Prophylactic human papillomavirus (HPV) vaccines based on intramuscular injection of non-infectious L1 virus-like particles (VLPs) are undergoing intense clinical evaluation. As documented in preceding chapters of this monograph, clinical trials of these vaccines have demonstrated their safety and high efficacy at preventing type-specific persistent cervical HPV infection and the development of type-specific cervical intraepithelial neoplasia (CIN) cervical neoplasia. There is widespread optimism that VLP vaccines will become commercially available within the next few years. The prospects for development of alternative HPV vaccines must be considered in light of the likelihood that a safe and effective prophylactic HPV vaccine will soon be available. Three questions need to be addressed: (1) Is there sufficient need for a second generation vaccine? (2) Are there sufficiently attractive candidates for clinical trials? (3) Is there a realistic development/commercialization path?