While many potential risk factors for brain cancer have been identified, including smoking and alcohol consumption, various pathogenic infections, including cytomegalovirus (CMV), may also constitute an under-appreciated but significant risk.
In 2011, there were an estimated 144,463 people living with brain and other nervous system cancers in the U.S. Glioblastoma (GBM) is considered the most common and most aggressive malignant primary brain tumor in humans, accounting for about 15 percent of all cases.
First described in 2002, the link between CMV and GBM has been championed by Dr. Charles Cobbs, a UCSF-trained neurosurgeon, who initially explored his hypothesis during off-hours and without formal research funding. Dr. Cobbs found that a high percentage of GBM tumors were infected with CMV; he also noted that the CMV virus resided in the tumor but not in the healthy tissue surrounding it.
A myriad of studies have since reinforced Dr. Cobbs’ findings. Using highly sensitive detection techniques, including PCR amplification, CMV nucleic acids and genes have been found in more than 90 percent of some GBM tumors.
Furthermore, a 2013 study found that CMV infection levels in GBM patients may predict survival. In that study, CMV infection was detected in 74 of 75 tumors – notably, prognosis differed based on the level of CMV infection – in patients with low-grade CMV infection, median survival was 20 months longer than in patients with high-grade infection. Presently there is no causal link between CMV infection and GBM development, though this research suggests that CMV may contribute to the progression of GBM.
In April 2011, oncologists and virologists involved in studying the relationship between CMV and GBM gathered in Washington, D.C. Based on published data, researchers concluded that CMV sequences and viral gene expression are present in most malignant brain tumors, and that CMV could modulate the progression of GBM by interacting with key signaling pathways. The researchers noted that future studies should focus on elucidating CMV’s role in tumor development.
At this time, it is unclear whether CMV plays an active role in glioblastoma progression or if it becomes reactivated under conditions that result in chronic inflammation or immunosuppression. GBMs are known to exert a variety immunosuppressive effects in patients, all of which could contribute to the establishment of environment that would permit CMV infection or reactivation at the tumor site.
Researchers are continuing to study the relationship between CMV, GBM, and other malignancies. Given that tumor-associated antigens are generally poorly immunogenic, there is growing interest in exploring vaccination against CMV antigens, which are highly immunogenic, as a component of new immunotherapeutic strategies against GBMs.