Etiology

There is overwhelming evidence that smoking increases the risk of laryngeal cancer.[8]​ People who smoke >30 cigarettes per day have a 7-fold increased risk of laryngeal cancer, compared with never smokers.[8]​ The relative risk for laryngeal cancer is greater than 10 for people who have smoked for more than 40 years, compared with never smokers.[9]​ Sixty-three percent of deaths from laryngeal cancer are attributable to smoking.[5]​

Alcohol consumption is a risk factor for laryngeal cancer.[9] The relative risks of laryngeal cancer are 1.38 for people who consume the equivalent of two 12 fluid-ounce containers of beer daily and 3.95 for eight 12 fluid-ounce containers (95% CI).[10]​

Concurrent tobacco smoking and consumption of alcohol have a multiplicative effect on the risk of laryngeal cancer.[9][11] Estimated relative risks range from 8.0 to >100.0.[9]​

GERD is associated with a 2- to 3-fold increased risk of developing laryngeal cancer.[12][13]​​​ Alkaline bile reflux in patients with achlorhydria who have undergone gastrectomy may increase the risk of malignant lesions of the larynx.[14]​ Patients may have a distant history of radiation therapy to the neck.[15]​​​​​​​ Vocal cord dysplasia is associated with the development of laryngeal cancer.[16][17][18]​​

There may be a genetic predisposition. One case-control study reported a 3.8-fold increased risk of laryngeal cancer in people with a family history of laryngeal cancer in a first-degree relative.[19] Rates of chromosomal aberration and fragile site expression were higher in patients with head and neck cancer and their first-degree relatives than in a control group.[20]​ A mutation in the p16 tumor suppressor gene has been identified in a family with a high incidence of head and neck cancer.[21]​​

Pathophysiology

Laryngeal cancer arises from progressive accumulation of genetic alterations that lead to selection of a clonal population of transformed cells.[22]​ Head and neck cancers (including laryngeal cancer) may require more genetic alterations in their development than other solid tumors, thus explaining the often long (20-25 years) period of latency after initial toxin exposure.[23] Carcinogenesis is induced by DNA damage, mutations, and adducts.[22]​​

Human papillomavirus (HPV) has been well described in the pathogenesis of oropharyngeal cancer, but its role in laryngeal cancer is less clear. HPV infection is detected in 28% of laryngeal cancer cases, and it is associated with a 5-fold increase in risk of laryngeal squamous cell cancer.[24]

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