Impact of prophylactic HPV vaccination on the cervical cancer incidence and mortality . Perspectives for development of therapeutic HPV vaccines

In this Chapter we will discuss the current status of the prophylactic HPV vaccination, the introduction of HPV prophylactic vaccination and its impact on the cervical cancer incidence and mortality, challenges of the HPV vaccination in the developing world, screening post vaccination and the secondgeneration HPV prophylactic vaccines, as well as, the development of new therapeutic vaccines and its use at different stage of the Cervical Cancer (CC). Two commercial vaccines against HPV (Gardasil® and Cervarix®) are currently in the market in many countries around the world. Both are produced Correspondence/Reprint request: Dr. Vicente Madrid-Marina, Instituto Nacional de Salud Pública,Av. Universidad 655, Santa María Ahuacatitlán, Cuernavaca, C.P.62100, Cuernavaca, México. E-mail: vmarina@insp.mx Vicente Madrid-Marina et al. 156 with recombinant technologies, consist of self-assembled ViralLike Particles, the socalled VLPs, and had shown high immunogenicity. More important, they had been found highly efficient in preventing persistent infections and lesions not only from the uterine cervix, but also from the anus, vagina, and vulva. The development of prophylactic HPV vaccines and proof of efficacy as described in this chapter represents a landmark in the field of preventive medicine. The challenge now is to implement use of these vaccines and in so doping to see a significant impact on incidence and death rates from CC. This needs to be most effectively achieved in resource-poor countries, where cancer rates are higher but obstacles to vaccine implementation will be greatest. Unfortunately, in a world of competing health-care priorities, having the means and know does not always translate into success. Even where HPV vaccine will be available, implementation needs to address some issues. Foremost is education, so that women and their daughters understand the potential benefit of primary prevention. Despite the success of screening, around 20% of women do not access screening for a variety of reasons, including socio-cultural barriers because some groups are socio-economically deprived women, those from ethnic minorities, and of course, there are anxious individuals who just cannot cope with the idea of cervical screening. Unhappily, HPV vaccines are very expensive, and unaffordable for many Public Health initiatives in developing countries. They include two types involved in cancer development (16 and 18), and so we can only expect a partial protection against cancer (70/100), making it necessary to implement novel strategies to detect precursor lesions and cancer in the post vaccination era. Strategies that include education and organized screening programs with detection of persistent infections should be implemented in developing countries if a reduction of cancer of the uterine cervix is expected next years. Ongoing trials will document the precise degree of cross-protection and influence on preventing high-grade cervical intraepithelial neoplasia (HG-CIN) caused by other HPV types. In order to increase the protection provided, vaccines that contain multiple high-risk HPV types and which could prevent 90% of cancer are being developed. Issues of stability and cost will continue to drive the testing and development of alternatives to VLPs for second-generation vaccines. Another aspect of vaccination requiring greater clarity over time will be the duration of protection. It will take 15-20 years before a vaccinated girl reaches an age when CC becomes a significant risk and by that time we need to know whether booster vaccination will be required. The current generation of vaccinations will prevent not more than 60% of CIN 3, so a considerable amount of HG-CIN will inevitably occur for many years to come. A therapeutic vaccine to treat a persistent HPV infection, or even CIN 2+, would be an important advance in reducing morbidity, but much progress is requires to achieve significant clinical efficacy at a level that can challenge current therapy.