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Cell-Free DNA Shows Promise for Nasopharyngeal Cancer Screening in Prospective Study

NEW YORK (GenomeWeb) – Results from a large, prospective study suggest that monitoring for circulating, cell-free tumor DNA biomarkers can help in detecting tumors in individuals who do not yet show symptoms of the disease.

"Using nasopharyngeal carcinoma as a model, we found that it was feasible to use analysis of circulating DNA to screen for cancers in asymptomatic persons," corresponding author Dennis Lo, director of the Li Ka Shing Institute of Health Sciences and chemical pathology researcher at the Chinese University of Hong Kong, and his colleagues wrote in a study appearing in the New England Journal of Medicine today.

Lo and his colleagues focused their ctDNA search on DNA from the Epstein-Barr virus (EBV), which typically turns up in nasopharyngeal carcinoma tumors. Using EBV DNA as a marker, they searched for ctDNA in blood samples from more than 20,000 symptom-free participants, narrowing in on 1,112 individuals with EBV-positive blood samples at baseline.

The team tested the latter individuals again about a month later and picked up EBV DNA in just over one-quarter of those participants, prompting more detailed endoscopic and/or magnetic resonance imaging searches for nasopharyngeal cancer in 300 individuals. All told, the search identified 34 nasopharyngeal carcinoma cases, while one case of the disease was identified in the following months in an individual with no detectable EBV DNA in the blood.

Based on their results, the researchers estimated that the ctDNA approach, using EBV DNA as a marker, could uncover nasopharyngeal carcinoma with more than 97 percent sensitivity and nearly 99 percent specificity.

The team noted that nasopharyngeal carcinoma is relatively common in parts of Southeast Asia, where as many as 35 for every 100,000 middle-aged men are diagnosed with the disease. Given the close ties between the disease and EBV, the group decided to take a crack at using the virus as a marker to test the utility of liquid biopsies for early cancer detection.

Through nearly 150 public health education sessions held over a few years in Hong Kong, the researchers enrolled 20,174 eligible Chinese men between the ages of 40 and 62 years old — a group known from past studies to be particularly nasopharygeal carcinoma prone.

Using a real-time PCR assay, they detected EBV DNA in venous blood samples from 1,112 participants at the time of enrollment. Four weeks later, the same approach unearthed detectable DNA from EBV in 309 of those participants.

Nine of the individuals decline further testing, the team noted, including one individual who went on to be diagnosed independently with advanced nasopharyngeal carcinoma a few years later.

Of the 300 individuals who received nasal endoscopy alone or in combination with an MRI, 34 individuals were diagnosed with nasopharyngeal carcinoma. Among them: 16 individuals with stage I disease.

During two years of follow up, the researchers identified one individual with recurrent disease. On average, though, the three-year progression-free survival rate was around 97 percent. Two individuals who lacked detectable EBV DNA at baseline went on to develop the disease, they reported: one four months after enrollment and another nearly two years after the initial blood draw.  

The authors noted that their PCR-based EBV DNA tests cost $30 apiece, on average, while endoscopic tests and MRIs cost an average of $80 and $1,000 each, respectively.

"On the basis of the results of this study, to detect [one] case, 593 participants would need to be screened at a cost of $28,600," they wrote. "Considering the potential decrease in mortality and morbidity, as well as treatment-cost savings associated with the shift in stage distribution, screening for nasopharyngeal carcinoma appears to be a feasible practice in regions with a high incidence of this disease."

Lo is the founder of Chinese molecular diagnostics firm Cirina, which was acquired by Grail earlier this year. Following the publication of the NEJM study, industry analysts have speculated that Grail could be targeting the launch of a nasopharyngeal cancer screening test in Asia.