Essentials of Diagnosis

• Nonhealing ulcer, painful or bleeding lesion.
  
• Lump in oral cavity or oropharynx.
  
• Neck mass.
  
• Dysphagia, dysphonia, or otalgia.
  
• Weight loss.
  
• Mass on imaging in primary site or neck.
  
• Positive biopsy of lesion.

General Considerations

The oral cavity is bounded anteriorly by the vermilion border of the lip, superiorly by the hard-soft palate junction, laterally by the tonsillar pillars, and inferiorly by the circumvallate papillae of the tongue. Cancer of the oral cavity is classified by subsite: lip, oral tongue (anterior two thirds), buccal mucosa, floor of mouth, hard palate, upper and lower gingiva (alveolar ridges), and retromolar trigone. There is an estimated annual incidence of 23,110 new oral cavity cancers in the United States with approximately 5370 deaths per year. Men are affected 2–4 times more often than women for all racial and ethnic groups. The incidence of oral cancer increases with age, with median age at diagnosis of 62, although there is a trend of increasing incidence of tongue cancer among young people.

Tobacco use (both chewing and smoking), alcohol, and betel nut chewing are well-established causes of oral cavity cancer, and their carcinogenic effects are often synergistic. Other etiologic factors include poor oral hygiene and immunosuppression. The majority (90%) of cases of lip cancer are related to chronic sun exposure.

The oropharynx is posterior to the oral cavity and is bounded by the soft palate superiorly and hyoid inferiorly. Oropharyngeal subsites include the base of tongue (posterior third), palatine tonsil, soft palate, and posterior pharyngeal wall. These lesions are often silent in early stages and, consequently, frequently present at advanced stage. Cancer of the oropharynx occurs in an estimated 7570 patients in the United States each year, resulting in approximately 1340 deaths. Males are afflicted 3–5 times more frequently than females. Oropharyngeal cancer is frequently related to tobacco and alcohol use, although 30–50% of cases may be related to human papilloma virus (especially HPV-16), particularly in tonsil cancer.

Staging

Staging for both lip and oral cavity cancer is determined according to the 2010 American Joint Committee on Cancer (AJCC) TNM (tumor, node, metastasis) staging system (Table 23–1). AJCC staging for oropharyngeal cancer is shown in Table 23–2.

Pathogenesis

The oral cavity and the oropharynx are lined by squamous epithelium. Therefore, the most common cancer arising from these regions is squamous cell carcinoma (SCC). Non-SCC histologies account for less than 10% of malignant lesions of the oral cavity. Minor salivary glands found throughout the oral cavity and oropharynx can give rise to adenocarcinoma, adenoid cystic carcinoma, mucoepidermoid carcinoma, and polymorphous low-grade carcinoma. Lymphoma is the second most common tumor of the tonsillar fossa. Other malignant tumors include sarcoma and mucosal melanoma.

Cancers of the oral cavity are often heralded by precancerous lesions. Leukoplakia and erythroplakia are white and red areas, respectively, which are abnormal but not necessarily neoplastic. These lesions may be entirely benign, precancerous, or frankly invasive, although this can only be determined after biopsy with histologic evaluation. Precancerous lesions range from dysplasia to carcinoma in situ and describe abnormal-appearing cells that have not invaded normal underlying epithelial tissues. Dysplasia is classified as mild, moderate, or severe according to its tendency to progress to cancer. Dysplasia, in mild forms, can regress if the carcinogenic agent is removed. Leukoplakia is usually a benign condition that is unlikely to progress into cancer (5%). Erythroplakia is more likely to be malignant at the time of the initial biopsy (51%).

The incidence of lymph node involvement from cancers of the oral cavity is related to the depth of invasion, site, size, and histologic grade of the primary tumor. Tumors of thickness greater than 1.5–2 mm are more likely to present with nodal metastases. Cancers of the oral tongue and floor of mouth have a higher incidence of nodal metastases than do cancers of the lip, hard palate, and buccal mucosa. Cancers of the lip most commonly involve the lower lip and rarely proceed to lymphatic spread (<10%). In the case of nodal spread from lip cancer, it is typically the submental and submandibular nodes (level I) that are involved. Lateral tongue, floor of mouth, and buccal cancers drain to the ipsilateral submandibular nodal basin as well as to the upper (level II) and middle (level III) jugulodigastric nodes. Midline tumors may drain bilaterally.

Oropharyngeal tumors are frequently associated with nodal metastases at the time of diagnosis. The extensive lymphatics in this region drain primarily to the jugulodigastric basin (levels II to IV). It is important to note, however, that the retropharyngeal and parapharyngeal nodes are also at risk with oropharyngeal cancers.

Lung, liver, and bone are common metastatic sites for SCC of the oral cavity and oropharynx.

Prevention