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.
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 now-preventable cancer.
The Costa Rica Vaccine Trial (CVT) and the PApilloma TRIal against Cancer In young Adults (PATRICIA Trial), both of which tested the bivalent HPV vaccine, showed similar vaccine efficacy over four years among women who received one, two and three doses of the HPV16/18 vaccine. Stable antibody responses have been observed throughout the seven years of follow-up accrued to date in CVT, suggesting durability of responses. For the quadrivalent HPV, 36-month preliminary analysis of a large, post-licensure trial in India showed similar protection against HPV16/18 cervical infection whether the women received one dose, two doses, or three doses. However, vaccine recipients in these trials were not randomized to receive these fewer doses, and immunogenicity among one-dose recipients was lower than that observed following two- or three-doses. Thus, the level of evidence in support of single-dose HPV vaccination is insufficient to warrant changes in current recommendations for two- or three-dose schedules.
Reduced-dose schedules for prophylactic HPV vaccines will be discussed, as will the need for additional research, such as a direct evaluation of one-dose efficacy of the HPV vaccines.