RT Journal Article SR Electronic T1 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 JF BMJ Open JO BMJ Open FD British Medical Journal Publishing Group SP e015867 DO 10.1136/bmjopen-2017-015867 VO 7 IS 8 A1 Matti Lehtinen A1 Camilla Lagheden A1 Tapio Luostarinen A1 Tiina Eriksson A1 Dan Apter A1 Katja Harjula A1 Marjo Kuortti A1 Kari Natunen A1 Johanna Palmroth A1 Tiina Petäjä A1 Eero Pukkala A1 Mari Siitari-Mattila A1 Frank Struyf A1 Pekka Nieminen A1 Jorma Paavonen A1 Gary Dubin A1 Joakim Dillner YR 2017 UL http://bmjopen.bmj.com/content/7/8/e015867.abstract AB 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.