Development of a topical protein therapeutic for human papillomavirus and associated cancers

Human papillomaviruses (HPVs) are the causative agents of several disease states, including genital warts and cervical cancer. There are around 500 million cases of genital warts per annum worldwide and around 450 000 cases of cervical cancer. Although HPV vaccines should eventually reduce the incidence of these diseases, new and effective treatments are still urgently required. The E2 (early) proteins from some HPV types induce growth arrest and apoptosis, and these proteins could be used as therapeutics for HPV-induced disease. A major obstacle to this approach concerns the delivery of the protein to HPV-transformed cells and/or HPV-infected cells in vivo. One possible solution is to use recombinant viruses to deliver E2. Another possible solution is to use purified E2 proteins or E2 fusion proteins. The herpes simplex virus VP22 protein is one of a small number of proteins that have been shown to cross the cell membrane with high efficiency. VP22-E2 fusion proteins produced in bacterial cells are able to enter mammalian cells and induce apoptosis. This suggests that VP22-E2 fusion proteins could be topically applied as a treatment for HPV-induced diseases, most probably post-surgery. In this review, we discuss this and other approaches to the topical delivery of selective therapeutic agents against HPV-associated conditions.