Performance and Operational Feasibility of Epstein-Barr Virus–Based Screening for Detection of Nasopharyngeal Carcinoma: Direct Comparison of Two Alternative Approaches
Pei‐Jen Lou, W.K. Lam, Wan-Lun Hsu, Ruth M. Pfeiffer, Kelly J. Yu, Charles Ming Lok Chan, Vicky C.T. Lee, Tseng‐Cheng Chen, Shyuang‐Der Terng, Yung‐An Tsou, Yi‐Shing Leu, Li‐Jen Liao, Yen‐Liang Chang, Yin-Chu Chien, Cheng‐Ping Wang, Ching-Yuan Lin, Chun‐Hung Hua, Jehn-Chuan Lee, Tsung‐Lin Yang, Chuhsing Kate Hsiao, Ming‐Shiang Wu, Ming-Hsui Tsai, Skye Hung‐Chun Cheng, Allan Hildesheim, Chien‐Jen Chen, K.C. Allen Chan, Zhiwei Liu, on behalf of the GEV-NPC Study Group, Wan-Lun Hsu, Yin-Chu Chien, Chien‐Jen Chen, Allan Hildesheim, Ruth M. Pfeiffer, Zhiwei Liu, Kelly J. Yu, Cheng-Ping Wang, Tsung‐Lin Yang, Pei‐Jen Lou, Chun‐Nan Chen, Tseng‐Cheng Chen, Chih-Feng Lin, James Jer‐Min Jian, Skye Hongiun Cheng, Yu-Chen Tsai, Yih‐Lin Chung, Jia‐Shing Wu, Ming-Jiung Liu, Kuei-Kang Huang, Mei-Hua Tsou, Hsin-Hsuan Chen, Ching-Yuan Lin, Shyuang‐Der Terng, Fang-Yin Lin, Hsin-I Huang, Hung-Chun Cheng, Yung‐An Tsou, Chun-Hung Hua, Ming-Hsui Tsai, Yi‐Shing Leu, Jehn-Chuan Lee, Li-Jen Liao, Yen‐Liang Chang, Chuhsing Kate Hsiao, Ming‐Shiang Wu
Abstract
PURPOSE: Two Epstein-Barr virus (EBV)-based testing approaches have shown promise for early detection of nasopharyngeal carcinoma (NPC). Neither has been independently validated nor their performance compared. We compared their diagnostic performance in an independent population. METHODS: We tested blood samples from 819 incident Taiwanese NPC cases (213 early-stage, American Joint Committee on Cancer version 7 stages I and II) diagnosed from 2010 to 2014 and from 1,768 controls from the same region, frequency matched to cases on age and sex. We compared an EBV antibody score using immunoglobulin A antibodies measured by enzyme-linked immunosorbent assay (EBV antibody score) and plasma EBV DNA load measured by real-time PCR followed by next-generation sequencing (NGS) among EBV DNA-positive individuals (EBV DNA algorithm). RESULTS: = .514). For regions with a NPC incidence of 20-100/100,000 person-years (eg, residents in southern China and Hong Kong), these two approaches yielded similar numbers needed to screen (EBV antibody score: 5,656-1,131; EBV DNA algorithm: 5,365-1,073); positive predictive values ranged from 0.4% to 1.7% and 1.0% to 4.7%, respectively. CONCLUSION: We demonstrated high sensitivity and specificity of EBV antibody and plasma EBV DNA for NPC detection, with slightly inferior performance of the EBV antibody score. Cost-effectiveness studies are needed to guide screening implementation.