Long-term efficacy of human papillomavirus vaccination

Achieving long-term protection following vaccination is crucial to ensuring that high levels of immunity are maintained within a population while eliminating the need to introduce booster vaccinations. Based on an analysis of the hepatitis B virus vaccine, several factors have been shown to contribute to long-term protection, namely: specific lymphoproliferation, the in vivo humoral response, and immune memory. To ensure protection against persistent human papillomavirus (HPV) infection and the subsequent development of cervical lesions, an effective HPV vaccine must be able to induce strong humoral immune responses. Mathematical modeling analyses based on a three-dose regimen of HPV type 16 prophylactic vaccine indicated that 99% of 16- to 23-year-old women would have almost life-long detectable anti-HPV-16 levels. Available data on the quadrivalent HPV vaccine demonstrated that long-term immune memory was induced, with anti-HPV geometric mean titers after 5 years remaining at or above those observed with natural infection. Vaccination also resulted in a substantial reduction in the combined incidence of HPV-6/11/16/18 related persistent infection or disease, and there were no cases of precancerous cervical dysplasia compared with six cases in women receiving placebo. Similarly the bivalent HPV vaccine has been shown to induce long-term immunity with >98% seropositivity maintained after 4.5 years of follow-up and geometric mean titres at this time point remaining substantially higher than those noted with naturally acquired infection. Countrywide registration regarding population and health events in a stable population of approximately 25 million makes the Nordic countries an ideal setting for the evaluation of long-term cervical cancer control. Population-based long-term efficacy trials conducted in these countries aim to investigate the long-term efficacy of HPV vaccination with regard to invasive cervical cancer, and the results of these trials are awaited with interest.