**9. Final considerations**

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, to personalize the treatment for individual patients. However, for a better understanding about real therapeutic implications of HPV-status of tumors on OSCC clinical outcome, the next generation of clinical trials could be significantly improved and standardized in their design. According to exposed in the present issue, and defended by our research group and other authors [36-37], we believe that diagnosis strategy based in early detection in oral Pre-Cancerous lesions and OSCC reduces the treatment at the advanced stage, thereby increasing the cancer cure chances. Our group also believes that the increasing effects of HPV vaccination in several cancers could help to reduce the number of new HNSCC and OSCC cases. Although knowledge of the accurate effects of HPV vaccination on cancer incidence will probably continue for several years, monitoring the current effects of HPV vaccination is crucial, not only in cervical cancer, but also in HNSCC and OSCC.
