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Review
. 2021 Apr 8;13(8):1785.
doi: 10.3390/cancers13081785.

The Incidence of Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis

Jisun Hwang  1 , Chong Hyun Suh  2 , Kyung Won Kim  2 , Ho Sung Kim  2 , Philippe Armand  3 , Raymond Y Huang  4 , Jeffrey P Guenette  4
Affiliations
Review

The Incidence of Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis

Jisun Hwang et al. Cancers (Basel). .

Abstract

The worldwide prevalence of Epstein-Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL) is undetermined. There is no clearly defined cut-off for EBV-encoded RNA (EBER) positivity in tumor cells by in-situ hybridization. The purpose of this study was to establish the proportions of EBV+ DLBCL patients and influence of the different cut-offs for EBER positivity, geographical location, and age on the prevalence of EBV+ DLBCL. PubMed and EMBASE were searched for studies published up to May 28, 2020 that reported proportions of EBER positivity in immunocompetent and de novo DLBCL patients. The pooled proportions were computed by an inverse variance method for calculating the weights and the DerSimonian-Laird method. Multiple subgroup analyses were conducted to explore any heterogeneity. Thirty-one studies (8249 patients) were included. The pooled proportion of EBV+ DLBCL was 7.9% (95% CI, 6.2-10.0%) with significant heterogeneity among studies (p < 0.001). The prevalence of EBV+ DLBCL was significantly higher in Asia and South America compared with Western countries (p < 0.01). The cut-offs for EBER positivity (10%, 20%, 50%) and patients' age (≥50 years vs. <50 years) did not significantly affect the prevalence (p ≥ 0.10). EBV+ DLBCL is rare with a pooled proportion of 7.9% in patients with DLBCL and the geographic heterogeneity was confirmed.

Keywords: immunohistochemistry; in situ hybridization; lymphoma; meta-analysis; systematic review.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of the included studies.
Figure 2
Figure 2
Forest plots of the pooled proportion of Epstein-Barr virus-positive (EBV+) diffuse large B cell lymphoma (DLBCL) in the included studies (n = 31).
Figure 3
Figure 3
Funnel plot of the proportion of EBV+ DLBCL in the included studies. Note the absence of funnel plot asymmetry.
Figure 4
Figure 4
(A–C) Forest plots of the pooled proportions of EBER positive DLBCL. Subgroup analyses were according to race (Asia and South America vs. Western countries) (A), cut-offs for EBER positivity (10%, 20%, 50%) (B), and patients’ age (elderly ≥50 years vs. young <50 years) (C).
Figure 4
Figure 4
(A–C) Forest plots of the pooled proportions of EBER positive DLBCL. Subgroup analyses were according to race (Asia and South America vs. Western countries) (A), cut-offs for EBER positivity (10%, 20%, 50%) (B), and patients’ age (elderly ≥50 years vs. young <50 years) (C).
Figure 4
Figure 4
(A–C) Forest plots of the pooled proportions of EBER positive DLBCL. Subgroup analyses were according to race (Asia and South America vs. Western countries) (A), cut-offs for EBER positivity (10%, 20%, 50%) (B), and patients’ age (elderly ≥50 years vs. young <50 years) (C).
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