Ten-year immune persistence and safety of the HPV-16/18 AS04-adjuvanted vaccine in females vaccinated at 15-55 years of age

Cancer Med. 2017 Nov;6(11):2723-2731. doi: 10.1002/cam4.1155. Epub 2017 Oct 5.


Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV-16/18 from prophylactic vaccination remains unknown. We investigated the 10-year immune response and long-term safety profile of the HPV-16/18 AS04-adjuvanted vaccine (AS04-HPV-16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04-HPV-16/18 vaccine in the primary phase-III study (NCT00196937) were invited to attend annual evaluations for long-term immunogenicity and safety. Anti-HPV-16/18 antibodies in serum and cervico-vaginal secretions (CVS) were measured using enzyme-linked immunosorbent assay (ELISA). Serious adverse events (SAEs) were recorded throughout the follow-up period. Seropositivity rates for anti-HPV-16 remained high (≥96.3%) in all age groups 10 years after first vaccination. It was found that 99.2% of 15-25-year olds remained seropositive for anti-HPV-18 compared to 93.7% and 83.8% of 26-45-year olds and 45-55-year olds, respectively. Geometric mean titers (GMT) remained above natural infection levels in all age groups. Anti-HPV-16 and anti-HPV-18 titers were at least 5.3-fold and 3.1-fold higher than titers observed after natural infection, respectively, and were predicted to persist above natural infection levels for ≥30 years in all age groups. At Year 10, anti-HPV-16/18 antibody titers in subjects aged 15-25 years remained above plateau levels observed in previous studies. Correlation coefficients for antibody titers in serum and CVS were 0.64 (anti-HPV-16) and 0.38 (anti-HPV-18). This study concluded that vaccinated females aged 15-55 years elicited sustained immunogenicity with an acceptable safety profile up to 10 years after primary vaccination, suggesting long-term protection against HPV.

Keywords: AS04-HPV-16/18 vaccine; older women; persistence; safety.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / analysis
  • Antibodies, Viral / blood*
  • Bodily Secretions / immunology
  • Cervix Uteri / immunology
  • Female
  • Follow-Up Studies
  • Human papillomavirus 16 / immunology*
  • Human papillomavirus 18 / immunology*
  • Humans
  • Middle Aged
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Vaccines / adverse effects
  • Papillomavirus Vaccines / immunology*
  • Uterine Cervical Neoplasms / prevention & control*
  • Vaccination* / adverse effects
  • Vagina / immunology
  • Young Adult


  • Antibodies, Viral
  • Papillomavirus Vaccines