Simple Inexpensive Test Screens for Esophageal Cancer

Cancer of the esophagus claims more than 400,000 lives around the world each year. With no efficient, reliable method of screening for the disease, by the time symptoms become apparent, it's often too late to save the patient.

In 2016, the USA saw nearly 17,000 new cases diagnosed and about 16,000 deaths from cancer of the esophagus. Those numbers have increased sharply in recent years. The five-year survival rate for people with cancer confined to the esophagus is 43%. When it spreads to nearby tissues or organs, that rate falls to 23%, and esophageal cancer that spreads to distant parts of the body offers a five-year survival rate of only 5%.

Scientists from Johns Hopkins University School of Medicine (Baltimore, MD, USA) and their associates sought to develop a Barrett's esophagus (BE) detection method based on methylation status in cytology samples captured by EsophaCap using a streamlined sensitive technique, known as methylation on beads (MOB).

The principle behind the EsophaCap is simple. The patient swallows a small capsule that has a long string attached to it. After the capsule makes its way down the esophagus and into the stomach, a process that takes only a minute or so the gelatin coating on the capsule begins to dissolve. From that capsule emerges a 2-centimeter polyurethane sponge, still attached to the string, much of which still hangs from the patient's mouth. The screener gently pulls the string and the sponge begins its return journey, out of the stomach, into the esophagus and, finally, out of the patient's mouth.

The team administered the EsophaCap test to 94 people over the course of the study. Eighty-five percent of subjects were able to swallow the capsule, with 100% successful sponge retrieval. Endoscopic evaluation of the patients after EsophaCap administration and showed no evidence of bleeding, pain, trauma or other adverse reactions to the test. The scientists employed methylation on beads (MOB) to extract and bisulfite-convert DNA, followed by quantitative Methylation-Specific polymerase chain reaction (qMSP) to assess methylation levels of eight previously selected candidate markers.

The authors reported that in the training set, five of eight candidate methylation biomarkers (p16, HPP1, NELL1, TAC1, and AKAP12) were significantly higher in BE patients than in controls. They built a 4-biomarker-plus-age lasso regression model for BE diagnosis. The AUC was 0.894, with sensitivity 94.4% and specificity 62.2% in the training set. This model also performed with high accuracy for BE diagnosis in an independent test set: AUC= 0.929 with sensitivity of 78.6% and specificity of 92.8%. The authors concluded that EsophaCap, in combination with an epigenetic biomarker panel and the MOB method, is a promising, well-tolerated, low-cost esophageal sampling strategy for BE diagnosis.

Stephen J. Meltzer, a gastroenterologist and a professor of medicine and oncology and senior author of the study, said, “It's actually possible to miss early cancerous cells using endoscopy with biopsy and most patients with Barrett's don't ever undergo endoscopy. Right now, we're confident that we have the tools to identify this type of cancer. But we previously lacked a way to collect enough genetic material to confidently determine a patient's diagnosis. We believe that EsophaCap now provides a solution to this serious problem.” The study was published on January 22, 2019, in the Clinical Cancer Research.

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Johns Hopkins University School of Medicine