A. State of the Science

Screening and Early Detection

Screening for oral cancer should include a thorough history and physical examination. The clinician should visually inspect and palpate the head, neck, oral, and pharyngeal regions. This procedure involves digital palpation of neck node regions, bimanual palpation of the floor of mouth and tongue, and inspection with palpation and observation of the oral and pharyngeal mucosa with an adequate light source; mouth mirrors are essential to the examination. Forceful protraction of the tongue with gauze is necessary to visualize fully the posterior lateral tongue and tongue base.

The clinician should review the social, familial, and medical history and should document risk behaviors (tobacco and alcohol usage), a history of head and neck radiotherapy, familial history of head and neck cancer, and a personal history of cancer. Patients over 40 years of age should be considered at a higher risk for oral cancer. 3

Diagnosis can be delayed by several months or more if the clinician treats the patient’s complaints empirically with drugs instead of providing a thorough physical examination and workup. Patients with complaints lasting longer than 2-4 weeks should be referred promptly to an appropriate specialist to obtain a definitive diagnosis. If the specialist detects a persistent oral lesion, a biopsy should be performed without delay.

The many signs and symptoms of oral cancer are usually divided into early and late presentation. They can be so diverse that the differential diagnosis may not lead to oral malignancy. Table 1 summarizes the signs and symptoms.

Table 1: Frequent Signs and Symptoms of Oral Cancer



Persistent red and/or white patch Nonhealing ulcer

Progressive swelling or enlargement Unusual surface changes

Sudden tooth mobility without apparent


Unusual oral bleeding or epistaxis Prolonged hoarseness

Indurated area

Paresthesia, dysesthesia of the tongue

or lips

Airway obstruction

Chronic earache (chronic serous otitis


Trismus Dysphagia

Cervical lymphadenopathy Persistent pain or referred pain Altered vision

Table 2: Comparison of Toluidine Blue Uptake with Microscopic Diagnosis

Biopsy Diagnosis
No. Lesions

Because patients may be at risk for developing multiple primary tumors simultaneously or in sequence, the entire visible mucosa of the upper aerodigestive tract must be examined. In addition, lymph nodes in the head and neck area-particularly along the jugular chain-must be palpated. Approximately 90% of patients with squamous cell carcinoma in a lymph node in the neck area will have an identifiable primary tumor elsewhere, and about 10% will have cancer in the neck lymph node (4) as an isolated finding (“unknown primary”). Thus, most cancers in the neck node represent a metastasis from a primary tumor located in the head and neck region; this primary site must be identified. (5,6)

Toluidine blue (vital staining) also is a useful adjunct to clinical examination and biopsy. The mechanism is based on selective binding of the dye to dysplastic or malignant cells in the oral epithelium. It may be that toluidine blue selectively stains for acidic tissue components and thus binds more readily to DNA, which is increased in neoplastic cells.

Toluidine blue has been recommended for use as a mouthwash or for direct application on suspicious (9 ) lesions; its value comes from its simplicity, low cost, noninvasiveness, and accuracy (Table 2). In addition, it can help to determine the most appropriate biopsy sites and to surgically delineate margins. Meta-analysis of toluidine blue staining in oral cancer screening found that its sensitivity ranged from 93.5% to 97.8%, and specificity from 73.3% to 92.9%. (7)

The disadvantages of toluidine blue include the risk of obtaining a false negative reaction in a case where the patient is not followed up adequately. In contrast, the infrequent false-positive only subjects the patient to a biopsy. No in vivo observations or reports have suggested a mutagenic effect from this stain. (8)


Currently, the most effective way to control oral cancer is to combine early diagnosis and timely and appropriate treatment. Because more than 90% of all oral cancers are squamous cell carcinomas, the vast majority of oral cancers will be diagnosed from lesions on the mucosal surfaces.

The clinician’s challenge is to differentiate cancerous lesions from a multitude of other red, white, or ulcerated lesions that also occur in the oral cavity. Most oral lesions are benign, but many have an appearance that may be confused with a malignant lesion, and some previously considered benign are now classified premalignant because they have been statistically correlated with subsequent cancerous (10) changes. Conversely, some malignant lesions seen in an early stage may be mistaken for a benign (11) change. Any oral lesion that does not regress spontaneously or respond to the usual therapeutic measures should be considered potentially malignant until histologically shown to be benign. A period of 2-3 weeks is considered an appropriate period of time to evaluate the response of a lesion to therapy before obtaining a definitive diagnosis.

A definitive diagnosis requires a biopsy of the tissue. Biopsies may be obtained using surgical scalpels or biopsy punches and typically can be performed under local anesthesia. Incisional biopsy is the removal of a representative sample of the lesion; excisional biopsy is the complete removal of the lesion, with a borde