Antiviral approaches for cancers related to Epstein-Barr virus and human papillomavirus.

Epstein-Barr virus and human papillomaviruses (HPV) are DNA viruses underlying the carcinogenesis of 15-20% of human cancers worldwide. Viral oncoproteins are involved in malignant transformation and maintenance of the malignant phenotype, mainly through interaction between oncoproteins and products of tumour-suppressor genes. The use of vaccines to prevent the occurrence of HPV-related cancers is being investigated. Several approaches have been used to inhibit expression of viral oncoproteins. The first strategy uses antisense oligodeoxynucleotides against viral oncoproteins; downregulation of the oncoproteins can influence tumour cell growth and restore sensitivity to cytotoxic agents. Another approach uses antiviral drugs such as acyclic nucleoside phosphonates; inhibition of virus replication can lead to downregulation of viral oncoproteinsand ultimately reactivate tumour-suppressor-gene pathways. In addition, the combination of acyclic nucleoside phosphonates with conventional cytotoxic agents is more effective than either agent alone. These data provide the basis for a novel anticancer strategy to improve the therapeutic ratio in virus-related cancers, which needs to be further investigated for clinical applications.