Monitoring of the quadrivalent HPV vaccine (Gardasil) is conducted in the Nordic long-term follow-up (LTFU) study, which is an ongoing extension of the randomized, placebo-controlled, double-blind phase 3 trial (FUTURE 2). The aim was to investigate the effectiveness of the 4-valent HPV vaccine on the incidence of HPV 16/18-related cervical intraepithelial neoplasia (CIN) 2 or worse in 16-to 23-year old women.
Even though the quadrivalent HPV vaccine has shown excellent efficacy in randomized clinical studies, data on real world effectiveness are important. The study aim was to use individual information on HPV vaccination status to assess subsequent risk of cervical lesions among women from the general population in Denmark.
In a Danish nationwide study of real world effectivenes of Gardasil, we identified all girls and women born in Denmark in 1989–1999 and obtained information on individual HPV vaccination status in 2006–2012 from nationwide registries. Incident cases of cervical lesions were identified by linkage to the nationwide Pathology Data Bank. Incident cases of cervical lesions were identified by linkage to the nationwide Pathology DataBank. We compared vaccinated and unvaccinated girls and women stratified by birth cohort
In the LFTU study, all women in the Nordic part of the FUTURE 2 trial were followed through different national registries (Denmark, Iceland, Norway and Sweden) for effectiveness data. Effectiveness analyses started approximately 2 years following completion of Protocol 015 and has been occuring approximately every 2 years thereafter. The cohort included a total of approximately 2,700 subjects who received qHPV vaccine at the start of Protocol 015.
Risk of CIN2/3 was statistically significantly reduced among Danish vaccinated women in birth cohorts 1991 to 1994 ( HR=0.56, (95% CI=0.37-0.84) in the 1991-1992 cohort). The risk of CIN3 was significantly reduced among vaccinated women in birth cohorts 1993-1994 (HR=0.20, (95% CI-0.06-0.71)).
In the analysis of the long-term effectiveness including a follow-up period up to 10 years, there were 1,281 subjects that contributed to the follow-up period out of a total of 1,984 eligible subjects in the per-protocol population. No new cases of HPV 16/18-related CIN 2 or worse were observed.
Already after a limited number of years (~ 6 years) following licensure of the quadrivalent HPV vaccine in Denmark, a reduced risk of cervical lesions is observed at population level.
The quadrivalent HPV vaccine shows continued protection in women through 8 years, with a trend towards 10 years.