Discussion on Laryngeal Cancer

The larynx is the organ of voice production. It is the part of the respiratory tract between the pharynx and the trachea. It consists of a framework of cartilages and elastic membranes housing the vocal folds and the muscles, which control the position and tension of these elements. The epithelium of the larynx is similar to that of the skin (i.e. stratified squamous epithelium rather than respiratory epithelium found in the rest of the upper and lower airways).


The majority of malignant neoplasms of the larynx are squamous cell carcinomas.  Squamous cell carcinomas of the larynx represent approximately two percent of all cancer deaths.  It is a disease mainly of males, with a sex ratio of 8:1.  The peak incidence of carcinoma of the larynx is the fifth and sixth decades of life.  Laryngeal carcinoma occurs more commonly in individuals with a large ethanol intake.  Over 95% of patients are smokers; 15 pack-years of smoking increase the risk 30-fold. The incidence of larynx cancer is decreasing, particularly among men, most likely due to changes in smoking habits.  Dysplasia follows the inhalation of irritants such as tobacco smoke that contains known potent carcinogens including 3,4-benzpyrene and other polycyclic aromatic hydrocarbons.  Consumption of alcohol and smoking combined has a synergistic effect in the cause of this cancer.  It is a premalignant condition from which carcinoma may develop after a period of years (usually 15 or more years from the time of exposure). An important point here is that almost all epidemiological studies assume a minimum of 15 years latency.


Evidence from epidemiological studies supports the involvement of new risk factors in the etiology of larynx cancer.   These risk factors include infectious (viral) or environmental (nutritional and occupational).  Numerous studies have suggested that certain viruses cause squamous cell carcinoma of the head and neck. The presence of human papillomavirus (HPV) antibodies when tested is significantly higher in people with laryngeal cancer versus non-laryngeal cancers.  In addition, exposure to certain chemicals such as nickel, oleum, sulfuryl chloride, sulfuric acid mist and isopropyl alcohol may increase the risk of developing this cancer.


Laryngeal cancer arises from progressive accumulation of genetic alterations that lead to selection of a clonal population of transformed cells. Head and neck cancers (including laryngeal cancer) may require more genetic alterations in their development than other solid tumors, thus explaining the often long (15- to 25-year) period of latency after initial toxin exposure. Carcinogenesis is induced by DNA damage, mutations, and adducts. Laryngeal squamous cell carcinoma may appear as a mucosal irregularity, erythroplasia, or leukoplakia.


Carcinoma may arise from the mucous membrane of any part of the larynx; however, there is a predilection for the true vocal cords, particularly the anterior portions of the true vocal cords.  The epiglottis, pyriform sinus and postcricoid area also are common sites of origin of carcinoma.  For purposes of clinical staging and end result reporting, carcinomas of the larynx can be divided into supraglottic, glottic, subglottic and hypopharyngeal lesions.  Supraglottic lesions involve the epiglottis, aryepiglottic fold and false vocal cords.  Glottic lesions are limited to the area of the true vocal cords.  Subglottic lesions include the glottic area as well as the subglottic area.  Hypopharyngeal lesions may be divided into lesions of the pyriform sinus, postcricoid area and posterior pharyngeal wall.


The early symptom of carcinoma of the true vocal cords is hoarseness.  In any patient with hoarseness lasting two weeks, laryngoscopy should be done.  Any discrete lesions of the mucous membrane of the larynx should be biopsied.  Carcinomas of the true vocal cord limited to the middle third of the true vocal cord and not impairing mobility of the cord are treated with radiation therapy or cordectomy with an overall five-year survival rate of 85 to 95 percent.  Because cordectomy causes permanent hoarseness and irradiation usually returns the voice to normal, radiation therapy is the treatment of choice. The likelihood of metastasis in early carcinoma of the true vocal cord is very slight.


The mobility of the vocal cord becomes impaired in more advanced carcinomas as a result of invasion of the intrinsic musculature and cartilage.  With invasion of the intrinsic musculature, the rate of metastasis increases.  With invasion of thyroid cartilage, the rate of five-year survival with radiation therapy decreases precipitously.  Operation becomes the treatment of choice for lesions that involve the anterior commissure where cartilage is invaded and for larger glottic lesions in which the mobility of the true vocal cord is impaired. A hemilaryngectomy can be performed to preserve the phonatory and sphincter functions.  In more advanced cases, total laryngectomy is required, combined with a radical neck dissection for metastases.