Even if E6 and E7 are the viral early proteins playing the main oncogenic role [2,3], the evidence of HPV-associated cancers containing a mixture of integrate/episomal forms or exclusively episomes of HPV [4,5,6], where the expression of E5 is maintained [7,8,9], have suggested that a more relevant function in carcinogenesis could be played also by other early proteins, including E5 [10]. Here, ARHGEF15 is linked to cancer.