Immune Responses After 2 Versus 3 Doses of HPV Vaccination up to 4½ Years After Vaccination: An Observational Study Among Dutch Routinely Vaccinated Girls

Abstract

Background: In 2014 the Netherlands switched from 3 to 2 doses for routine vaccination with the prophylactic bivalent human papillomavirus (HPV) vaccine. The current study explored whether antibody responses are noninferior after 2 versus 3 doses in girls.

Methods: Girls vaccinated at 12 years of age with 2 (at 0 and 6 months) or 3 doses (at 0, 1, and 6 months) of the bivalent HPV vaccine were identified in the vaccination registration system. Type-specific antibody concentrations and avidity against HPV-16/18/31/33/45/52/58 were assessed. Analyses were stratified for time since the first dose (0-2, 2-3, 3-4, or 4-4½ years). Noninferiority (margin, 0.5) of the 2- versus the 3-dose schedule in girls was examined.

Results: Geometric mean concentrations (GMCs) for vaccine types were only noninferior for 2 versus 3 doses for HPV-18 (at 2-3 years after the first dose; GMC ratio, 0.89; 95% confidence interval, .57-1.38) For vaccine types and cross-protective types (HPV-16/18/31/33/45), the avidity index was noninferior for the 2-dose compared with the 3-dose schedule, except for HPV-31 at 4-4½ years after the first dose and HPV-33 at 3-4 and 4-4½ years.

Conclusions: GMCs for HPV-16/18 were not noninferior for 2 versus 3 doses, except for HPV-18 (at 2-3 years after first dose). However, antibody avidity for these types showed noninferiority, independent of concentrations.

Keywords: GMC; HPV; antibody concentration; avidity; three-dose schedule.; two-dose schedule; vaccine.