Human genital papillomaviruses are the necessary cause of cervical cancer. A prophylactic vaccine designed to prevent genital HPV disease by inducing virus neutralizing antibodies has been proposed. Studies on animal models have produced relevant data on the efficacy of HPV vaccine. The results of HPV clinical studies suggest that it will be possible to develop an effective vaccine. Nevertheless the number of subjects analyzed in the full text published clinical studies is still poor. Although a recently presented phase III study appears satisfied, it is probably necessary for a larger phase III study. Besides the choice of the geographical area for a very large clinical trial, there are different aspects to consider, such as the identification of the target population, identification of the endpoints, composition of the vaccine and marketing of the vaccine. Furthermore there are two open questions: the duration of protection and the behavioral modifications. All these issues are discussed in this review.