Cervical cancer and other HPV-associated cancers comprise an important public health burden worldwide, with over 600,000 HPV-associated cancers diagnosed each year. Prophylactic human papillomavirus (HPV) vaccination with three doses of commercially available vaccines, the regimen currently approved by the FDA, is highly efficacious in preventing targeted carcinogenic HPV infections and related cervical cancer precursors. In some regions of the world, two-dose vaccination schedules for adolescents have started to be recommended, based on immunobridging studies demonstrating immunologic non-inferiority of two doses in that age group, compared with three doses of the vaccine in the adult women in the phase III efficacy trials. Still, the majority of women who are at the greatest lifetime risk for cervical cancer are not being vaccinated because cost and logistical considerations for administering multi-dose vaccine programs continue to impede progress in reducing this preventable cancer.