The Long-Term Effect of 2 and 3 Doses of Bivalent HPV Vaccination Against HPV Infections: A Comparison Between 2...

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 1665 HAVANA women and 2441 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, HPV18, and HPV31 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.