Genital human papillomaviruses – current and prospective therapies

HPV Infection with human papillomaviruses is very common and associated with benign and malignant epithelial proliferations of skin and internal squamous mucosae. A subset of the mucosal HPVs are oncogenic and associated with 5% of all cancers in men and women. There two licensed prophylactic vaccines, both target HPV 16 and 18, the two most pathogenic, oncogenic types and one, additionally, targets HPV 6 and 11 the cause of genital warts.

The approach of deliberate immunisation with oncogenic HPV E6 and/or E7 proteins and the generation of antigen specific cytotoxic T cells as an immunotherapy for HPV associated cancer and their high grade precancers has been tested with a wide array of potential vaccine delivery systems in Phase I/II trials with varying success. Understanding local viral and tumour immune evasion strategies is a prerequisite for the rational design of therapeutic vaccines for HPV associated infection and disease, progress in this is discussed. There are no anti-viral drugs for the treatment of HPV infection and disease.

Current therapies are not targeted anti-viral therapies but either attempt physical removal of the lesion or induce inflammation and a bystander immune response. There has been recent progress in the identification and characterisation of molecular targets for small molecule antagonists of the HPV proteins E1, E2 and E6 or their interactions with their cellular targets. Lead compounds that could disrupt E1:E2 protein/protein interactions have been discovered as have inhibitors of E6:E6-AP binding interactions. Some of these compounds showed nanomolar affinities and high specificities and demonstrate the feasibility of this approach for HPV infections. These studies are, however at early phase, and it is unlikely that any specific anti-HPV chemotherapeutic will be in the clinic within 10-20 years.


Genital human papillomaviruses – current and prospective therapies. J Gen Virol. 8 Feb 2012

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