Oral and oropharyngeal cancers

ALSO KNOWN AS: Mouth cancer, tongue cancer, salivary gland cancer, gum cancer, throat (instead of oropharyngeal) cancer, cancers of the head and neck

RELATED CONDITIONS: Neck cancer, esophageal cancer, squamous cell carcinoma

DEFINITION: Oral cancer is a collective term encompassing cancers of the lips, mouth, tongue, gums, and salivary glands. Oral cancers mainly occur on the lips, tongue, or floor of the mouth but may also appear inside the cheeks, in the gums, or on the roof of the mouth. Oropharyngeal cancers occur in the pharyngeal cavity, or pharynx. The oropharynx, or throat, is between the soft palate and the hyoid bone. The top of the oropharynx connects with the oral cavity and, further up, with the nasopharynx. The bottom of the oropharynx connects with the supraglottic larynx and the hypopharynx. The oropharynx consists of the base of the tongue (including the pharyngoepiglottic folds and the glossoepiglottic folds), the tonsillar region, the soft palate (including the uvula), and the pharyngeal walls. Practically all oral and oropharyngeal cancers are squamous cell carcinomas (SCCs), which refer to cancers originating in squamous cells. Nonsquamous cell cancers of the head and neck include chondrosarcomas of the larynx, lymphomas of the tonsils, and salivary gland tumors such as adenocarcinomas.

Because the lymphatic system is one of the major ways that tumors spread or metastasize to other organs, knowing the location of lymph nodes in this area is crucial for understanding oral and oropharyngeal cancers. The lymph nodes that supply the head and neck run parallel to the jugular veins and can be classified into five levels—Level I, which refers to the submental and submandibular lymph nodes; Level II, which includes the upper jugular lymph nodes; Level III, which refers to the mid-jugular lymph nodes; Level IV, containing the lower jugular lymph nodes; and Level V, which refers to the lymph nodes of the posterior triangle.

Risk factors: Risk factors include cigarette smoking, chewing tobacco, excessive alcohol intake, and infection with human papillomavirus (HPV) or Epstein-Barr virus (EBV). HPV infection is linked to about 20 percent of esophageal squamous cell carcinomas. Gastroesophageal reflux disease (GERD), in which stomach acids enter the esophagus and destroy the esophageal lining, can contribute to pharyngeal cancer risk.

Etiology and the disease process: Oral and oropharyngeal cancers appear to be caused by deoxyribonucleic acid (DNA) damage in the cells in the mouth and throat. This DNA damage can occur from cigarette smoking, tobacco chewing, or excessive alcohol intake. Most oral and oropharyngeal cancers are carcinomas of the squamous cells, the flat cells that make up the mucosal epithelium, the layer of cells lining the inside of the mouth, nose, larynx, and throat. Less common are lymphomas, lymphoepitheliomas, and minor salivary gland carcinomas. A rare type of oral cancer is verrucous carcinoma, which usually does not metastasize but can penetrate deeply into nearby tissue.

Incidence: Approximately 58,000 new cases of oral and oropharyngeal cancer occur annually in the United States. The incidence is higher in men than women. Persons over fifty are most likely to be affected, and the median age at diagnosis occurs in the early sixties. Oropharyngeal cancer is still a relatively rare type of cancer, and death rates due to oral and oropharyngeal cancers have been decreasing since 1975.

Symptoms: Symptoms of oral and oropharyngeal cancer include lumps of white, red, or dark patches inside the mouth that do not recede with time; mouth sores that do not heal or that enlarge over time; lumps in the neck; persistent pain in the mouth or tongue; thickening of the cheek; swelling or pain in the jaw; soreness in the throat or a feeling that something is caught in the throat; difficulty swallowing; difficulty chewing or moving the tongue (late-stage symptom); difficulty moving the jaw (late-stage symptom); pain around the teeth; loosening of the teeth not associated with periodontal disease; poorly fitting dentures; numbness of the tongue or mouth; and hoarseness or changes in the voice.

Screening and diagnosis: Frequent oral examinations are the best way to detect oral and throat cancer signs. Clinical suspicion of head and neck cancer is based on the presence of any of the above symptoms for more than three weeks. When a tumor is detected, it is graded or staged to determine how benign or aggressive it is. The TNM (tumor/lymph node/metastasis) staging system is a standard way of classifying tumors. T represents the size of the primary tumor and which tissues of the oral cavity or oropharynx the tumor has spread to, if any. N refers to the extent of spread to regional lymph nodes. M denotes whether the tumor has metastasized to distant organs. The most common metastatic sites are the lungs, liver, and bones. Within each of these designations, there are several subcategories.

Following TNM staging, the tumor is classified as Stage 0, I, II, III, or IV. Stage 0 refers to a tumor confined to the outer layer of oral or oropharyngeal tissue and has not penetrated deeper or metastasized. Stage I tumors are less than two centimeters (cm) in their greatest dimension and have not metastasized. Stage II tumors are between two cm and four cm in the greatest dimension and have not metastasized. Stage III tumors are larger than four cm in diameter and have not metastasized, although they may have invaded one of the nearby lymph nodes. Stage IV is further divided into three substages—Stage IVA, in which tumors have spread to nearby sites and may or may not have invaded one or more nearby lymph nodes; Stage IVB, in which tumors may or may not have spread to nearby sites but have spread to one or more lymph nodes, and Stage IVC, in which tumors have metastasized to distant organs.

Treatment and therapy: The specific treatment varies based on the location and stage of the cancer. Primary care physicians will refer patients to specialists, including oral and maxillofacial surgeons, otolaryngologists (ear, nose, and throat doctors), medical oncologists, radiation oncologists, and plastic surgeons. Specialists often work together at specialized cancer treatment facilities to provide tailored patient care. Treatment options include radiation therapy, oral chemotherapy, surgery, and combinations of these treatments. The most commonly used treatment is a combination of radiation therapy and chemotherapy with the drug cisplatin. Sometimes, surgery is necessary to remove the cancer cells from a localized region, followed by radiation therapy to destroy any remaining cancer cells. Chemotherapy is sometimes given before other treatments to enhance the effectiveness of the follow-up treatment. In addition, treatments for symptoms and the side effects of therapies are often administered concomitantly.

Radiation therapy can take the form of external radiation from specialized equipment or internal radiation when radioactive substances are placed in seeds, needles, or plastic tubes and inserted in the tissue. The preferred method of delivery for radiation therapy, intensity-modulated radiotherapy, focuses radiation to more selectively kill the tumor instead of the surrounding healthy tissue. Surgery can be performed to remove tumors in the mouth or throat or lymph nodes in the neck.

Targeted therapies are also available for patients with advanced cancer who cannot tolerate chemoradiation. For example, Cetuximab (Erbitux), a monoclonal antibody directed at a protein abundant in cancer cells in this region, may be combined with radiation therapy and additional surgical considerations. Before starting treatment, patients should ask their physicians about the treatment length and procedure, risks, side effects, and possible results.

Prognosis, prevention, and outcomes: The prognosis is good if detected and treated early. However, many oral and throat cancers are diagnosed in the late stage, often because they are painless at early stages or cause minor pains similar to a toothache. The stage of cancer also determines the treatment type. After treatment, the cancer may reappear (recur or relapse). The recurrence can occur in the mouth or throat (local recurrence), lymph nodes (regional relapse), or a distant site in the body, often the lungs (distant recurrence). A relapse is associated with a poorer prognosis. The five-year relative survival rate is a statistic that calculates the survival of cancer patients relative to the expected survival for people without cancer. This statistic can be used as a guide, but other factors, such as age, health, and tumor properties, must be considered before arriving at a complete prognosis. The five-year relative survival rate for oral cavity cancer varies by location, but generally, it is between 75 and 90 percent. Oropharynx cancer has the worst prognosis, with five-year survival rates of around 60 percent for localized cases and 29 percent for distant spreads. Conversely, lip cancer has the best survival rates, with 94 percent of individuals with localized tumors surviving five years and 38 percent in those whose cancer has a distant spread.

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