Worldwide, oral cavity cancer is the sixth most common cancer type. The American Cancer Society estimates that 28,500 new cases of cancer of the oral cavity and pharynx occurred in the United States in the year 2010. Approximately 7,600 die of the disease. The mean age at diagnosis is 63 years and over 70% of patients are male. Unfortunately, the overall survival rates for oral cancer have not improved significantly in the past 20 years. Surveillance Epidemiology and End Results (SEER) data from the National Cancer Institute reveal that the overall 5-year survival rate is 61.2. Racial/ethnic disparity for oral cancer is among the most striking of all cancer types and is most evident among men. Five-year survival rates are 63.7% for white men and 38.3% for black men. Causes of the disparate survival rates likely include comorbidities, later-stage disease at presentation, differences in treatment received, and possible biologic differences in the tumor and host.

Eighty to ninety percent of oral cancers are squamous cell carcinoma. Roughly 90% of patients use tobacco in some form and 75% use alcohol. The effect is synergistic and the relative risk of developing oral cancer is increased 16-fold for individuals who use both. The risk of developing a second primary tumor is also dramatically increased in those who continue to smoke following initial treatment (37% vs. 6% risk).

Disturbing cases of oral cancer are also seen in patients without obvious risk factors. Other possible causes include prolonged minor trauma from poor dentition, a diet low in fruits and vegetables, immunosuppression, and exposure to the human papillomavirus (HPV). HPV subtypes 16 and 18 are closely linked with cervical cancer and are implicated in 15% to 20% of oral and oropharyngeal cancers. These cancers more commonly arise in the oropharynx than in the oral cavity, often involving the oral cavity by direct extension. HPV-related cancers often develop in younger patients and have a better prognosis than non-HPV tumors. Cancer of the lip is classified with oral cancer and is strongly correlated with sun exposure in fair-skinned individuals. Acquired immune deficiency syndrome (AIDS) patients, transplant recipients, and others who are immunocompromised by disease or medical therapy are at increased risk for oral cancer. The cancers that occur in these individuals are unfortunately biologically very aggressive.

Genetic changes within the oral mucosa are measurable well before the development of invasive carcinoma. Chronic exposure to carcinogens damages DNA over the mucosal field. The “field effect” of altered mucosa may be evident as far as 7 cm from an established malignancy. These alterations may activate or amplify oncogenes that promote tumor cell proliferation and inhibit or inactivate tumor suppressor genes. Tumor cells are able to escape programmed cell death and proliferate self-sufficiently. Seventy to eighty percent of oral premalignant lesions contain changes in chromosome 9p21, which encodes the
tumor suppressor genes p16 and p14^ARF. The epigenetic process of methylation of these genes is the apparent mechanism of inactivation. Mutation of the p53 tumor suppressor gene has received much attention in the literature but is probably a later event in malignant transformation. p53 mutations at the margin of resection have also been correlated with increased rate of recurrence despite histologically clear margins.

The oral cavity extends from the vermillion border of the lips to the anterior tonsillar pillar (Fig. 1). For staging purposes, the following subsites are considered part of the oral cavity: lip, oral tongue (anterior two-thirds), floor of mouth, buccal mucosa, upper and lower alveolus, hard palate, and retromolar trigone. The oral cavity has rich lymphatic supply and regional nodal metastases are typically the first site of spread. The primary lymphatic drainage basins are the perifacial, upper jugular, submandibular, and submental nodes. Sites close to the midline often drain bilaterally.

The most common symptom of oral cancer is a nonhealing ulcer in the mouth followed by persistent pain. Other common symptoms include a mass, persistent halitosis, or bleeding. Trismus, loose teeth, neck mass, and difficulty with speech or swallowing usually indicate more advanced disease. When symptoms persist longer than 3 weeks, a focused examination for oral cancer is imperative.

Oral cancer arises most commonly in the floor of mouth, followed by the lateral tongue. The distribution by site is summarized in Figure 1. Diagnosis is usually made in the office by simple physical examination and biopsy using local anesthesia. Oral cancer is often very curable when detected at an early stage. The same is not true of later-stage disease. The ease of examination and access for biopsy make late recognition of disease particularly regrettable.

Oral cavity cancers are staged according to 7th edition (2010) American Joint Committee on Cancer (AJCC) guidelines. T1 to T3 tumors are staged only on the basis of size (Table 1). T4 tumors are subdivided into T4a and T4b according to the degree of invasion of surrounding structures and ultimate resectability. The TNM staging system does not yet include depth of invasion as a staging variable for oral cavity tumors. Many investigators have shown, however, that depth of invasion correlates directly with frequency of nodal metastasis. Most surgeons feel that a T1 tumor with a depth of invasion greater than 4 mm has a greater chance of developing nodal metastases than a T2 or T3 tumor that is very superficial.

The staging workup for oral cavity tumors includes a complete physical examination with focused mucosal examination of the upper aerodigestive tract and careful nodal examination. Careful palpation of the oral cavity is crucial in the staging workup as many of these tumors have unsuspected submucosal extension (particularly tongue cancers). Computed tomography (CT) scans of the primary site and neck may assist accurate locoregional staging. A search for distant metastases includes a chest radiograph and liver function tests at a minimum. CT scans of the chest and abdomen are indicated in patients considered to be at higher risk of distant disease. Positron emission tomography (PET) scans are not considered a routine part of the staging workup for head and neck cancer at this time. Because second primary tumors are detected in about 10% of patients, an examination under anesthesia (direct laryngoscopy, esophagoscopy) is performed prior to treatment initiation. Bronchoscopy is recommended only for patients with evidence of subglottic disease, persistent cough, or suspicious chest radiography findings.

Imaging techniques designed to detect dysplastic changes in oral mucosa may ultimately improve early detection and margin control for oral cavity cancer. Confocal microscopy, radiolabeled antibodies to tumor markers, narrow band imaging, and multiwavelength fluorescence and reflectance technology are technologies designed to detect subclinical disease in at-risk patients or to identify dysplasia at the margins of known cancers.