Cytomegalovirus infection may be oncoprotective against neoplasms of B-lymphocyte lineage: single-institution experience and survey of global evidence

Abstract

Background: Although cytomegalovirus (CMV) is not considered tumorigenic, there is evidence for its oncomodulatory effects and association with hematological neoplasms. Conversely, a number of experimental and clinical studies suggest its putative anti-tumour effect. We investigated the potential connection between chronic CMV infection in patients with B-lymphocyte (B-cell) malignancies in a retrospective single-center study and extracted relevant data on CMV prevalences and the incidences of B-cell cancers the world over.

Methods: In the clinical single-center study, prevalence of chronic CMV infection was compared between patients with B-cell leukemia/lymphoma and the healthy controls. Also, global data on CMV seroprevalences and the corresponding country-specific incidences of B- lineage neoplasms worldwide were investigated for potential correlations.

Results: Significantly higher CMV seropositivity was observed in control subjects than in patients with B-cell malignancies (p = 0.035). Moreover, an unexpected seroepidemiological evidence of highly significant inverse relationship between country-specific CMV prevalence and the annual incidence of B-cell neoplasms was noted across the populations worldwide (ρ = -0.625, p < 0.001).

Conclusions: We try to draw attention to an unreported interplay between CMV infection and B-cell lymphomagenesis in adults. A large-scale survey across > 70 countries disclosed a link between CMV and B-cell neoplasms. Our evidence hints at an antagonistic effect of chronic CMV infection against B-lymphoproliferation.

Keywords: B-cell malignancies; Cytomegalovirus; Global; Oncoprotection; Seroprevalence.

Fig. 1

The scatter charts present country specific CMV prevalence (mean) plotted against estimated age-standardized (world) annual incidence rates (per 100,000) of microscopically verified cases of B-cell types of cancer in 74 countries (blue circles) [35, 36, 69]. A) B-cell malignancies (all types) (Spearman ρ = -0.625, p < 0.001), B) Hodgkin’s disease (Spearman ρ = -0.618, p < 0.001), C) non-Hodgkin lymphomas (Spearman ρ =  = -0.617, p < 0.001), and D) multiple myeloma (Spearman ρ = -0.633, p < 0.001) in 2020. The inverse relationship between viral pervasiveness and the annual incidence rate of hematologic malignancies is highly significant for all (A) and each individual B-cell cancer type (C-D)