The human papillomaviruses (HPVs) are a diverse group of infectious agents, some of which are a causative agent of human cancers. Cervical cancer and oral cancer are closely associated with specific types of HPV, and the tumors grow only if there is continual expression of the viral E6 and E7 genes. Evidence from in vitro studies shows that when expression of these genes is inhibited by gene therapy approaches such as antisense RNA, ribozymes, or siRNA, the transformed phenotype of the cells is lost. Although it seems possible that clinical applications of this approach could help in the management of cervical and oral cancers there have been no clinical trials of gene therapy for HPV-associated cancers. Since the basic information is now available, a shift to translational research would be greatly welcomed.