Two Epstein-Barr Virus-Related Serologic Antibody Tests in Nasopharyngeal Carcinoma Screening: Results From the Initial Phase of a Cluster Randomized Controlled Trial in Southern China

Abstract

A nasopharyngeal carcinoma (NPC) mass screening trial using a combination of immunoglobulin A antibodies to Epstein-Barr virus capsid antigen and nuclear antigen-1 by enzyme-linked immunosorbent assay in addition to indirect mirror examination in the nasopharynx and/or lymphatic palpation (IMLP) was conducted in southern China. Cantonese aged 30-59 years residing in 2 cities randomly selected by cluster sampling, Sihui and Zhongshan, were invited to participate in this screening from May 2008 through May 2010. Participants were offered fiberoptic endoscopy examination and/or pathologic biopsy if their serologic tests reached our predefined level of high risk or if results from the physical examination indicated possible cancer (i.e., were IMLP positive). A total of 28,688 individuals were voluntarily screened in the initial round. The overall NPC detection rate was 0.14% (41/28,688) with an early diagnosis rate of 68.3% (28/41) during the first year of follow-up. Thirty-eight of 41 cases (92.7%) were detected among the high-risk group, and 7 of 41 cases (17.1%) were detected among the IMLP-positive group. The 2 Epstein-Barr virus serologic tests by enzyme-linked immunosorbent assay could be a feasible alternative for NPC screening in endemic areas. Further follow-up is needed to examine whether screening has an effect on decreasing mortality from NPC in these areas.

Epstein–Barr Virus Serology as a Potential Screening Marker for Nasopharyngeal Carcinoma among High-Risk Individuals from Multiplex Families in Taiwan

“…Our results that point to the utility of EBNA1 IgA antibody as a sensitive screening marker are further supported by large, ongoing NPC screening trials being conducted in China in areas with high endemic rates of NPC. [23–27] The sensitivity of the EBNA1 IgA assay utilized in that setting to diagnose NPC within a year of screening approached 90% and illustrated application of this screening tool in a general population setting for identifying those most likely to be harboring prevalent NPC. [28] However, it should be noted that the performance characteristics of any EBNA1 IgA test differ if applied to detect prevalent NPC that will present clinically within the following year versus incident NPC that will develop and present over the course of five years.…”

“…[14] However, general population screening with EBNA1 IgA might be more feasible in high-risk areas such as the Guangdong province of China (NPC incidence = 50 × 10 5 ). [23] (Supplemental Table 1)…”

Multiparametric Detection of Antibodies against Different EBV Antigens to Predict Risk for Nasopharyngeal Carcinoma in a High-Risk Population of China

“…Previous studies revealed considerable heterogeneity in antibody responses to individual proteins in nasopharyngeal carcinoma patients, which suggested that single antibody detection is insufficient to meet the needs of nasopharyngeal carcinoma diagnosis and combined detection is necessary (27,28).…”

Cancer Prevention Research in China

“…Elevated levels of antibodies against EBV in the lytic phase are important predictive markers for NPC risk (57). Recently, 2 EBV-related serologic antibody-based (EBV VCA/IgA and EBNA1/IgA) ELISA were used in the initial phase of a randomized trial in Southern China (67). EBV microRNAs, which are present at functional levels in NPC tissues and in serum of patients with NPC (68), could be developed as a quantitative serum-based screening assay for NPC in the future.…”