Epstein–Barr virus DNA level as a novel prognostic factor in nasopharyngeal carcinoma

Abstract

Background:The plasma Epstein–Barr virus (EBV) DNA level in patients with nasopharyngeal carcinoma (NPC) performs as an appealing prognostic factor, but conclusions of its prognostic values from previous studies are inconsistent. In this study, we performed a comprehensive meta-analysis to evaluate the prognostic value of EBV DNA level in patients with NPC.Methods:Published studies were searched in PubMed. The baseline characteristics of patients, overall survival (OS), and other survival outcomes were extracted. Pooled hazard ratio (HR), 95% confidence interval (CI), and P value were calculated to estimate the prognostic value of EBV DNA level. Each cut-off value mentioned in the studies was obtained. Kaplan–Meier curves were used to extract data, and graphical survival plots were extracted for calculating HR when the study did not describe the information directly.Results:This meta-analysis pooled 23 eligible studies including 10,732 patients with NPC. The pooled HR (95% CI) of pretreatment plasma EBV DNA level (pre-DNA) for OS was 2.78 (2.19, 3.55), and the HR (95% CI) of posttreatment plasma EBV DNA level (post-DNA) for OS was 5.43 (2.72, 10.82), suggesting that EBV DNA level was significantly correlated to the outcomes of patients with NPC.Conclusion:High expression levels of EBV DNA predicts poor prognosis in NPC.

Systematic comparison of plasma EBV DNA, anti‐EBV antibodies and miRNA levels for early detection and prognosis of nasopharyngeal carcinoma

“…In the EBV genome, there is only one copy of EBNA1 gene while BamHI‐W region may be reiterated by 7 to 11 repeats . Prevalent EBV in different populations may differ in the numbers of BamHI‐W region repeats, making prognostic cutoff value of pretreatment plasma BamHI‐W 76 bp level deduced from one cohort not optimal for another cohort . If plasma BamHI‐W 76 bp test results are intended to be used for prognosis, EBV DNA clearance rate calculated from pretreatment and posttreatment plasma EBV DNA load may be analyzed to rule out interindividual variability.…”

“…EBNA1 99 bp is a good prognostic marker regardless of early or late stages. [Color figure can be viewed at wileyonlinelibrary.com] pretreatment plasma BamHI-W 76 bp level deduced from one cohort not optimal for another cohort [42][43][44]. If plasma BamHI-W 76 bp test results are intended to be used for prognosis, EBV DNA clearance rate calculated from pretreatment and posttreatment plasma EBV DNA load may be analyzed to rule out interindividual variability.…”

The addition of pretreatment plasma Epstein–Barr virus DNA into the eighth edition of nasopharyngeal cancer TNM stage classification

“…9,[11][12][13][14][15]26 Two recent meta-analyses, with overlapping prospective and retrospective studies included in each respective meta-analysis, demonstrated that pretreatment plasma EBV DNA titer was a significant prognostic factor. 22,27 Different pretreatment cutoff values of the titers (including 1,500 copies per mL and 4,000 copies per mL in different studies) have been shown important. Nevertheless, almost all these trials as well as the meta-analyses were conducted using older editions of TNM stage groups and before the advent of IMRT.…”

“…We prespecified progression‐free survival (PFS), overall survival (OS) and cancer‐specific survival (CSS) as the most appropriate endpoints to evaluate the performance of the current and proposed stage groups on survival prediction . Local failure‐free survival, regional failure‐free survival and distant metastasis‐free survival have been reported as 3‐year endpoints in a previous publication …”

Impact of age on survival of locoregional nasopharyngeal carcinoma: An analysis of the Surveillance, Epidemiology, and End Results program database, 2004‐2013

“…EBV infection also contributes to pathogenesis of NPC via the Epstein‐Barr nuclear antigen 1 ( EBNA1 ), latent membrane protein 1 ( LMP1 ), LMP2 , and BamH1‐A fragment rightward reading frame 1 ( BARF1 ) genes (reviewed in Tsang et al, 2015 and Zhang et al, 2017). A growing body of evidence supports the hypothesis that activity of these and other genes in EBV‐positive patients with NPC results in substantially poorer outcomes in endemic as well as non‐endemic countries . Future studies of other cancer registries and databases in the US should be used to examine the relationship between HPV infection status, age, and race in more detail.…”