Seizing the day is pivotal in vaccination licensure studies, especially when
the new vaccine is supposed to protect against a chronic infection with long lead time
between the preventable infection and diagnosis of the to-be prevented chronic disease.
With appropriate population-based design, that relied on the unique Finnish personal
identification number comprehensive health register follow-up was feasible for the
definition of safety, immunogenicity and efficacy of both the bivalent and quadrivalent
human papillomavirus (HPV) vaccines soon after their licensure. In essentially HPV
vaccination naïve population head-to-head comparison of the two vaccines was also
feasible. Respectively, in 2002 and 2004 enrolled 1,749 and 4,809 adolescent girls
around the ages of 16-17 years were respectively participated in two phase III licensure
trials (FUTURE II and PATRICIA) of the quadrivalent and bivalent HPV vaccines. At
the same time in 2003 and 2005, 15,615 adolescent, 18-19 year old girls from adjacent
birth cohorts were enrolled into a concomitant control cohort. Linkage of the HPV
vaccinees cohort with the population-based Finnish Maternity Cohort Serum Bank
enabled comparative head-to-head studies on the quadrivalent and bivalent vaccineinduced total and neutralizing antibody responses, which were proven to be equally
sustainable up to 12 years post-vaccination, however, with a logarithmic difference in
the antibody levels. Linkage of the HPV vaccinees cohort and the concomitant control
cohorts with the country-wide Finnish Cancer Registry has enabled the definition of
vaccine efficacy (VE) against invasive cervical cancer and cervical intraepithelial
neoplasia grade 3 (CIN3+) during 18 years of follow-up with comparable intention-totreat VEs of 68.4% and 64.5%. Linkage with the Hostital Discharge Registry has
provided a sentinel, most notably for new onset autoimmune diseases (NOADs) that
proved to be more than twice as sensitive as reporting of serious adverse effects but as
such did not identify any NOAD-incidence differences between the HPV and control
vaccines or unvaccinated population.
Keywords: Efficacy, End-point, Enrolment, Follow-up, Health registry, Immunogenicity, Population-based study, Randomization, Safety, Vaccine efficacy.