Distribution of Epstein‐Barr viral load in serum of individuals from nasopharyngeal carcinoma high‐risk families in Taiwan

Abstract

The utility of EBV load as a tumor marker in nasopharyngeal carcinoma (NPC) patients suggests that it might also serve as a screening test for individuals who are at high risk for developing NPC. We previously demonstrated that unaffected individuals from high-risk families had elevated anti-EBV antibody levels compared to community controls. In this study, we measured EBV load using 2 different real-time PCR assays (targeting BamH1W and polymerase gene sequences, respectively) carried out in 2 independent research labs in serum samples from 19 untreated NPC cases, 11 healthy community controls and 100 unaffected individuals from families in which 2 or more individuals were affected with NPC. EBV genomes were detectable in 68% of NPC cases by the EBV BamH1W assay and in 74% by the EBV polymerase assay (kappa = 0.64). Patients with stage III or IV disease had significantly higher EBV load compared to those with stage I or II disease (p = 0.008). EBV DNA was detected in a single community control sample by the EBV BamH1W assay and in none of the samples by the EBV polymerase assay. Only one of 100 unaffected family members tested positive by both assays. An additional 14 were positive by only one of the 2 EBV load assays used and usually in only one of the duplicate wells tested, all with very low viral loads (3-50 copies/ml). In addition, EBV load did not correlate with EBV serology results (anti-VCA, anti-DNase, anti-EBNA-1) among these unaffected family members. In conclusion, our study suggests limited clinical utility of the EBV load test, in its current configuration, to screen individuals from high-risk families. Should a more sensitive or specific molecular assay be developed that is capable of detecting and distinguishing tumor-derived EBV genomes or gene products from true negatives, it could be evaluated as a possible screening tool for asymptomatic and early-stage NPC.

Epstein‐Barr virus immune response in high‐risk nasopharyngeal carcinoma families in Greenland

“…Consistent with findings from Taiwan, EBV DNA in plasma was detected in similar frequencies of relatives and controls [Yang et al, 2006]. Thus, the presence of EBV in plasma is much less frequent in unaffected individuals at high risk of developing nasopharyngeal carcinoma than in nasopharyngeal carcinoma patients, which implies that the presence of EBV in plasma of nasopharyngeal carcinoma patients is the result of the tumor.…”

“…EBV DNA is detected in plasma in the majority (75-96%) of nasopharyngeal carcinoma patients from nasopharyngeal carcinoma high-incidence regions, and cell-free EBV DNA is used both as a marker for nasopharyngeal carcinoma detection and for monitoring the disease [Lo et al, 2000;Chan and Lo, 2002;Yang et al, 2006]. Consistent with findings from Taiwan, EBV DNA in plasma was detected in similar frequencies of relatives and controls [Yang et al, 2006].…”

Profiling of Epstein‐Barr virus‐encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs

“…43 But despite promising findings, Yang et al cautioned that the close association between plasma EBV DNA and the tumor might render it undetectable when identifying precursor lesions or early stages of NPC. 44 On the basis of independent studies quantifying plasma EBV DNA of primary NPC cases, 45 we found that some EBV microRNAs are present at comparable, if not higher copies and may be more readily detectable than EBV DNA under screening circumstances. Identifying EBV microRNAs more exclusive to NPC may also aid in screening against other EBV-associated malignancies that demonstrate elevated levels of circulating EBV DNA.…”

Systematic Review on Epstein-Barr Virus (EBV) DNA in Diagnosis of Nasopharyngeal Carcinoma in Asian Populations

“…Previous research has reported that cell-free EBV DNA can be quantitatively measured in the blood of NPC patients using polymerase chain reaction (PCR) technique Shotelersuk et al, 2000;Lin et al, 2001;Chan et al, 2003;Fan et al, 2004). Recent studies have demonstrated that the plasma EBV-DNA level might be a sensitive and reliable biomarker for the diagnosis of NPC at a molecular level/ clinical practice (Fan et al, 2004;Shao et al, 2004;Zhang et al, 2004;Yang et al, 2006). Samples which showed positivity for serum DNA were also positive for tissue DNA, which suggests that the serum EBV DNA originated from NPC and could be use as a marker for tumor DNA.…”