Role of herpes simplex type 2 in genital cancers: Review of the evidence

Human papillomaviruses (HPV) are strongly associated with pre-cancerous and cancerous lesions of the uterine cervix. However, the high rate of HPV infection in sexually active individuals and the long latency period before cancer, suggest that interactions of HPV with cofactors are required for progression towards malignant disease. Herpes simplex virus type 2 (HSV-2) had been proposed initially as a potential agent involved in cervical cancer. In vitro, HSV-2 DNA is capable of transforming immortalized rodent cells. Cooperation between oncogenic HPV types and HSV-2 DNA leads to the tumorigenic transformation of human epithelial cells. Seroepidemiological studies have yielded conflicting results on the role of HSV-2 in genital cancers. Using the polymerase chain reaction, HSV-2 transforming fragment Bgl II N has been detected in pre-cancerous and cancerous lesions of the uterine cervix, often in the presence of HPV infection. Since only a proportion of lesions contain HSV-2 DNA, this agent may act early in the oncogenic process and not be retained in cells throughout the process. PCR assays for specific transforming regions of HSV-2 need to be developed and applied on cohorts of individuals to assess the role of HSV-2 in the development of malignant lesions.