Michelle Giles and Suzanne M. Garland
from: Papillomavirus Research: From Natural History To Vaccines and Beyond (Edited by: M. Saveria Campo). Caister Academic Press, U.K. (2006)
Vaccines against human papillomavirus (HPV) may be prophylactic, therapeutic or a combination. Currently, prophylactic multivalent virus like particle (VLP) vaccines comprising the major capsid protein L1 are in Phase III clinical trials with preliminary results from Phase II trials indicating safety, plus 100% efficacy from persistent infection, as well as from infectious complications such as cervical dysplasia. The success of prophylactic vaccines is underpinned by their induction of neutralizing antibodies to the viral capsid, although we await long-term follow-up, to evaluate their prevention of neoplasia. Numerous therapeutic vaccines targeting nonstructural early viral antigens and including approaches such as peptide, viral-vector, DNA and dendritic cell vaccines are under investigation. Therapeutic vaccines are very much in their infancy compared with prophylactic vaccines, as although many show immunogenicity, this does not generally translate into reliable clinical responses. A number of these vaccines have been studied in phase I/II trials in humans, namely in women with cervical intraepithelial neoplasia (CIN), vulval intraepithelial neoplasia (VIN) and advanced cervical cancer. Although it is likely that a prophylactic vaccine will be licensed in the very near future, there are still many challenges to implementation of an effective HPV vaccine program, not the least of which will be cost effectiveness in setting where there are preventative screening programmes. Furthermore such challenges will differ from developed to developing countries. Challenges include unanswered questions such as the best age group to target, whether both genders should be vaccinated, the duration of efficacy, how vaccination will alter current recommendations for conventional cervical screening, whether there will be HPV genotype replacement, or genotype resistance, whether any cross protection will exist between genotypes, to how many genotypes can be placed in one vaccine. Of primary importance is whether the vaccine will be accessible and affordable to women in developing countries, where there is the greatest burden of HPV related disease. In addition, for successful vaccine implementation and uptake, there will need to be education of physicians, the general public, as well as those at government levels. The success of such vaccine programs will probably take many years to realize. Nevertheless, the prospect of a vaccine, which protects against the most common viral sexually transmitted infection and thereby protects against the complications of HPV infection such as cervical cancer, is extremely exciting. With current practices, the world projected rates of the burden of invasive cancer being over one million cases per year by 2050, primary prevention by the introduction of a successful HPV prophylactic vaccine should be one of the most significant public health initiatives of this decade read more ...