Liquid biopsy for NPC screening proves effective in large-scale study
The use of noninvasive liquid biopsy for nasopharyngeal cancer (NPC) screening is found to be effective in a study in more than 20,000 participants in Hong Kong.
The study, conducted by investigators from the Chinese University of Hong Kong (CUHK) and published in the New England Journal of Medicine recently, showed significantly improved 3-year progression-free survival (PFS) rate and a higher proportion of stage I or II NPC in cases detected by liquid biopsy compared with a historical cohort. [N Engl J Med 2017, doi: 10.1056/NEJMoa1701717]
Between 2013 and 2016, 20,174 healthy men aged 40–62 years were tested for Epstein-Barr virus (EBV) DNA in plasma. Participants with positive results were retested about 4 weeks later. Those with persistent plasma EBV DNA positivity underwent nasal endoscopic examination and MRI to confirm NPC diagnosis.
EBV DNA was detected in the plasma samples of 1,112 participants (5.5 percent), and 309 participants (1.53 percent) had persistently positive results. “Among these 309 participants, 300 underwent endoscopic examination and 275 underwent MRI,” reported investigator Professor Allen Chan of the Department of Chemical Pathology, CUHK. “Nine participants declined further investigations.”
NPC was confirmed in 34 participants. Remarkably, a significantly higher proportion of these patients had stage I or II disease compared with those from the 2013 Hong Kong Cancer Registry (71 vs 20 percent; p<0.001). The 3-year PFS rate among the 34 participants was also superior to a historical cohort of 1,278 age- and sex-matched NPC patients in Hong Kong (97 vs 70 percent; hazard ratio, 0.10; p<0.001).
“Identifying NPC at an earlier stage means that patients can receive more timely and effective treatments, resulting in PFS improvements and reductions in treatment-related morbidity,” said Chan.
“The pathogenesis of NPC is closely associated with EBV. Circulating cancer-derived EBV DNA in plasma has been established as a tumour marker for NPC, with a sensitivity of 96 percent and specificity of 93 percent,” he explained. [Cancer Res 1999;59:1188-1191; J Clin Oncol 2006;24:5414-5418] “Interestingly, EBV DNA in plasma consists of short DNA fragments released by NPC cells, rather than being associated with viral particles.” [Cancer Res 2003;63:2028-2032]
“The positive NPC predictive value of 11 percent [34 of 309] in our study is superior to the typical 3 percent with existing blood-based tumour markers in a population-based setting,” said investigator Professor Dennis Lo of CUHK’s Department of Chemical Pathology. “In 19,865 participants who tested negative for plasma EBV DNA, only one developed NPC within 1 year. This translates to a sensitivity of 97.1 percent and a negative predictive value of 99.995 percent.”
“Considering the shift in NPC stage distribution and potential for significant improvements in mortality and morbidity, plasma EBV DNA testing appears to be a feasible practice in regions with high NPC prevalence,” he continued. “The cost of the test is around HKD 240. We hope to make it readily available in the market in 3 years.”