Nature Of This Cancer Type

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The larynx, commonly known as the voice box or Adam's apple, is above the trachea and below the pharynx (Figures 7.1 and 8.1). It includes three anatomic subsites: the glottis, including the vocal fold or vocal cords, depicted near the middle of Figure 8.1; the supraglottis, which encompasses all tissues above the vocal folds and below the pharynx and includes the epiglottis, a fold that closes the larynx during swallowing to prevent food inhalation; and the subglottis, or area below the vocal fold.

The American Cancer Society (Jemal et al. 2006) has estimated that about 9,510 new cases of and 3,740 deaths from cancer of the larynx (ICD-9 161; ICD-O C32.0-C32.9) will occur in 2006. Laryngeal cancer ranks 16th in incidence and mortality among men in the United States, and 28th and 25th in incidence and mortality, respectively, among women. Both incidence and mortality are more than 4 times higher in men than women and are higher among blacks than whites, especially in men. The risk of developing laryngeal cancer increases with age. However, the incidence of laryngeal cancer, adjusted for age, has decreased by an average of 2.6% per year since 1988.

Most cancers of the larynx are squamous-cell carcinomas that arise from the thin, flat cells (squamous cells) that line the upper airway. Those tumors, like squamous-cell carcinomas of the oral cavity and pharynx, develop gradually as normal cells develop into clones of progressively abnormal cells. As the clones accumulate genetic damage, some may undergo malignant transformation, first into carcinoma in situ, and later into inva-

FIGURE 8.1 Larynx viewed from behind.

SOURCE: Modified from Grey's Anatomy of the Human Body. Available at http://

FIGURE 8.1 Larynx viewed from behind.

SOURCE: Modified from Grey's Anatomy of the Human Body. Available at http://

sive cancer. Premalignant lesions often regress after the discontinuation of tobacco use and alcohol consumption.

The most important risk factors for laryngeal cancer are tobacco-smoking (all forms) (IARC 2004) and heavy consumption of alcohol, especially when drinking and smoking occur in combination (IARC 1988). Cancer of the larynx is rare in lifelong nonsmokers, even though nonsmoking drinkers have been reported to have increased risk (Burch et al. 1981, Elwood et al. 1984). Risk increases with the number of cigarettes smoked per day and duration of smoking. The independent effect of tobacco on laryngeal cancer is greater than that of alcohol consumption. The effects of occupation on the risk of laryngeal cancer have been difficult to study, because of the powerful relationship of this cancer with tobacco use and alcohol consumption, and the little information on alcohol consumption and tobacco use in many occupational studies. Exposure to strong sulfuric acid mist is an established cause of laryngeal cancer (IARC 1987). Other factors that may increase risk, but on which current data are limited, include exposure to mustard gas (HHS 2004), steam and fumes from isopro-pyl alcohol (IARC 1987), metalworking fluids (Eisen et al. 1994, Zeka et al. 2004), and chronic infection with human papilloma virus (Rees et al. 2004).

The combination of tobacco-smoking and heavy drinking causes a much larger increase in laryngeal cancer risk than would be expected from the sum of the relative risk (RR) estimates associated with the separate exposures. For example, a study of laryngeal cancer published in 1976 (Wynder and Hoffmann 1976) found that, compared with men who neither smoked nor drank, those who reported both smoking (35 or more cigarettes per day) and drinking (seven or more alcoholic drinks per day) had an RR of 22.1 (95% confidence interval [CI] 7.8-62.1). Smoking alone was associated with an RR of 7.0 (95% CI 2.5-19.4), whereas the RR of this level of alcohol consumption alone could not be calculated because of the absence of cases. That study, conducted during the period when many studied occupational populations were experiencing exposure to asbestos, illustrates the strength of the association of laryngeal cancer with smoking and drinking.

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