Ten-year follow-up of human papillomavirus vaccine efficacy against the most stringent cervical neoplasia end-point-registry-based follow-up of three cohorts from randomized trials

BMJ Open. 2017 Aug 18;7(8):e015867. doi: 10.1136/bmjopen-2017-015867.


Objective: Due to long lag time between infection/cancer diagnoses human papillomavirus (HPV) vaccination programs will deliver vaccine efficacy (VE) estimates against cancer end-points late. Cancer registry follow-up of population-based, randomised trial cohorts of vaccinated and unvaccinated women was undertaken for the estimation of VE against cervical intraepithelial neoplasia grade three and invasive cancer (CIN3+).

Methods: We report interim results with 98 561 person years of Finnish Cancer Registry -based follow-up of individually and/or cluster randomised cohorts of HPV-16/18 vaccinated and unvaccinated adolescent women enrolled in June 2003/2005, and between May 2004 and April 2005, respectively. The cohorts comprised 15 627 18- to 19-year-old unvaccinated women (NCT01393470), and 2 401 and 64 16- to 17-year-old HPV-16/18 vaccinated women participating the PATRICIA (NCT00122681) and HPV-012 (NCT00169494) trials, respectively. The age-aligned passive follow-up started 6 months after the clinical trials' end.

Results: During the follow-up of 4.5 to 10 years post enrolment we identified 75 cases of cervical intraepithelial neoplasia grade 3 (CIN3) and 4 cases of invasive cervical cancer (ICC) in the unvaccinated cohort, and 4 CIN3 cases in the HPV-16/18 vaccinated women. Diagnostic blocks were available for HPV typing from 87% of the cases. CIN3+ lesions were detectable in 54 cases. HPV16 was found in 26 of 50 unvaccinated CIN3+ cases, and in 3 CIN3+ cases in the HPV-16/18 vaccinated women. The latter were all baseline positive for cervical HPV16 DNA. Baseline data was not available for the unvaccinated women. Intention-to-treat VE against any CIN3+ was 66% (95% CI 8, 88).

Conclusions: Ten years post vaccination the AS04-adjuvanted HPV-16/18 vaccine shows continued efficacy against CIN3+ irrespectively of HPV type. Vaccine efficacy was not observed in baseline HPV16 DNA positive subjects.

Trial registration number: NCT01393470.

Keywords: HPV vaccines; cervical cancer; cin3+; long-term follow-up; randomized controlled trial; vaccine efficacy.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adjuvants, Immunologic
  • Adolescent
  • Adult
  • DNA, Viral
  • Double-Blind Method
  • Female
  • Finland / epidemiology
  • Follow-Up Studies
  • Human papillomavirus 16 / growth & development
  • Human papillomavirus 16 / immunology*
  • Human papillomavirus 18 / growth & development
  • Human papillomavirus 18 / immunology*
  • Humans
  • Incidence
  • Intention to Treat Analysis
  • Neoplasm Grading
  • Papillomaviridae / classification
  • Papillomaviridae / growth & development
  • Papillomaviridae / immunology
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines*
  • Registries
  • Treatment Outcome
  • Uterine Cervical Dysplasia / epidemiology
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / prevention & control*
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / prevention & control*
  • Uterine Cervical Neoplasms / virology
  • Vaccination*
  • Young Adult


  • Adjuvants, Immunologic
  • DNA, Viral
  • Papillomavirus Vaccines