Presence of the Human Cytomegalovirus in Glioblastomas—A Systematic Review

SIMPLE SUMMARY: Whether the human cytomegalovirus (HCMV) is present in samples obtained from patients with glioblastoma (GBM) has been a matter under debate during the last two decades. Many investigators have demonstrated the presence of HCMV proteins and nucleic acids in GBM tumors, while some have not been able to detect it. It is important to evaluate current data and resolve these issues to clarify the possible role of the HCMV in GBM tumorigenesis and if this virus can serve as a potential target of therapy for these patients. In the present systematic review, we aim to review published research studies with a focus to identify differences and similarities in methods used for the detection of the HCMV in GBM samples found to be positive or negative for HCMV. Our data suggest that the HCMV is highly prevalent in glioblastomas and that optimized immunohistochemistry techniques are required to detect it. ABSTRACT: Glioblastoma is a malignant brain tumor with a dismal prognosis. The standard treatment has not changed in the past 15 years as clinical trials of new treatment protocols have failed. A high prevalence of the human cytomegalovirus (HCMV) in glioblastomas was first reported in 2002. The virus was found only in the tumor and not in the surrounding healthy brain tissue. Many groups have confirmed the presence of the HCMV in glioblastomas, but others could not. To resolve this discrepancy, we systematically reviewed 645 articles identified in different databases. Of these, 81 studies included results from 247 analyses of 9444 clinical samples (7024 tumor samples and 2420 blood samples) by different techniques, and 81 articles included 191 studies that identified the HCMV in 2529 tumor samples (36% of all tumor samples). HCMV proteins were often detected, whereas HCMV nucleic acids were not reliably detected by PCR methods. Optimized immunohistochemical techniques identified the virus in 1391 (84,2%) of 1653 samples. These data suggest that the HCMV is highly prevalent in glioblastomas and that optimized immunohistochemistry techniques are required to detect it.