Human cytomegalovirus seropositivity is associated with decreased survival in glioblastoma patients

Background Human cytomegalovirus (HCMV) is an oncomodulatory human herpesvirus that has been detected in glioblastoma (GBM) and is associated with worse prognosis in patients with the disease. The effects of HCMV systemic infection on survival in GBM patients, however, are largely unknown. We aimed to determine the association between HCMV serostatus at diagnosis and survival via a retrospective cohort study of GBM patients. Methods Plasma from 188 GBM patients treated at the Ben and Catherine Ivy Center (Seattle, WA) was tested for HCMV serostatus via enzyme-linked immunosorbent assays of anti-HCMV immunoglobulin (Ig)G. HCMV IgG serostatus was analyzed with respect to each patient's progression-free and overall survival (OS) via log-rank and multivariable Cox regression analysis. Results Ninety-seven of 188 (52%) patients were anti-HCMV IgG seropositive. Median OS was decreased in the IgG+ cohort (404 days) compared to IgG- patients (530 days; P = .0271). Among O6-methylguanine-DNA methyltransferase (MGMT) unmethylated patients (n = 96), median OS was significantly decreased in IgG+ patients (336 days) compared to IgG- patients (510 days; P = .0094). MGMT methylation was associated with improved OS in IgG+ patients versus those who were unmethylated (680 vs 336 days; P = .0096), whereas no such association was observed among IgG- patients. Conclusions In this study, HCMV seropositivity was significantly associated with poorer OS in GBM patients. This finding suggests prior infection with HCMV may play an important role in GBM patient outcomes, and anti-HCMV antibodies may, therefore, prove a valuable prognostic tool in the management of GBM patients.