Note: Separate PDQ summaries on Esophageal Cancer Prevention, Esophageal Cancer Treatment (Adult), and Levels of Evidence for Cancer Screening and Prevention Studies are also available.
Based on fair evidence, screening would result in no (or minimal) decrease in mortality from esophageal cancer in the U.S. population.
Description of the Evidence
|Study Design: Evidence from cohort or case-control studies.|
|Internal Validity: Fair.|
|Consistency: Multiple studies.|
|Magnitude of Effects on Health Outcomes: Small positive.|
|External Validity: Poor.|
Based on solid evidence, screening would result in uncommon but serious side effects associated with endoscopy which may include perforation, cardiopulmonary events and aspiration, and bleeding requiring hospitalization. Potential psychological harms may occur in those identified as having Barrett esophagus who may consider themselves to be ill even though their risk of developing cancer is low.
Description of the Evidence
|Study Design: Evidence obtained from cohort or case-control studies.|
|Internal Validity: Fair.|
|Consistency: Multiple studies, large number of participants.|
|Magnitude of Effects on Health Outcomes: Fair evidence for no reduction in mortality; good evidence for uncommon but serious harms.|
|External Validity: Poor.|
Natural History, Incidence, and Mortality
In 2020, it is estimated that 18,440 Americans will be diagnosed with esophageal cancer, and 16,170 will die of this malignancy. Of the new cases, it is estimated that 14,350 will occur in men and 4,090 will occur in women.
Two histologic types account for the majority of malignant esophageal neoplasms: adenocarcinoma and squamous carcinoma. The epidemiology of these types varies markedly. In the 1960s, squamous cell cancers comprised more than 90% of all esophageal tumors. The incidence of esophageal adenocarcinomas has risen considerably for the past two decades, such that it is now more prevalent than squamous cell cancer in the United States and Western Europe, with most tumors located in the distal esophagus. Although the overall incidence of squamous cell carcinoma of the esophagus is declining, this histologic type remains six times more likely to occur in black men than in white men. Incidence rates generally increase with age in all racial/ethnic groups but squamous cell cancer is consistently more common in blacks than in whites. Incidence rates are higher in white men compared with black men in all age groups. In women, the incidence rates are higher in blacks through age 69 years, at which point the rates become higher in whites.
While risk factors for squamous cell carcinoma of the esophagus have been identified (such as tobacco, alcoholism, malnutrition, and infection with human papillomavirus), the risk factors associated with esophageal adenocarcinoma are less defined. The most important epidemiological difference between squamous cell cancer and adenocarcinoma, however, is the strong association between gastroesophageal reflux disease (GERD) and adenocarcinoma. The results of a population-based case-control study suggest that symptomatic gastroesophageal reflux is a risk factor for esophageal adenocarcinoma. The frequency, severity, and duration of reflux symptoms were positively associated with increased risk of esophageal adenocarcinoma.[6,7,8]
Long-standing GERD predisposes to Barrett esophagus, the condition in which an abnormal intestinal epithelium replaces the stratified squamous epithelium that normally lines the distal esophagus. The intestinal-type epithelium of Barrett esophagus has a characteristic endoscopic appearance that differs from squamous epithelium. Dysplasia in Barrett epithelium represents an alteration of the columnar epithelium that may progress to invasive adenocarcinoma.
An interesting hypothesis relates the rise in incidence of esophageal adenocarcinoma to a declining prevalence of Helicobacter pylori infection in Western countries. Reports have suggested that gastric infection with H. pylori may protect the esophagus from GERD and its complications. According to this theory, H. pylori infections that cause pangastritis also cause a decrease in gastric acid production that protects against GERD. Patients whose duodenal ulcers were treated successfully with antibiotics developed reflux esophagitis twice as often as those in whom infection persisted.
Past use of lower esophageal sphincter (LES)-relaxing drugs was positively associated with risk of esophageal adenocarcinoma. Among daily, long-term users (>5 years) of LES-relaxing drugs, the estimated incidence rate ratio was 3.8 (95% confidence interval [CI], 2.2–6.4) compared with persons who had never used these drugs. Gastric cardia adenocarcinoma and esophageal squamous cell carcinoma were not associated with use of LES-relaxing drugs.
There exists a strong relationship between body mass index (BMI) and esophageal adenocarcinoma. The adjusted odds ratio (OR) was 7.6 (95% CI, 3.8–15.2) among persons in the highest BMI quartile compared with persons in the lowest. Obese persons (those with BMI >30 kg/m2) had an OR of 16.2 (95% CI, 6.3–41.4) compared with the leanest persons (BMI <22 kg/m2). Esophageal squamous cell carcinoma was not associated with BMI.
Squamous Cell Cancer
Squamous cell carcinoma of the esophagus does not have a highly prevalent predisposing condition, although the incidence increases in persons who have had long-standing exposure to tobacco and alcohol, achalasia, head and neck squamous cell cancer attributable most likely to long-standing alcohol and/or tobacco exposure, tylosis,[4,5] history of lye ingestion, celiac sprue, and, in South America and China, hot liquid ingestion. The etiological role of human papillomavirus infection in squamous cell cancer is under study.[9,10]
Efforts at early detection of squamous cell cancer of the esophagus have concentrated on cytological or endoscopic screening of populations in countries where there is a high incidence. While these programs have demonstrated that it is possible to detect squamous cell cancers in an early asymptomatic stage, a study from China assessed one-time endoscopic screening on the outcome of patients with esophageal cancer. In this study, communities were chosen nonrandomly in Cixian County, Hibei Province; 14 villages in the north were intervention communities and ten villages in the south were control communities. The intervention was one-time endoscopy, completed by experts, using Lugol's iodine staining to identify dysplasia or occult cancer. After biopsy was obtained and read, dysplasia and occult cancers were treated by endoscopic mucosal resection or argon plasma coagulation. Among the 6,827 participants aged 40 to 69 years in the intervention group, 3,319 volunteers were screened. Among the 6,200 participants aged 40 to 69 years in the control group, 797 individuals were interviewed. Outcome in each group was monitored to assess incidence and mortality of esophageal squamous cancer. In a 10-year follow-up, there were 542 cases of fatal esophageal squamous cell carcinoma (ESCC), a reduction in cumulative mortality from 5.05% in the control group to 3.35% in the intervention group (P < .001), and lower incidence of ESCC in the intervention group (5.92% vs. 4.17%, P < .001). Potential weaknesses of the study include the following:
Esophageal cytological screening studies have been reported from China,[12,13] Iran, South Africa,[15,16] Italy, and Japan. In the United States, such efforts have been focused on individuals perceived to be at higher risk.[19,20] Studies of primary endoscopic screening have been reported from France  and Japan.
Comparisons of both Chinese and U.S. cytological diagnoses with concurrent histological findings showed low (14% to 36%) sensitivities for the cytological detection of biopsy-proven cancers. Specificity ranged from 90% to 99% with a positive predictive value of 23% to 94%. The development of uniform and accurate cytological criteria will require formal cytological-histological correlation studies of esophageal lesions. Such studies should become more feasible with the increasing availability of endoscopy in high-risk populations.
The efficacy of surveillance cytology or endoscopy for high-risk patients with tylosis or long-standing achalasia is not known.
Adenocarcinoma of the Esophagus
Considerable debate has ensued concerning the risk of cancer in patients with Barrett esophagus. Prospective studies have reported annual esophageal cancer incidence rates ranging from 0.2% to 1.9%. Concern over publication bias has led some authors to suggest that the risk may be lower than the literature suggests. A risk of 0.5% per year for development of adenocarcinoma is now thought to be a reasonable estimate for Barrett esophagus.
Barrett esophagus is strongly associated with gastroesophageal reflux disease (GERD), and the changes of Barrett esophagus can be found in approximately 10% of patients who have GERD. However, GERD is very common; surveys have found that approximately 20% of adult Americans experience symptoms of GERD, such as heartburn, at least once each week. The likelihood of finding Barrett esophagus on endoscopy is related to the duration of symptoms of gastroesophageal reflux. In a series of 701 individuals, 4% of those with symptoms for less than 1 year had Barrett esophagus on endoscopy, whereas Barrett esophagus was found in 21% of those with more than 10 years of symptoms of GERD. It has been estimated that physicians identify only approximately 5% of the population who have Barrett esophagus. There is insufficient evidence that population screening for Barrett esophagus reduces cancer mortality.[29,30]
Surveillance of Barrett esophagus involves the use of tests to identify preneoplastic changes or curable neoplasms in patients who are known to have Barrett esophagus. Certain factors are essential in the implementation of an effective surveillance protocol, including low risk of the surveillance method, correct histological diagnosis of dysplasia, proof that surgical resection for high-grade dysplasia will decrease the risk of cancer, and successful resection of cancer. The interval between endoscopic evaluations is typically determined by histologic findings, in accordance with published guidelines by gastroenterological committees. GERD should be treated prior to surveillance endoscopy to minimize confusion caused by inflammation in the interpretation of biopsy specimens. The technique of random, four-quadrant biopsies taken every 2 cm in the columnar-lined esophagus for standard histological evaluation has been recommended by some clinicians. For patients with no dysplasia, surveillance endoscopy at an interval of every 2 to 3 years has been recommended. For patients with low-grade dysplasia, surveillance every 6 months for the first year has been recommended, followed by annual endoscopy if the dysplasia has not progressed in severity. For patients with high-grade dysplasia, two options have been recommended: surgical resection or repeated endoscopic evaluation until the diagnosis of intramucosal carcinoma is made. Although widely adopted in clinical practice, these practices are based on uncontrolled series and the opinion of expert gastrointestinal endoscopists and pathologists.
Evidence of Harm
Screening for esophageal cancer by the use of blind nonendoscopically directed balloon cytological sampling for squamous cell carcinoma is minimally inconvenient and uncomfortable. Endoscopic screening for esophageal adenocarcinoma is expensive, inconvenient, and usually requires sedation.
Complications such as perforation and bleeding can occur. The incidence of complications including perforation, respiratory arrest, and myocardial infarction, has been estimated to be 0 to 13 per 10,000 procedures with an associated mortality of 0 to 0.8 per 10,000 procedures.[34,35]
Individuals who are informed they have Barrett esophagus may consider themselves to be ill even though their risk of developing cancer is very low.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Added text to state that incidence rates are higher in white men compared with black men in all age groups; in women, the incidence rates are higher in blacks through age 69 years, at which point the rates become higher in whites (cited Howlader et al. as reference 4).
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Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about esophageal cancer screening. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
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Levels of Evidence
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PDQ® Screening and Prevention Editorial Board. PDQ Esophageal Cancer Screening. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/esophageal/hp/esophageal-screening-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389241]
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Last Revised: 2020-03-30
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