HPV vaccine is an exciting promise of the preventive medicine. Although HPV-immunization programs still reveal a number of unanswered questions, they represent a novel opportunity for primary prevention against cervical cancer and other HPV-related pre-neoplastic and neoplastic diseases. It is reasonable that the short and long-term benefits of vaccination on cervical and vulvo-vaginal HPV-related pathology will emerge when assuring over time a clear and complete information to the community and harmonizing the prevention strategies. Indeed, HPV-vaccination programs will require an understanding of new paradigms of infection and cancer control, and thus will require a rationale integration with the currently operating screening systems.