Human papillomavirus (HPV) has been largely demonstrated involved in the pathogenesis of several intraepithelial lesions and cancers. The role of HPV in the carcinogenesis of intraepithelial and invasive anogenital lesions is currently well established, characterized by integrated DNA HPV inside the lesions. HPV genotypes are classified according to their risk of oncogenesis and HPV16 remains the most common and higher oncogenic types. HIV-infected patients have a higher rate of HPV infection with a higher persistence and higher viral loads than general population, which can explain the increasing risk of cancers in such patients. However, independently of HIV infection, HPV infections seems to be strongly associated with several neoplasms, including head and neck, oral, cervical, anal, vulvar, vaginal cancers and probably some lung cancers. Paradoxically, little information about the immunity role and virological factors involved in the occurrence and outcome of HPV epithelial lesions are currently available, leading to more effective and biological approaches, in this HPV infection setting.