A new treatment under development aims to prevent and cure squamous cell skin cancers by targeting the human papilloma virus (HPV). Researchers hope to receive clearance to begin testing the approach in human clinical trials in Australia during the second half of 2009.

Ian Frazer, who led research to deliver a vaccine for HPV-related cervical cancer, outlined the new work at a November conference in Brisbane, Australia.

The cervical cancer vaccine, commercialized by Merck and GlaxoSmithKline, protects against HPV strains 6, 11, 16 and 18. The new skin cancer research focuses on HPV strains 5 and 8, which have been associated with squamous cell carcinoma for at least 30 years (Proc. Natl. Acad. Sci. USA 75, 1537–1541, 1978; Bull. Cancer 65, 151–164; 1978.).

Unwelcome guest: HPV wreaks havoc Credit: Newscom

Frazer, director of the Diamantina Institute for Cancer, Immunology and Metabolic Medicine at the University of Queensland, acknowledges uncertainty over links between skin cancer and HPV strains carried by most humans. “There are people in the scientific community who believe that virtually no skin cancers are caused by papilloma viruses and others who believe that virtually all skin cancers are caused by papilloma viruses,” he says.

But he adds that “a very large number of papilloma viruses infect normal healthy skin at a low level—we don't know whether they are passengers that don't cause any problems or whether they do cause problems.” Frazer explains that HPV strains 5 and 8 are associated with the development of skin cancers in people with immune systems weakened by chemotherapy, transplant medication or other causes. These HPV strains are far less likely to occur in skin cancers in otherwise healthy individuals.

The attempt to target HPV in skin to prevent cancer breaks new ground, says virologist Arno Mullbacher of the John Curtin School of Medical Research at the Australian National University. However, Mullbacher cautions that immune interventions using vaccines as tools have generally achieved very low success rates.

Frazer, who is preparing to apply to the University of Queensland's ethics committee to conduct phase 1 human trials, believes this is the first attempt to tackle skin cancer by targeting its HPV links. (He is wary of raising hopes for the 'immunotherapeutic' treatment, which he estimates could require at least a decade to develop.) Vaccine and adjuvant components will support a biopharmaceutical element that temporarily enables antigen-specific T cells to kill skin cells with HPV-specific antigen markers.

The treatment is designed to stimulate T cells to attack skin cells that have turned cancerous or that are infected with HPV. If it works, it might initially be given to patients whose immune systems are due to be challenged by chemotherapy or other medications, reducing their risk of squamous cell cancer by clearing the HPV strains from their skin.

Frazer says animal studies conducted by his team have suggested that targeting HPV-infected skin might work (J. Natl. Cancer Inst. 96, 1611–1619; 2004). A key challenge going forward, however, is to ensure that the treatment does not expose healthy skin to T cell attack.