The long-term effect of two and three doses of bivalent HPV vaccination against HPV infections: a comparison between two observational cohort studies.

Abstract

We assessed long-term vaccine effectiveness (VE) of 2-dose and 3-dose bivalent HPV vaccination schedules in the Netherlands against incident and persistent HPV infections. Indirect effects of the 3-dose schedule were also assessed. Data from the longitudinal cohort studies HAVANA and HAVANA-2 were used. Women annually provided questionnaires and vaginal samples for HPV determination using the SPF10-DEIA-LiPA25-assay. VEs were assessed using Cox regression over 14 years (3-doses at age 14-16) and 9 years (2-doses at age 12). Changes in 3-dose VE estimates over time were tested. Indirect effects were calculated by comparing unvaccinated participants using Poisson and Cox regression. We included 1,665 HAVANA women and 2,441 HAVANA-2 women. VEs against incident HPV16 and HPV18 infections for 3-doses were 74.3% (95%CI: 56.0-85.0%) and 85.0% (76.1-90.6%) up to 14 years, respectively, and for 2-doses 86.6% (61.6-95.4%) and 95.9% (69.3-99.4%) up to 9 years. For HPV31, VEs were 51.6% (32.7-65.2%) and 58.1% (24.6-76.7%) for 3- and 2-doses, respectively. For HPV45, VEs were 76.1% (54.6-87.4%) and 77.7% (20.2-93.8%). Both schedules showed high VE against persistent HPV16, 18, and 31 infections. Indirect effects among unvaccinated women were 70.1% (49.8-82.2%) for HPV16 and 47.9% (5.0-71.4%) for HPV18. We demonstrated high VE against incident and persistent HPV16 and HPV18 infections up to 14 years after a 3-dose schedule, with no signs of waning and significant indirect effects. Comparable high VEs were found for the 2-dose schedule up to 9 years. Both schedules showed cross-protective effects against persistent HPV31 and HPV45 during prolonged follow-up.