**2. A brief history of papillomavirus and cancer**

Human Papillomavirus infection was firstly identified from the embalmed body of a 12th century B.C. ancient Egyptian worker [2]. During the mummy necropsy procedure Scientists observed a wart on the sole of his foot. This evidences demonstrated that HPV infection occurred [3]. Medical literary tidings regard skin and genital warts were described in classical Greek and Roman literature [2]. However, association between viral origin of warts and sexual transmission was only confirmed in 19th century [2]. Rigoni-Stern (1842) hypothesized that cervical cancer could be promoted through sexual contacts. The Italian physician postulated this conception through the observation of high rates on cervical cancer in sexually active women, in comparison with non-sexually active women. [4]. Essays to establish relationship between cervical cancer and HPV-infections were initiated in 1972, this hypothesis was supported by a rare description of condylomata acuminate malignant transformation into squamous cell carcinomas highlighting the carcinogenic potential of hpv [4]. Harald zur Hausen, in 1975 [5], published that HPV could have a pivotal role in human cervix carcino‐ genesis. Eight year after, Hausen et al. identified the subtypes HPV16 and 18 on cervix cancer.

HPV infection was well established as etiologic factor of almost 100% of cervical malignancies [6]. After this appointment, several studies have addressed to find presence and prevalence of HPV infection in different tumor sites, including skin, urethra, nasal cavity, paranasal sinus, larynx, tracheobronchial mucosa and oral cavity [7]. In 1983, a series of studies presented by Syrjänen et al. [8] highlighted the possible correlation between HPV and oral lesions (nonneoplastic, benignant and malignant lesions). At the same year, a light microcopy study provided by Syrjänen et al. [9-11] firstly suggested a link among HPV infection, HNSCC and OSCC, through the examination of 40 biopsy specimens. These authors described morpho‐ logical alterations caused by HPV infection in 16 cases; this observation gives supports to HPV involvement in the development of OSCC. However, the confirmatory evidence of HPV-DNA in the oral lesions was presented only in 1985 [6,12]. Although the presence of HPV DNA has been suggested as a possible etiologic factor of oral pre-cancer and cancer, this association has not been as reliable as in cervical cancers.
