Malignant oral lesions--particularly in their early stages--can resemble benign conditions. In this 2-part series, I will offer practical advice on how to identify symptomatic lesions. Here I focus on oral cancer and lichen planus. In a future article, I will discuss viral infections, candidiasis, benign mucous membrane pemphigoid, and erythema multiforme.

Oral squamous cell carcinoma accounts for about 3% of all cancers in the United States. Risk increases with age, although recent years have seen a trend toward increasing prevalence in younger men. Oral squamous cell carcinoma affects more men than women, and risk varies according to country and race. In the United States, the incidence is about 12.3% in blacks, 10% in whites, 5.7% in Hispanics, and 6% in Asians. Mortality is about 4.8% in blacks, 2.5% in whites, 2.3% in Asians, and 1.3% in Hispanics.¹ The overall 5-year survival rate is about 50%. This relatively low rate is largely attributable to delayed diagnosis of an initially innocuous-appearing, asymptomatic lesion in a location difficult for the patient and clinician to observe readily.¹

Risk factors for oral malignancy. These include heavy cigarette smoking and the use of smokeless tobacco; alcohol intake (especially when coupled with tobacco use); low serum levels of b-carotene; radiation therapy; iron deficiency; infection with oncogenic viruses, including human papillomavirus (HPV) and herpes simplex virus (HSV); immunosuppression; and the activity of proto-oncogenes, tumor suppressor genes, and gatekeeper molecules in association with alcohol and tobacco use.² The mechanisms and interactions involved in malignant transformation are complex, but the result of the combination of environmental factors and genetics is defective carcinogen metabolism and cellular DNA repair capabilities, which lead to tumor growth.

Figure 1

Figure 2

Clinical features. The most common type of intraoral neoplasm is squamous cell carcinoma; others include oral adenocarcinoma, Kaposi sarcoma, and melanoma. The last 3 conditions do not generally involve pain. About 85% of oral carcinomas arise on the lips, tongue, oropharynx, and floor of the mouth. Rarely, squamous cell carcinoma may present on the soft palate and attached gingival tissue (Figure 1).Pain is not often the presenting feature, although patients may complain of an "irritation" or "sore." Initial signs include a change in color of the normally pink epithelium to red (erythroplakia or erythroplasia), red/white (patchy erythema), or white (leukoplakia) (Figure 2); ulceration and/or erosion; a change in surface texture (eg, stippling or corrugation); and, in advanced cases, induration of the peripheral area of the lesion, failure to heal, and neck lymphadenopathy.³

Any red and/or white lesion that presents with surface corrugation, stippling, or induration is considered dysplastic or neoplastic until proved otherwise. White plaque of any size that persists for several months may be dysplastic even if it does not display these clinical characteristics. It should be assessed by biopsy because of the risk of malignant transformation. Past or current snuff or tobacco use may predispose a user to epithelial neoplastic transformation.

Although oral squamous cell carcinoma typically presents as a single lesion, a number of reports suggest that persons with this disease are at increased risk for future oral malignancy.^4,5 In one study, 19% of patients with oral cancer observed at 1 year were found to have new primary cancers.⁶ Thus, continued thorough assessment of the mouth is warranted in patients in whom the initial presentation of squamous cell carcinoma is a solitary lesion.

Tongue malignancy typically involves the anterior two thirds of the lateral and ventral surfaces. Small lesions may be aggressive and quickly invade the musculature. Consequently, nodal metastases may occur early in the course of the disease.⁷ The importance of early detection cannot be overemphasized, given that mortality is highly correlated with metastasis. About 60% to 70% of cancer deaths related to tongue malignancy follow recurrence of tongue lesions. Only 15% of deaths are the result of distant metastases, and 20% to 40% are related to second primary cancers.^8,9

Tumors that arise on the floor of the mouth may spread to adjacent tongue and gingival tissue. Lesions in this area are aggressive, and examination may reveal submandibular and cervical nodal involvement. If these nodes are fixed to the mandible, suspect periosteal involvement, possible bone invasion, and advanced disease. Advanced squamous cell carcinoma that involves the gingiva may also cause teeth to loosen as a result of bone destruction.

Five-year survival for patients with squamous cell carcinoma depends on the site of the malignancy and the length of time the lesion has been present. If a lesion remains localized and does not invade the basement membrane, survival increases dramatically. Significant morbidity is associated with attempts to prolong survival. For tongue lesions, survival is dramatically increased if there is no nodal involvement at presentation.¹⁰

Figure 3

Differential diagnosis. Benign conditions that may resemble squamous cell carcinoma include benign hyperkeratosis, lichen planus, lichenoid drug reaction, Behçet disease, major aphthae, erythematous candidiasis, areata migrans (geographic tongue), papilloma, verruca vulgaris, and chemical or medicinal burns. Snuff keratosis, a premalignant condition, presents as a generalized whitening coupled with surface corrugation (Figure 3). A high transformation rate has been demonstrated in these lesions.

Diagnostic procedures. In addition to history, clinical presentation, and tissue biopsy, a number of procedures may be useful in assessing for oral cancer. Toluidine blue dye in a 1% aqueous solution applied over a small area with a cotton swab or a larger area via rinse is a simple tool used to assess excessive mitotic activity or mucopolysaccharide production, findings that suggest squamous cell carcinoma.¹¹

Another potentially useful procedure--exfoliative cytology--involves removal of cells with a cytology brush. This painless procedure is reported to have high sensitivity and specificity.¹² The technique is particularly useful in patients who require repeated procedures in multiple sites.¹³ Incisional biopsy remains the gold standard for evaluation of potential malignancy.