and
mental status of the patient.

Surgery and radiation are used with curative intent in the treatment of oral
cancer. Chemotherapy and targeted therapy are used together with the
principal therapeutic modalities of radiation and surgery and is now
considered the benchmark for management of advanced disease.

Prognosis

The most important predictors for survival of oral cancer are the
presence of HPV and stage of disease at diagnosis. Unfortunately, the
majority of oral cancers continue to be diagnosed in advanced stages,
after becoming symptomatic. Cancers positive for HPV, particularly type
16, have a better prognosis compared to HPV-negative tumors. This fact
is now used to stratify the patient’s risk; however, HPV testing must not
be considered in isolation, as other causative factors, such as tobacco
exposure may influence the staging.

Additional prognostic indicators for oral cancer include the depth of

penetration, perineural invasion, differentiation level, lymphocytic
infiltrate at interface, status of surgical margins.

Prevention

Primary prevention has focused on tobacco as a major cause of upper

aerodigestive tract cancers, and attention has been paid to strategies for
tobacco cessation. Diet has been studied in developing countries with
evidence supporting fresh fruits and vegetables, but this has not been
evident in the developed world. Likewise vitamin supplements have not
been shown effective.

ROLE OF THE DENTIST

Early diagnosis is critical. Small carcinomas are more easily excised, less
likely to have metastasised and have the best prognosis. Unfortunately,
healthcare workers, including dentists, frequently either fail to make the
diagnosis or actively delay referral

Role of the dental practitioner in cancer prevention and diagnosis

A.Prevention

• Actively discourage smoking and betel quid use

• Encourage moderation of alcohol intake

• Health promotion and education on oral carcinoma

• Provide check-ups for the edentulous and/or institutionalised elderly and

other high-risk non-attenders

B. Early diagnosis

• Be vigilant and suspicious

• Always examine all of the mucosa and the teeth

• Monitor low-risk premalignant lesions

• Refer all high-risk lesions on discovery

• Perform biopsy appropriately

C. After treatment

• Manage simple denture problems after surgery

• Alleviate the effects of post-irradiation dry mouth, e.g. preventing caries

• Monitor for recurrence, new premalignant lesions and second primary

tumours

• Monitor for cervical metastasis

• Maintain morale of and provide additional support to patients and their

relatives