Johns Hopkins Researcher Develops Simple Biomarker Test for Esophageal Cancer

Published in Inside Tract - Spring 2022

In a small but rigorous pilot study, Johns Hopkins Medicine researchers demonstrated that a minimally invasive biomarker-based strategy they developed was 90% successful in detecting the most common form of esophagus cancer.

Gastroenterologist Stephen Meltzer and his lab team published results of the case-control study, which combined a biomarker panel that predicts esophageal squamous cell carcinoma (ESCC) with a small sponge designed to collect cell samples from people at risk of developing the disease.

Cancer of the esophagus is the seventh most common cancer and the sixth most lethal form of the disease in the world, claiming 544,000 lives in 2020. While relatively rare in the United States, the disease is more common in stretches of Asia, as well as in southern and eastern Africa. Early detection is key to surviving the disease, but by the time symptoms — such as trouble swallowing, weight loss, anemia or bleeding — become apparent, the cancer is often too advanced to cure. The five-year survival rate for this cancer is less than 20%.

During the screening test, the patient swallows the sponge, which is compressed inside a capsule that has a string attached to it. After the capsule has made its way to the bottom of the esophagus, its coating dissolves, allowing the sponge to expand to roughly the size of a nickel with the string still attached. A clinician gently pulls the string until the sponge emerges from the patient’s mouth.

The sample, which is now rich with cells from the entire length and circumference of the esophagus, is sealed in a tube and sent to be tested against the specific DNA-based biomarker panel.

Meltzer says the test could bring efficient, inexpensive and noninvasive screening to areas of the world where access to health care is scarce.

“With esophageal cancer, diagnosis is a matter of life and death,” says Meltzer, who has dedicated decades of his career to the detection and prevention of this disease. “There are tests to detect Barrett’s esophagus and esophageal carcinoma. But currently, there is no inexpensive, minimally invasive screening tool that can be used regularly to diagnose people who are specifically at risk for esophageal squamous cell carcinoma.”

Meltzer adds that a key risk factor for ESCC, especially in women, is exceptionally high exposure to wood smoke in poorly ventilated indoor spaces, which is a common situation in areas where esophageal cancer is high. Other risk factors include smoking tobacco and drinking alcohol.

Meltzer’s research team administered the sponge biomarker test to 94 people, including many in Uganda (a nation with a high-risk population) as well as patients at The Johns Hopkins Hospital. The final biomarker algorithm used to detect ESCC yielded an “area under the curve” value of 0.94 — generally considered very strong in biomarker research studies.

After the procedures, researchers found no evidence of bleeding, pain, trauma or other serious adverse reactions among participants in the study.

In developed nations such as the United States, observation and cell samples obtained via an endoscope are the standard of care to screen for esophageal squamous dysplasia, a typically asymptomatic lesion recognized as a precursor to cancer. But studies have revealed a paucity of both endoscopes and clinicians trained to use them in developing areas, such as eastern and southern African nations, where ratios range as high as one endoscopist to 2 million people.

“These findings have global implications, with perhaps the biggest impact on lower-income countries with limited access to health care and resources,” says Meltzer. “We may be able to save thousands of lives if we can detect this disease early enough to intervene.”