Esophageal Cancer: An Updated Review

Michael DiSiena, MD; Alexander Perelman, DO; John Birk, MD; Houman Rezaizadeh, MD


South Med J. 2021;114(3):161-168. 

In This Article


EC is the sixth most common cause of cancer-related death in the world, and with a rising incidence rate, it has the seventh highest rate of new cases worldwide.[4] It is seen predominantly in males, with a male:female ratio of 2.5:1. Worldwide, SCC accounts for 87% of EC;[5] however, in North America, Australia, and Europe, AC is the predominant subtype, accounting for approximately 70% of new cases of EC.[5] The highest incidence and prevalence rates of SCC are found in southern and eastern Africa as well as eastern Asia, and the lowest rates are in western and central Africa and Central America (trends are similar for males and females).[4]

Asia has the highest incidence, prevalence, and 5-year mortality rates for EC.[4] This high-risk area stretches from northern Iran through the central Asian republics to north-central China (unofficially known as the "esophageal cancer belt"). Ninety percent of EC in this region is esophageal squamous cell carcinoma. Although the vulnerability of people in this area is not clearly understood, poor nutritional status, low intake of fruits and vegetables, and drinking beverages at high temperatures are hypothesized to be risk factors.

Interestingly, these risk factors are not seen in lower-risk areas for SCC, such as the United States and other Western countries, where smoking and excessive alcohol use are the major risk factors for SCC.[4] In addition, in the United States, the sex disparity for EC widens, with males estimated to be affected with a 3.5:1 ratio in 2019.[6] Although EC is the seventh highest cause of cancer death in the United States, it is estimated to make up just 1% of all new cancer cases.[1,6]

In the United States, 85% of AC cases are males, 95% are White, and 92% are 50 years old or older (the peak incidence is in those 80–84 years of age, with an annual incidence of 10:100,000 in this age group).[5] From 1975 to 2001, AC was one of the fastest growing cancers in the United States, increasing at approximately 8%/year, but the latest epidemiological data indicate that incidence is plateauing at approximately 2.8:100,000.[7] In the United States, SCC has been declining since the mid-1980s, with overall incidence decreasing nearly two-thirds to approximately 1.2:100,000.[7] SCC incidence remains highest among Black males.[7] The reason for the differences in epidemiological data and trends in the United States compared with the world may be rooted in the causes of AC and SCC in relation to regional lifestyle variations of risk factors and environmental exposures.