**10. Final considerations**

Gardasil for use in males aged 9–26 to prevent genital warts and to prevent the spread of cervical cancer. Moreover, the FDA (2010 and 2010a) has proclaimed that the dosing and administration schedule should be 0.5 mL administered intramuscularly (preferably in a deltoid muscle) on a 3-dose schedule. The second dose should be administered 1 to 2 months

Although clinical trials of Gardasil and Cervarix have been extremely promising, these first generation VLP vaccines may not be the ideal vaccine candidates, especially in already infected

The most recent report from Quadrivalent Human Papillomavirus Vaccine 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 con‐ firmed 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

Another important issue in vaccination process is to determine who are the individuals in more risk populations, in order to a better efficacy, and a reduction of the high costs involved in the vaccine production and distribution. Based on incidence of HPV-infection between several groups, the probabilities of being infected, especially subtypes 16 and 18, are higher in men who have sex with men (MSM) group than in heterosexual men (Heiligenberg, 2010). Several diseases have a higher incidence in MSM group, such as anal intraepithelial neoplasia (AIN), anal cancers, and genital warts (Jin et al., 2007). Another important group which might be benefited by HPV immunization is the HIV-positive patients, although it is not clear whether the immunization could provide a long time antibody titers against HPV 6, 11, 16, and 18, and how immunossupressed patients would react to HPV4 vaccine, in terms of safety and adversely reactions. However, as HPV4 is not a live vaccine, it can be safely administered to person in the most highly risk, such as immunocompromised individuals (like HIV-positive,

Researchers are now actively working to better develop prophylactic HPV vaccines that may

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

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

drug-driven immunossupression, or disease-related immunossupression).

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

preventing recurrence (Chu, 2003; Stanley, 2012).

be effective against a broader range of HPV types and have a longer shelf life.

later, and the third dose should be administered 6 months after the first dose.

232 Human Papillomavirus and Related Diseases – From Bench to Bedside A Diagnostic and Preventive Perspective

patients, and older men and women.

MMWR, 2011).

Several aspects still remain to be discovered in the field of penile cancers and HPV infection, and although last decade researches were not able to define a causal role for HPV-infection, several progresses have being made in this matter. The genomic detection of HPV DNA, primarily in some subtypes of PSCCs, provides stronger support for a viral etiology in this disease, and corroborates the idea that there are at leas 2 main pathways in penile carcino‐ genesis, and one of them is closely related to HPV.

Targeted therapy for PSCCs now demands more predictive biomarkers, such as the HPV infection status and mutation status of crucial genes, which could contribute to personalized treatment for each individual and decrease the inherent morbidities. However, for a better understanding of whether the HPV status of tumors has real therapeutic implications in affecting the clinical outcome, upcoming clinical trials should be significantly standardized in their design and performed on PSCC, which have been adequately selected and classified with respect to the different penile carcinoma subtypes. Moreover, we suggest that a more defined consensus in the histological classification in PSCCs should be utilized to improve HPV detection and provides means to compare studies in different populations. This is highly remarkable as is now fully accepted that penile carcinogenesis is quite dependent of local characteristics, and varies worldwide.

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Human Papillomavirus Infection and Penile Cancer: Past, Present and Future

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We believe that the increasing effects of HPV vaccination in several cancers could help to reduce the number of new PSCC cases, especially in developing countries, with a lower income, and less educated individuals. Although detection of the true effects of HPV vacci‐ nation on cancer incidence will probably continue for several decades, monitoring the current effects of HPV vaccination is crucial, not only in cervical cancer, but also in penile cancer.
