**6. HPV oncogenic potential**

HPV infection may lead to cell immortalization by means of infection of the mucosa and skin basal epithelial cells, which are the only ones that keep in the cell cycle [8, 61]. It may be by itself a causative agent of malignant transformation or when associated with other unclear cofactors [61]. However, some researchers have argued that HPV is not able to cause malignant transformation, despite the studies which point to the contrary [12].

Some factors should come into play to immortalize cells: virus type, synergetic action among physics, biological and chemical agents and genetic constitution, which are able to modify the natural course of the disease. But if the exposed person has a favorable condition and acquires high risk HPV it becomes easier to integrate viral DNA into human genome [61].

Oral HPV has been diagnosed in OSCC and it is believed that it has been involved in oral carcinogenesis by transforming the keratinocytes through a mechanism involving E6 and E7 proteins. However, the mechanisms behind immune response against high risk HPV remain unclear [67-69].
