**Author details**

Prophylactic vaccines work primarily by inactivating HPV before the virus infects the host cells, stimulating humoral immunity [111]. Nowadays, there are two types of prophylactic HPV vaccine available in United States: the quadrivalent vaccine (Gardasil®) and bivalent vaccine (Cervarix®). The quadrivalent vaccine was first licensed for use in females to prevent cervical, vaginal and vulvar cancers and are effective against infection with HPV types 6, 11, 16 and 18 [112]. In 2009 the licensure was expanded to include males demonstrating effective‐ ness to prevent genital warts in both genders [113]. Bivalent vaccine was licensed for use in the U.S. in 2009 providing cervical cancers protection against HPV types 16 and 18 [114]. The impact of HPV prophylactic vaccination will address not only the incidence of cervical and anogenital cancers in women and men but also the incidence of some head and neck tumors. Growing number of head and neck cancers HPV-positive highlights the importance of routine prophylactic vaccination against HPV and, associated with alcohol and tobacco control, may

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

Also, therapeutic vaccines against HPV have to request cell mediated immunity and can also help prevent the progression of low-grade disease and lead existing lesions to regress, avoiding the recurrence of cancer lesions after treatment [116,117]. However, recent studies demon‐ strated the reduced effectiveness of therapeutic HPV-vaccine in established tumors. This could be explained by the fact that they have especially been tested in patients with compromised immune systems due advanced stage cancer [118]. A vaccine that possesses both prophylactic and therapeutic properties could be most effective HPV-vaccine strategy, preventing new and clear established HPV-infections. Additionally, the vaccine could be administered in, sexually inexperienced young individuals or older individuals HPV-infected, beneficiating them [119].

In recent decades, controversial results were not being able to provide the real role of HPV infection in OSCC genesis. An interesting fact that supports the controversial role of HPVinfection in OSCC is the highly fluctuating HPV-prevalence in comparison with cervical cancer. It may be due to HPV-detection influenced by: a reduced number of viral-copies, a viral-infection in a particular cell population, biopsy samples and detection methods (numer‐ ous methods and protocols for detection). Several details elucidating the relationship between pre-cancerous lesions, OSCC with HPV-infection must to be understood. The genomic detection of HPV-DNA, primarily in Pre-Cancerous lesions, provides stronger support for a viral etiology of HNSCC and OSCC. However the correlation between malignant transforma‐ tion of Pre-Cancerous lesions and HPV-infection were not completely elucidated. Recently, numerous studies have suggested that HPV-infection could play an important role in oral carcinogenesis through the Oral leukoplakia malignant transformation. Although some synergies between HPV oncogenes and other carcinogens have been hypothesized, some researchers have showed, specifically in oral mucosa, that positive HPV-infection in OSCC might not result from viral infection but rather from an incidental HPV colonization. In addition, targeted therapy for HNSCCs and OSCC currently request an increased number of predictive biomarkers, such as the HPV-infection status and mutation-status of crucial genes,

be crucial in head and neck cancer prevention [115].

**9. Final considerations**

Danilo Figueiredo Soave1\*, Mara Rubia Nunes Celes2 , João Paulo Oliveira-Costa3 , Giorgia Gobbi da Silveira3 , Bruna Riedo Zanetti3 , Lucinei Roberto Oliveira4 and Alfredo Ribeiro-Silva3

\*Address all correspondence to: dsoave@usp.br

