Efficacy, duration of immunity and cross protection after HPV vaccination: a review of the evidence.

The efficacy and immunogenicity of HPV vaccines has proven excellent in several phase 2 and phase 3 trials involving tens of thousand women. A decrease in antibody titres was observed in follow-up studies of vaccinees, with initial sharp decline reaching a plateau in the longer term. Only few subjects lost their antibodies during the 5-6 years after vaccination. However, no breakthrough disease occurred even in those subjects. The administration of a challenge dose of quadrivalent vaccine at month 60 of follow-up resulted in a strong anamnestic response. The mechanism by which vaccination confers protection and the reasons for continuing vaccine efficacy remain to be elucidated. The same applies to the possibility of inducing an anamnestic response following viral challenge via genital mucosa. Data strongly suggest that both vaccines can have a variable level of cross protection against HPV types genetically and antigenically-closely related to vaccine types. Demonstration of cross protection against combined endpoints (CIN2/3 and AIS) for combined HPV types, and, as a single type, for HPV-31, has been reached for the quadrivalent vaccine, and there is evidence of cross protection against HPV 31 and 45 persistent infections (as single types) for the bivalent vaccine. Assays used for antibody detection were different for the two vaccines, and standardisation of methods for anti-HPV L1 protein detection is presently underway. The possibility to use universally accepted tests for antibody measurement would make comparison between vaccines and among different studies much easier.