The emerging role of human cytomegalovirus infection in human carcinogenesis: a review of current evidence and potential therapeutic implications

It is well-established that infections with viruses harboring oncogenic potential increase the cancer risk. Virus induced oncogenic processes are influenced by a complex and unique combination of host and environmental risk factors that are currently not fully understood. Many of the oncogenic viruses exhibit a prolonged, asymptomatic latency after a primary infection, and cause cancer in only a minority of carriers. From an epidemiologic point of view, it is therefore difficult to determine their role in cancer development. However, recent evidence suggests a neoplastic potential of one additional ubiquitous virus; human Cytomegalovirus (HCMV). Emerging data presents HCMV as a plausible cancer-causing virus by demonstrating its presence in >90% of common tumor types, while being absent in normal tissue surrounding the tumor. HCMV targets many cell types in tumor tissues, and can cause all the ten proposed hallmarks of cancer. This virus exhibits cellular tumor-promoting and immune-evasive strategies, hijacks proangiogenic and anti-apoptotic mechanisms and induces immunosuppressive effects in the tumor micro-environment. Recognizing new cancer-causing mechanisms may increase the therapeutic potential and prophylactic options for virus associated cancer forms. Such approaches could limit viral spread, and promote anti-viral and immune controlling strategies if given as add on to standard therapy to potentially improve the prognosis of cancer patients. This review will focus on HCMV-related onco-viral mechanisms and the potential of HCMV as a new therapeutic target in HCMV positive cancer forms.