**9. The HPV therapeutic vaccines and its perspectives**

Immunotherapy offers an attractive alternative treatment strategy because it can address both the underlying HPV infection and the visible lesions. Moreover, immunotherapy can target all HPV-associated lesions, regardless of location, and induce long-lasting immunity, thus preventing recurrence (Chu, 2003; Stanley, 2012).

A judgment of whether therapeutic HPV vaccine candidates have a real effect on disease has been difficult because most trials have not been placebo-controlled, and more important, it stills not clear for how long these patients can maintain high levels of immune response, as they have been already infected. The vaccines have also shown, at best, limited efficacy in eradicating established tumors, although the fact that they have mostly been tested in ad‐ vanced stage cancer patients with compromised immune systems may have limited their impact (Brinkman et al., 2005).

Perhaps the ideal HPV vaccine strategy calls for a vaccine that possesses both prophylactic and therapeutic properties. A chimeric vaccine of this type could both prevent new HPV infections and clear existing infections. Moreover, such a vaccine would benefit and could be administered to both sexually inexperienced young individuals and older individuals who already harbor HPV (Franceschi, 2005). Of course the costs of the rise of individuals been vaccinated needs to be estimated, in order to not turn HPV vaccine in an expensive waste of health budget. It is important to remember that although some groups are in risk group, not all individuals of this risk group will develop an HPV-related cancer. So, before implementing HPV vaccination to a wide range of patients, it needs to be better classified what populations should be included in vaccination process, and further develop new guidelines to better incorporate in this vaccination individuals that, even in risk groups, still have a higher risk in HPV-infection and spread. Opportunities for primary and secondary prevention should be assessed, including the use of HPV vaccines to prevent infection and therapeutic vaccines in the adjuvant setting for locoregional recurrence and distant disease (Marur et al. 2010). Combined with the fact that no therapeutic vaccines currently exist for other diseases, this goal makes therapeutic HPV vaccine development a challenging task.

The most recent report from Quadrivalent Human Papillomavirus Vaccine (HPV4) presents important facts about immunization practices, and provides excellent results. The efficacy for prevention of HPV 6-, 11-, 16- and 18-related genital warts was 89.3%, as a profilatic vaccine from those who have take 3 doses and was seronegative at day 1. From males who have received only one dose, regardless of serology or previous infection was of 68.1%. This efficacy was also confirmed by several other trials in female patients, with >98% efficacy in preventing HPV 6-, 11-, 16- and 18-related grade 2 or 3 cervical intraepithelial neoplasia or adenocarcinoma *in situ* (CDC MMWR, 2011).
