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.

More than 75% of nasopharyngeal carcinoma (NPC) patients have already developed local or regional spread at diagnosis, which hampers effective treatment and results in a poor prognosis. It is essential to characterize more sensitive and specific biomarkers for screening of high risk individuals and assessment of NPC treatment effectiveness. NPC is an Epstein–Barr virus (EBV) associated tumor in which only a few viral proteins but more than 20 BamHI A rightward transcripts (BART) microRNAs are detected, at abundant levels. We hypothesized that these BART microRNAs may be novel biomarkers for NPC. Systematic analysis of EBV BART microRNA expression profiles in EBV latently infected Mutu I and Mutu III cell lines, EBV‐harboring NPC and noncancerous NP cells found that miR‐BART3, miR‐BART7 and miR‐BART13 microRNAs are highly expressed and regularly secreted into the extracellular environment of NPC cells. These BART microRNAs were evaluated for used as potential NPC biomarkers. Analysis of plasma specimens obtained from NPC patients (n = 89), and healthy (n = 28) and non‐NPC tumor patient controls (n = 18) found levels of both miR‐BART7 and miR‐BART13, but not miR‐BART3, to be distinctly presence among NPC patients, with elevated levels being particularly apparent among patients with advanced disease. Receiver operating characteristic curve analysis combining miR‐BART7 and miR‐BART13 levels produces a 90% predictive value for the presence of NPC. Analysis of 41 NPC patients before and after radiotherapy showed that miR‐BART7 and miR‐BART13, but not miR‐BART3, were diminished after treatment. These results indicate that EBV microRNAs, miR‐BART7 and miR‐BART13, may constitute useful new serological biomarkers for diagnosis of NPC and prediction of treatment efficacy.

Significance: Nasopharyngeal carcinoma (NPC) is a valuable cancer model to study the interaction of host genetics, viral infection, and environment in tumorigenesis. Little is known about the genetic basis for the remarkably distinct geographical distribution of NPC. We used a whole-exome sequencing approach to identify the genetic alterations associated with NPC susceptibility and revealed a strong link between macrophage-stimulating 1 receptor ( MST1R ) and NPC early-age onset (age of ≤20 y). MST1R is critical for innate immunity and plays an important role for host defense against viral infection. We further discovered that an interaction network involved in the MST1R/14-3-3 complex was frequently deregulated by genetic alterations in NPC. Our findings provide new insights in the pathogenesis of NPC by highlighting the involvement of the MST1R-mediated signaling pathways.

BACKGROUND: The utility of circulating Epstein‐Barr Virus (EBV) DNA as a tumor marker for nasopharyngeal carcinoma (NPC) detection suggests that it might improve the diagnostic performance of anti‐EBV antibody markers in NPC screening. In this study, the authors evaluated whether circulating EBV DNA load is capable of distinguishing NPC patients from high‐risk individuals who have positive anti‐EBV antibodies.METHODS: In a population‐based NPC screening trial in Sihui City and Zhongshan City, Guangdong Province, China, the authors previously identified 862 high‐risk participants with 2 screening markers, immunoglobulin A (IgA) antibodies to EBV capsid antigen (VCA/IgA) and nuclear antigen‐1 (EBNA1/IgA). In the current study, real‐time polymerase chain reaction was used to measure the baseline plasma EBV DNA load among 825 participants (97%). Follow‐up was extended to the end of 2011 to evaluate the diagnostic and predictive values of plasma EBV DNA load.RESULTS: By using 0 copies/mL as the cutoff value, plasma EBV DNA had a sensitivity of 86.8% (33 of 38 patients) for NPC detected within the first year of follow‐up, yielding a positive predictive value of 30% (33 of 110 participants) and a negative predictive value of 99.3% (696 of 701 participants). The patients who had early stage NPC had lower sensitivity (81.5%; 22 of 27 patients) than those who had advanced NPC (100%; 11 of 11 patients). For the 14 patients who had NPC detected after 1 year of follow‐up, only 50% (7 of 14 patients) tested positive for EBV DNA at baseline.CONCLUSIONS: The plasma EBV DNA load may improve the accuracy of diagnosing NPC in high‐risk individuals, but it appears to have limited value in screening patients who have early stage NPC and predicting NPC development. Cancer 2014;120:1353–1360. © 2014 American Cancer Society.

A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)–based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program.

We have evaluated the performance of 3 new EBV ELISA for the diagnosis of nasopharyngeal carcinoma (NPC). The tests were specific for EBNA 1 IgA, EBNA 1 IgG and zta IgG, respectively. Their distinct antigenic specificity permits these assays to be used in concert in an approach that differentiates patients and apparently healthy subjects on the basis of their antibody spectrum. By so exploiting a distinguishing feature of NPC first described by the late Werner Henle that the patients sustain high levels of a broad spectrum of serum EBV antibodies, this approach achieved a sensitivity of 92% and a specificity of 93%, surpassing the performance of each of these assays individually. The enhanced performance is especially useful in population screening. It was shown that relative risk of NPC sustained by apparently healthy subjects residing in a high incidence area for NPC in the Pearl River estuary in Southern China may vary according to EBV antibody spectrum. The risk of the cancer was markedly reduced with odds ratios of 0.009 for 59% of those who had low level of all 3 antibodies. The risk was increased as antibody spectrum broadens and the risk was the highest with an odds ratio of 138 for 0.4% of those who had high levels of all 3 antibodies. Thus, EBV antibody spectrum may serve to guide follow‐up measures for early detection of the cancer and/or risk counseling according to level of the risk of the cancer sustained by the screened individuals.