Epidemiologic Evolution of Esophageal Cancer

Driven by changing social and behavioral practices, the epidemiology of gastroesophageal cancer in the U.S. underwent dramatic evolution in the 20th Century. In terms of absolute and relative numbers, the incidence of esophageal cancer started to rise in the mid-1970s and increased steadily year over year until about 2004. Since then rates have remained stable, and the American Cancer Society (ACS) estimates 22,530 new cases of esophageal cancer for 2026, with men accounting for almost 80% of the cases.

However, the total number of cases has played a lesser role in the epidemiologic evolution as compared with qualitative changes. Throughout most of the 20th Century, esophageal squamous-cell carcinoma (ESCC) predominated, accounting for up to 90% of the annual incidence. Beginning in the mid-1970s, the incidence of esophageal adenocarcinoma (EAC) increased dramatically, continuing into the 21st Century. Today EAC accounts for more than 60% of all new cases of esophageal cancer in the U.S., and the incidence of ESCC has decreased proportionally. That contrasts with the worldwide incidence, wherein ESCC accounts for about 90% of new cases each year.

The U.S. is not alone in the epidemiologic evolution.

“In the Western world — Western Europe, Canada, Australia — that’s where you see the adenocarcinoma variety of esophageal cancers,” Michael K. Gibson, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tennessee, told MedPage Today. “The difference is probably due to diet and the environment, for the most part.”

Although ESCC predominates throughout Asia, rates of EAC have begun to increase in countries that have increasingly adopted a Western-style diet, he added.

Squamous-cell cancers are common to components of the aerodigestive tract — esophagus, lungs, head, and neck — “anything that includes swallowing and breathing,” said Gibson. Exposure to smoking, pickled foods, smoked foods, and alcohol is thought to be the primary cause of cancers in those tissues.

In the U.S. and other developed nations, esophageal cancers more often arise in the lower part of the esophagus, particularly the gastroesophageal junction, and develop into adenocarcinoma. Gastroesophageal adenocarcinoma is closely associated with obesity, gastroesophageal reflux disease, and Barrett’s esophagus.

“Normal squamous cells get fooled into thinking they’re more a part of the small intestine or duodenum,” said Gibson. “When the valve that separates the esophagus from the stomach … is weakened, you get reflux, not only acid but also bile salts. When the epithelium gets exposed to acid and bile salts, the cells have to change to become more resistant and able to tolerate the acid and salts, and with the transformation you have metaplasia, which is a precursor to adenocarcinoma.”

Although the obesity epidemic continues unabated, no wild upward swings in gastroesophageal adenocarcinoma have occurred over the past 20 years or so, noted Farhad Islami, MD, PhD, head of cancer disparity research for the ACS in Atlanta. No clear explanation exists, but the lack of major changes could indicate a moderating effect between risk factors.

“Although obesity is a major risk factor in the U.S., we know that smoking is a much stronger risk factor for esophageal cancer overall, for both squamous cell carcinoma and adenocarcinoma,” he told MedPage Today. “Maybe the trend we see is kind of the combination of trends in smoking and obesity. Smoking is going down, obesity is going up. Maybe the reason we don’t see a huge increase in adenocarcinoma in the esophagus is because smoking is very low and continues to go down and kind of offsets the effect of increases in obesity.”

Further evidence of possible interplay between risk factors comes from an age difference in the division between squamous-cell and adenocarcinoma. ESCC remains higher among adults 65 and older, said Islami. One possible explanation is that older smokers and former smokers have had longer exposure to that key risk factor. Smoking prevalence is much lower among younger adults.

For years, esophageal cancer was one of the fastest-rising cancers in the U.S. The rate slowed in recent years, for reasons that are not entirely clear, said Gibson. Even though the overall rate of obesity continues to rise, dietary changes and weight loss cannot be entirely excluded.

“I wonder if the rate will go down more with use of GLP-1 agonists,” said Gibson. “We’ll have to wait and see. It will be a slow process, at least 10 years and probably 15-20 years because that’s how long it takes for a precursor to turn into cancer. I have a lot of hope for that because if the Barrett’s goes down, so will the cancer.”

The slowing of the rate of increase in esophageal cancer despite the persistence of the obesity epidemic raises the question of whether “we were missing something over the past 10-20 years,” said Gibson. “If we haven’t caught up with the GLP-1 curve, which is coming down the road, why is it slowing down?”

Looking ahead, Islami said he is particularly interested in looking at esophageal cancer trends in different age groups, specifically how the obesity epidemic will affect esophageal cancer rates in younger adults.

“We are already seeing an increase in the incidence of colorectal cancer among people younger than 50,” he said. “I am very interested to see whether a similar thing is going to happen with esophageal cancer and gastric cardia adenocarcinoma. Those two are very similar to each other in terms of risk factors and also most of the time in trends.”

A study published a few years ago showed an increase in esophageal cancer in adults younger than 50. Based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results registry program, the analysis also showed that younger patients were more likely to have advanced-stage diagnoses.