Comparison of plasma Epstein–Barr virus (EBV) DNA levels and serum EBV immunoglobulin A/virus capsid antigen antibody titers in patients with nasopharyngeal carcinoma

Abstract

BACKGROUNDSerologic measurement of antibodies to Epstein–Barr virus (EBV) immunoglobulin A/viral capsid antigen (IgA/VCA) and early antigen (IgA/EA) has been used widely to screen for nasopharyngeal carcinoma (NPC) in China. Recently, it was found that plasma EBV DNA concentration is an indicator for the staging and prognosis of patients with NPC. To determine whether there is a correlation between plasma EBV DNA levels and serum levels of IgA/VCA, the authors measured both in patients with NPC and in a control group.METHODSReal‐time polymerase chain reaction was used for quantitative analysis of plasma EBV DNA concentration, and enzyme‐linked immunoadsorbent assay was used to measure EBV VCA/IgA in patients with primary NPC (n = 120 patients), locally recurrent NPC (n = 8 patients), and distant metastatic NPC (n = 21 patients) among 76 patients with NPC after the completion of radiotherapy, in 60 patients with NPC in clinical remission, in 38 patients with non‐NPC tumors, and in 47 control individuals.RESULTSThe median plasma EBV DNA levels were 6200 copies/mL, 9200 copies/mL, and 2050 copies/mL in patients with primary, locally recurrent, and distant metastatic NPC, respectively, but declined to 0 copies/mL in patients with clinically remissive NPC, in patients who completed radiotherapy, in patients with non‐NPC tumors, and in the control group. In contrast, EBV VCA/IgA titers and detection rates remained high in all NPC groups. Plasma EBV DNA levels were significantly higher in patients who had serum VCA/IgA titers ≥ 1:640 (median, 83,450 copies/mL) compared with the levels in patients who had titers ≤ 1:320 (median, 17,200 copies/mL). Patients with NPC who had advanced TNM stage (Stages III and IV; median, 8530 copies/mL) and T classification (T3 and T4 tumors; median, 8530 copies/mL) had significantly higher plasma EBV DNA levels compared with patients who had early TNM stage (Stages I and II; median, 930 copies/mL) and T classification (T1 and T2 tumors; median, 3700 copies). Patients who had advanced TNM stage NPC had significantly higher mean VCA/IgA titers (1:424) compared with patients who had early TNM stage NPC (1:246), but there was no correlation between IgA/VCA titer and T or N classification of NPC.CONCLUSIONSThe results suggest that plasma EBV DNA detection is a more sensitive and specific marker than the serum IgA/VCA titer for the diagnosis and monitoring of patients with NPC. These findings provide convincing evidence for the use of plasma EBV DNA measurements for the early diagnosis and staging of NPC as well as for monitoring recurrence and metastasis of this tumor. Cancer 2004. © 2004 American Cancer Society.

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.…”

Plasma Epstein-Barr virus DNA level strongly predicts survival in metastatic/recurrent nasopharyngeal carcinoma treated with palliative chemotherapy

“…Plasma DNA was extracted and subjected to a real-time quantitative PCR assay as described previously. 13 The real-time quantitative PCR system was developed for plasma EBV DNA detection toward the BamHI-W region. The system consisted of the amplification primers W-44F ( …”

“…Recently, several studies including our own data have shown that quantification of plasma Epstein-Barr virus (EBV) DNA by the real-time quantitative polymerase chain reaction (PCR) is a useful marker in the detection, monitoring, and prognostic prediction for nondisseminated NPC treated by radiotherapy. [9][10][11][12][13] However, data regarding utility of plasma EBV DNA in metastatic NPC are rare. To our knowledge, only 1 study has demonstrated the predictive and prognostic value of the clearance rates of plasma EBV DNA during the first month in metastatic/recurrent NPC.…”

Mitochondrial DNA somatic mutations are frequent in nasopharyngeal carcinoma

“…15 Epstein-Barr virus (EBV) infection, as well as chromosomal alterations and environmental factors are associated with NPC. [16][17][18] Our previous study revealed that a 4,981 bp deletion in mtDNA occurs with high frequency (93%) in NPC tumors. This alteration was also found more frequently in advanced stage NPC.…”