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Head and Neck Tumors

Head and Neck Tumors

Overview

Annually, approximately 50,000 individuals are diagnosed with head and neck cancer in the United States, and over 11,000 die of the disease. Most patients with head and neck cancer have metastatic disease at the time of diagnosis (regional nodal involvement in 43% and distant metastasis in 10%).

Head and neck cancers encompass a diverse group of uncommon tumors that frequently are aggressive in their biologic behavior. Moreover, patients with a history of head and neck cancer have the potential to develop a second primary tumor, generally secondary to the habitual use of tobacco.

These tumors occur at an annual rate of 3% to 7%, and 50% to 75% of such new cancers occur in the upper aerodigestive tract or lungs. The incidence of tobacco-related head and neck cancer is decreasing. However, the incidence of cancer due to the human papillomavirus (HPV) continues to increase at a rate of 2% to 4% per year.

The anatomy of the head and neck is complex and is divided into sites and subsites (Figure 1). Tumors of each site have a unique epidemiology, anatomy, and natural history, and require different therapeutic approaches. This chapter will review these lesions as a group and then individually by anatomic site.

Epidemiology

Gender

Head and neck cancer is more common in men, with 66% to 95% of cases by site occurring in men. The incidence by gender varies with anatomic location and has been changing as the number of female smokers has increased. The male-female ratio is currently 3:1 for oral cavity and pharyngeal cancers. Men currently are three times as likely to develop HPV-associated head and neck cancer; this imbalance in epidemiology is expected to become more pronounced in the next 20 years. In patients with Plummer-Vinson syndrome, the ratio is reversed, with 80% of head and neck cancers occurring in women.


FIGURE 1: Anatomic sites and subsites of the head and neck. The approximate distribution of head and neck cancer is oral cavity, 44%; larynx, 31%; and pharynx, 25%.

Age

The incidence of head and neck cancer increases with age, especially after 50 years of age. Although most patients are between 50 and 70 years old, younger patients can develop head and neck cancer. There are more women and fewer smokers in the younger patient group with oral cavity cancers and no known risk factors. Patients with HPV-associated head and neck cancer tend to be younger, and may be in their 30s or 40s when diagnosed with this disease. It is controversial whether head and neck cancer is more aggressive in younger patients or in older individuals. This "aggressiveness" probably reflects the common delay in diagnosis in the younger population, since, in most studies, younger patients do not have a worse prognosis than their stage-matched older counterparts.

Race

The incidence of laryngeal cancer is higher in African Americans relative to the white, Asian, and Hispanic populations.

In addition, in African Americans, head and neck cancer is associated with lower survival for similar tumor stages. The overall 5-year survival rate is 56% in whites and 34% in African Americans.

Geography

There are wide variations in the incidence of head and neck cancer among different geographic regions. The risk of laryngeal cancer, for example, is two to six times higher in Bombay, India, than in Scandinavia. The higher incidence of the disease in Asia is thought to reflect the prevalence of risk factors, such as betel nut chewing and use of smokeless tobacco (snuff). In the United States, the high incidence among urban males is thought to reflect exposure to tobacco and alcohol. Among rural women, there is an increased risk of oral cancer related to the use of smokeless tobacco.

Nasopharyngeal carcinoma is another head and neck tumor with a distinct ethnic predilection. Endemic areas include southern China, northern Africa, and regions of the far Northern Hemisphere—areas in which the diet of inhabitants includes large quantities of salted meat and fish. When people from these regions migrate to areas with a lower disease incidence, their risk falls but remains elevated. Cancer of the nasopharynx in these geographic areas also has been associated with Epstein-Barr virus (EBV) infection (see section on "Etiology and risk factors").

Etiology and Risk Factors

Risk factors for head and neck cancer include tobacco and alcohol use, ultraviolet (UV) light exposure, viral infection with EBV or HPV, and environmental exposures.

Tobacco

The incidence of head and neck tumors correlates most closely with the use of tobacco. Smoking increases the risk of death by 1% per pack-year. Smoking during treatment with radiation increases the risk of death two-fold.

Cigarettes

Head and neck tumors occur six times more often among cigarette smokers than nonsmokers. The age-standardized risk of mortality from laryngeal cancer appears to rise linearly with increasing cigarette smoking. For the heaviest smokers, death from laryngeal cancer is 20 times more likely than for nonsmokers. Furthermore, active smoking by head and neck cancer patients is associated with significant increases in the annual rate of second primary tumor development (compared with former smokers or those who have never smoked). In the Radiation Therapy Oncology Group (RTOG) 90-03 study, the risk of death doubled (hazard ratio [HR] = 2.19; 95% confidence interval [CI] 1.46–3.28) among those who smoked during radiotherapy, after accounting for pack-years and other factors, and risk of second primary tumors increased by 1.5% per pack-year (HR = 1.015; 95% CI, 1.005–1.026). Use of unfiltered cigarettes or dark, air-cured tobacco is associated with further increases in risk.

Cigars

Often misperceived as posing a lower health risk than cigarette smoking, cigar smoking results in a change in the site distribution for aerodigestive tract cancer, according to epidemiologic data. Although the incidence of cancer at some sites traditionally associated with cigarette smoking (eg, larynx, lungs) is decreased in cigar smokers, the incidence of cancer is actually higher at other sites where pooling of saliva and associated carcinogens tends to occur (oropharynx, esophagus).

Smokeless tobacco

Use of smokeless tobacco also is associated with an increased incidence of head and neck cancer, especially in the oral cavity. Smokeless tobacco users frequently develop premalignant lesions, such as oral leukoplakia, at the site where the tobacco quid rests against the mucosa. Over time, these lesions may progress to invasive carcinomas. The use of snuff has been associated with an increase in cancers of the gum and oral mucosa.

Alcohol

Alcohol consumption, by itself, is a risk factor for the development of pharyngeal and laryngeal tumors, although it is a less potent carcinogen than tobacco. For individuals who use both tobacco and alcohol, these risk factors appear to be synergistic and result in a multiplicative increase in risk.

UV Light Exposure

Exposure to UV light is a risk factor for development of cancer of the lips. At least 33% of patients with lip cancer have outdoor occupations.

Occupational Exposures

A small group of head and neck cancers may be attributable to occupational exposures. Nasal cancer has been associated with wood dust exposure, and squamous cell cancer of the maxillary sinus has been linked to nickel exposure. Petroleum exposure may be associated with pharyngeal cancer, but the relationship has not been proven.

Radiation Exposure

Exposure to radiation is clearly an important risk factor for thyroid cancer and has been associated with cancer of the salivary glands.

Viruses


FIGURE 2: Levels of the neck as determined by lymphatic drainage patterns.

TABLE 1: Lymphatic drainage of the head and neck and associated sites of primary tumors

There is a strong link between EBV exposure and the development of nasopharyngeal cancer. The etiologic role of HPV in oropharyngeal cancer is supported by a growing body of evidence. A case-control study of 100 patients with squamous cancer of the oropharynx documented that HPV DNA type 16 was found in 72% of tumor specimens. Further, 64% of the patients had antibodies to HPV-16 oncoproteins. Oral infection with HPV increased the risk of oropharyngeal cancer with an odds ratio of 14.6 (95% CI, 6.3–36.6). This risk was independent of tobacco and alcohol use. These patients appear to have a better outcome following surgery, radiotherapy, and chemotherapy. In addition, these patients have a lower incidence of second cancers and a lower risk of death from other tobacco-related illnesses (eg, heart and lung disease). The development of oropharyngeal cancer was associated with high-risk sexual behaviors, including a higher lifetime number of sexual partners, engagement in oral sex, casual sexual relations, young age at first intercourse, and infrequent condom use. It is hoped than an HPV vaccine will reduce the incidence of oropharyngeal cancer.

Diet

Epidemiologic studies suggest that dietary intake of vitamin A, β-carotene, and α-tocopherol may reduce the risk of developing head and neck cancer.

Marijuana

Smoking marijuana has been associated with development of head and neck cancer, but the degree of risk is unknown.

Anatomy

The anatomy of the head and neck region is complex. The anatomic sites are illustrated in Figure 1. More detailed descriptions are included below in the discussions of specific sites and subsites.

Levels of the Neck

The anatomy of the neck is relevant to the treatment of all head and neck cancers. The neck may be divided into levels (Figure 2). The lymphatic drainage of the unmanipulated neck is systematic and predictable; knowledge of these drainage patterns assists the clinician in locating the primary tumor that has given rise to a neck metastasis (Table 1).

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