Long-term Antibody Response to Human Papillomavirus Vaccines: Up to 12 Years of Follow-up in the Finnish Maternity Cohort

J Infect Dis. 2019 Jan 29;219(4):582-589. doi: 10.1093/infdis/jiy545.


Background: Most cervical cancers are caused by vaccine-preventable infections with human papillomaviruses (HPV). The HPV prophylactic vaccines Gardasil and Cervarix have been widely used for >10 years and are reported to induce high antibody levels. A head-to-head comparison of the antibody responses induced by the 2 vaccines has been performed only up to 5 years.

Methods: Among 3300 Finnish females aged 16-17 years who got 1 of the 2 HPV vaccines in phase 3 licensure trials, virtually all consented to registry-based long-term follow-up. Linkage with the Finnish Maternity Cohort found that they donated >2500 serum samples up to 12 years later. Sera of 337 (38.6%) Gardasil and 730 (30.3%) Cervarix vaccine recipients were retrieved from the Finnish Maternity Cohort biobank and type-specific anti-HPV antibody levels were determined using in-house multiplexed heparin-HPV pseudovirion Luminex assay.

Results: Anti-HPV-16 and anti-HPV-18 antibody levels remained stable and above natural infection-related antibody levels for up to 12 years for most vaccine recipients. The median antibody levels were higher among Cervarix recipients 7-12 years post vaccination (P < .0001).

Conclusions: The stability of vaccine-induced antibody levels is in accordance with the high long-term protection reported previously. The differences in antibody levels induced by the 2 vaccines imply that continued follow-up to identify possible breakthrough cases and estimation of the minimal protective levels of serum antibodies is a research priority.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Viral / blood
  • Antibody Formation*
  • Female
  • Finland
  • Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 / administration & dosage
  • Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 / immunology*
  • Humans
  • Immunoassay
  • Longitudinal Studies
  • Papillomaviridae / immunology*
  • Papillomavirus Vaccines / administration & dosage
  • Papillomavirus Vaccines / immunology*


  • Antibodies, Viral
  • Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18
  • Papillomavirus Vaccines
  • human papillomavirus vaccine, L1 type 16, 18