Prevalence of Human Cytomegalovirus in Glioblastoma Multiforme: A Systematic Review and Meta-analysis
Francisco Cezar Aquino de Moraes1, Pedro Bartkevitch Rodrigues2, Lucas David de Souza Vital3, Barbara Antonia Talah4, Mario Hiroyuki Hirata1
1Department of Clinical and Toxicological Analysis, University of São Paulo, 2Department of Neurosurgery, University of Miami, 3Department of Medicine, Federal University of Amazonas, 4Pontifical Catholic University of Paraná
Objective:
Determine the global prevalence of Human Cytomegalovirus (HCMV) in glioblastoma and assess how regional, socioeconomic, and methodological factors influence detection rates.
Background:
Human cytomegalovirus (HCMV) is implicated in glioblastoma through oncogenic and immunomodulatory mechanisms, yet prevalence estimates remain highly variable, warranting systematic evaluation.
Design/Methods:

We systematically searched PubMed, Embase, and Cochrane for studies on HCMV detection in glioblastoma. A single-arm meta-analysis estimated pooled prevalence with subgroup analyses by region, country, income level, antibody, and detection method. Random-effects models (95% CI) were applied, and heterogeneity quantified using I².

Results:

19 studies comprising 988 glioblastoma patients were included, HCMV positivity was 68% (95% CI, 0.53 to 0.80; P < 0.0001; I² = 91.4%). Subgroup analyses revealed a significant prevalence in Europe and Central Asia (82%; 95% CI, 0.63 to 0.93; P < 0.0001; I² = 94.7%) and North America (78%; 95% CI, 0.23 to 0.98; P < 0.0001; I² = 94.3%), followed by Middle East/North Africa (72%; 95% CI, 0.45 to 0.89; P < 0.0001; I² = 87.4%), Latin America and Caribbean (65%; 95% CI, 0.25 to 0.91; P < 0.0001; I² = 85.5%), and East Asia and Pacific 0.51 (95% CI, 0.16 to 0.86; P < 0.0001; I² = 94.6%). High-income and upper-middle-income countries have a predominance of 69% and 70% (95% CI, 0.42 to 0.88 and 0.52 to 0.87, P < 0.0001, I² = 95.2% and 83.5%) compared to lower-middle-income (53%; 95% CI, 0.25 to 0.79; P = 0.0012; I² = 90.4%). Detection methods influenced prevalence, with IHC showing 76% positivity versus 65% ELISA and 66% PCR. Antibody analysis highlighted the significance of UL83 (95%) and IE-73 (87%) within studies.

Conclusions:

This meta-analysis revealed high HCMV detection in glioblastoma, although results vary by region, income, technique, and antibody. Standardized protocols and large studies are needed to clarify HCMV's role and implications for targeted therapies.

10.1212/WNL.0000000000216470
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