High pretreatment plasma Epstein-Barr virus (EBV) DNA level is a poor prognostic marker in HIV-associated, EBV-negative diffuse large B-cell lymphoma in Malawi

Cancer Med. 2020 Jan;9(2):552-561. doi: 10.1002/cam4.2710. Epub 2019 Nov 29.


Plasma Epstein-Barr virus (EBV) DNA measurement has established prognostic utility in EBV-driven lymphomas, where it serves as a circulating tumor DNA marker. The value of plasma EBV measurement may be amplified in sub-Saharan Africa (SSA), where advanced imaging and molecular technologies for risk stratification are not typically available. However, its utility in diffuse large B-cell lymphoma (DLBCL) is less certain, given that only a subset of DLBCLs are EBV-positive. To explore this possibility, we measured plasma EBV DNA at diagnosis in a cohort of patients with DLBCL in Malawi. High plasma EBV DNA at diagnosis (≥3.0 log10 copies/mL) was associated with decreased overall survival (OS) (P = .048). When stratified by HIV status, the prognostic utility of baseline plasma EBV DNA level was restricted to HIV-positive patients. Unexpectedly, most HIV-positive patients with high plasma EBV DNA at diagnosis had EBV-negative lymphomas, as confirmed by multiple methods. Even in these HIV-positive patients with EBV-negative DLBCL, high plasma EBV DNA remained associated with shorter OS (P = .014). These results suggest that EBV reactivation in nontumor cells is a poor prognostic finding even in HIV-positive patients with convincingly EBV-negative DLBCL, extending the potential utility of EBV measurement as a valuable and implementable prognostic marker in SSA.

Keywords: Epstein-Barr virus; HIV; diffuse large B-cell lymphoma; prognosis; sub-Saharan Africa.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood*
  • DNA, Viral / blood*
  • DNA, Viral / genetics
  • Epstein-Barr Virus Infections / blood
  • Epstein-Barr Virus Infections / complications*
  • Epstein-Barr Virus Infections / diagnosis
  • Epstein-Barr Virus Infections / virology
  • Female
  • Follow-Up Studies
  • HIV / isolation & purification
  • HIV Infections / blood
  • HIV Infections / complications*
  • HIV Infections / diagnosis
  • HIV Infections / virology
  • Herpesvirus 4, Human / genetics*
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Lymphoma, AIDS-Related / blood
  • Lymphoma, AIDS-Related / epidemiology
  • Lymphoma, AIDS-Related / mortality*
  • Lymphoma, AIDS-Related / virology
  • Lymphoma, Large B-Cell, Diffuse / blood
  • Lymphoma, Large B-Cell, Diffuse / epidemiology
  • Lymphoma, Large B-Cell, Diffuse / mortality*
  • Lymphoma, Large B-Cell, Diffuse / virology
  • Malawi / epidemiology
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Survival Rate
  • Young Adult


  • Biomarkers, Tumor
  • DNA, Viral