• Robine Donken, Mirjam J Knol, Johannes A Bogaards, van der Klis Fiona R M FR Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), P.O Box 1, 3720 BA, Bilthoven, The Nethe, Chris J L M Meijer, and Hester E de Melker.
• Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), P.O Box 1, 3720 BA, Bilthoven, The Netherlands; Department of Pathology, VU University Medical Centre (VUmc), P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands. Electronic address: robine.donken@rivm.nl.
• J. Infect. 2015 Jul 1; 71 (1): 61-73.

BackgroundThe European Medicines Agency (EMA) recently approved two-dose immunization schedules for bivalent (HPV 16/18) and quadrivalent (HPV 6/11/16/18) human papillomavirus (HPV) vaccines in nine to fourteen and thirteen year-old-girls, respectively. Registration was based on trials comparing immunogenicity of two-dose schedules in girls 9-14 years to three-dose schedules in young women 15-26 years. We evaluate comparability of antibody levels between and within age groups and discuss potential implications for monitoring the effectiveness of HPV vaccination.MethodsA systematic literature search was performed for studies comparing immunogenicity of two- to three-dose schedules of HPV vaccination. We compared geometric mean concentrations (GMCs) of vaccine-type antibodies between different dosing schedules across different age groups. Meta-analysis was used to estimate pooled GMC ratios (bivalent vaccine) of two- compared with three-dose schedules within girls.FindingsFor both vaccines, two-dose immunization of girls yielded non-inferior GMCs relative to a three-dose schedule in young women up to respectively 36 and 48 months follow-up. Pooled GMC ratios for the bivalent vaccine within girls showed the two-dose schedule becoming inferior to the three-dose schedule in girls for HPV 16 at approximately two years after the first dose. For the quadrivalent vaccine, antibody responses for HPV-18 became inferior from 18 months follow-up onwards when comparing the two-dose schedule with the three-dose schedule within girls.ImplicationsTwo-dose immunization of girls has non-inferior immunogenicity compared to a three-dose schedule among young women. However, non-inferior immunogenicity of two- compared with three-dose schedules within girls has not been shown at all time points. Due to this inconclusive evidence, implementation of two-dose HPV vaccination needs to be monitored closely.Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

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