**7. HPV vaccine**

acanthosis is not so prominent, and differently from warty carcinoma, there is no koilocytosis.

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

**Sarcomatoid carcinomas:** correspond to 1-3% of cases. Macroscopically, they are hemorrhagic and necrotic, or polypoid tumors. Microscopically, they can mimic several sarcomas, like leiomyosarcomas, osteosarcomas, or fibrosarcomas. They are observed as tumors with two different cellular presentations, with the presence of epithelial and spindle cells. They are typically located in glans, not in corpora cavernosa, and may present foci of associated penile intraepithelial neoplasia. Immunohistochemical stains with high-molecular-weight cytokera‐

Other mixed tumors are often rare, which makes very difficult to establish their relationship with HPV infection, and comprises several subtypes, such as Pseudohyperplastic Carcinoma,

As stated before, distinct pathological variants of PSCC are associated with an indolent behavior (eg, verrucous, warty and Buschke-Lowenstein condyloma) and other with more aggressive forms (eg, usual SCC, basaloid and papillary). For basaloid and warty carcinomas, the HPV-infections are present in 80-100% of all cases. It is important to remember that *in situ* SCC seems to be strongly related with HPV-infection (Kayes et al., 2007). Seems plausible then that HPV-infection is far more important as a co-factor that will prepare the soil for a neoplastic malignant transformation, due to the several pathways in which HPV-infection contributes. This is in accordance with the theory of two major pathways in penile cancer development, being one driven by factors such as poor hygiene, presence of phimosis, chronic inflammation, etc), and another one driven by high-risk HPV-infection (Rubin et al., 2001). As discussed above, this represents an astonishing opportunity for a new approach to prevent this disease, as HPV vaccination researches are under constant evolution. As a health problem, the prevention of HPV infection might be able to avoid the development of these subtypes of

Although there are not many studies investigating a prognostic role for HPV-infection in penile carcinomas, some studies maintain HPV as a controversial factor, in terms either of survival, or local metastasis, and lymph node involvement. From the three more important studies, it is still unknown if HPV alone may have an impact in penile cancer`s patients overall survival, as demonstrated in several other solid tumors, such those arising in oral cavity and oropharynx (Lont et al., 2006). In a study conducted by Cubilla et al. (2010), HPV-16 was the most prevalent genotype (72% of all cases), followed by HPV-6 (9%) and HPV-18 (6%). The 16 and 18 genotype (high-risk HPV types) were proposed to be associated with aggressive variants of penile tumors, and to be associated with a poorer outcome in these patients. In several studies, the role of HPV infection in penile cancer could only be observed by indirect means, as the observation that HPV-infected PSCCs were those with more aggressive subtypes, as basaloid and warty tumors. So, it is believed that HPV-infection, specially related to HPV-16 and -18,

HPV in men, if the current knowledge of HPV-driven malignancy is right.

**6. HPV-status impact on outcome in penile carcinomas**

They have an excellent prognosis with very infrequent metastasis.

Carcinoma Cunilatum and Pseudoglandular Carcinoma.

tins and p63.

In many countries, vaccines against some HPV types are administered to girls and young women with the goal of protecting them against HPV-induced cervical cancer (Villa et al., 2005; Muñoz et al., 2010). The introduction of HPV vaccines has also drawn more attention to the fact that HPV is associated not only with cervical cancer and genital warts but also with other tumors, such as head and neck and anogenital cancers (Zur Hausen, 2006).

Although the majority of HPV vaccine research has focused on cervical cancer, some vaccine developers have targeted other diseases related to different strains of HPV.

Emerging results from vaccine trials have suggested that some cross-protection is possible. Vaccines against cervical cancer also have the potential to prevent other cancers that are caused by the same types of HPV (Herrero et al., 2003, Kreimer et al., 2005), and half or more of anogenital cancers outside the cervix, including cancer of the vulva, vagina, penis, and anus (Daling et al., 2005, Gross & Pfister 2004). Theoretically, these vaccines should also work against the same viruses at other anatomical sites, which would be of great value for the majority of the patients. Since different HPV-related diseases have share the same contamination basis (eg, HPV contamination in sexual act may happen in anogenital, cervical and even in head and neck areas. Also, almost all HPV-related tumors share individual at risk with the same behavior, and it is believed that this prevent potential directed to several organs could reduce the prevalence of several tumors simultaneously. If proven to do so, this approach would represent a major conceptual breakthrough, not only in prevention of these diseases, but equally importantly, by providing the 'missing link' in the chain of evidence for the final proof of HPV etiology in these tumors (Syrjänen, 2010).
