Effectiveness of bivalent HPV vaccination against genital HPV DNA-positivity of a catch-up campaign at age 13-16 years compared to routine vaccination at age 12 years: a biennial repeated cross-sectional study

Abstract

Background: The Netherlands is one of few countries worldwide which has used the bivalent HPV vaccine for girls-only for over a decade. This allows assessment of vaccine effectiveness (VE) against female genital HPV DNA-positivity of this vaccine in an observational post-licencing real-world setting. Additionally, it is unclear whether catch-up vaccination campaigns result in similar VE as routine vaccination. Therefore, type-specific and grouped VE were assessed and compared for women who had been eligible for catch-up vaccination at 13-16 years with those who had been eligible for routine vaccination at 12 years.

Methods: PASSYON is a Dutch biennial repeated cross-sectional (2011-2021) study among sexual health clinic clients aged 16-24 years old. Women provided self-collected vaginal samples, questionnaires on demographics and sexual behaviour were administered, and women self-reported HPV vaccination status. Samples were analysed using a PCR-based assay (SPF₁₀-LiPA₂₅). Type-specific and grouped VE estimates, adjusted with propensity score stratification, were assessed against genital positivity for 14 HPV types. VE for targeted and non-targeted genotypes were compared between women who had been eligible for the catch-up and those who had been eligible for routine vaccination.

Results: The study included 4488 female participants who had been eligible for HPV vaccination and provided genital swabs (1561 eligible for catch-up, 2927 for routine vaccination). Very high VE against genital HPV-16 and HPV-18 was observed (resp. 93.5% and 89.5%) and significant cross-protection against six other genotypes (HPV-31/33/35/45/52/58), varying from 18.0% (HPV-52) to 79.6% (HPV-45). VE estimates were comparable between women who had been eligible for the catch-up campaign and those eligible for routine vaccination: VE HPV-16/HPV-18: 92.2% (95%CI: 87.9-94.9) vs. 91.8% (95%CI: 86.0-95.2).

Conclusions: In real-world settings, the VE of bivalent vaccine is high against targeted genotypes, with cross-protection against 6 other genotypes. Catch-up campaigns up to age 16 years can be as effective as routine vaccination at age 12, although it is recommendable to provide HPV vaccination at an age at which most are likely not sexually active yet. This may inform countries considering catch-up campaigns when introducing or extending the use of HPV vaccination within their national immunisation programmes.

Keywords: Bivalent vaccine; Catch-up campaign; Human papillomavirus; Observational study; Propensity score; Prophylactic vaccination; Vaccine effectiveness.

Fig. 1

Type-specific and grouped prevalences and 95% confidence intervals of genital HPV DNA-positivity among female participants who had been eligible for HPV vaccination in the Netherlands from the PASSYON study (2011–2021), by vaccination status. 2vHPV is DNA-positive for at least one of HPV-16/HPV-18; crosstypes 1 is DNA-positive for at least one of HPV-31/HPV-33/HPV-45; crosstypes 2 is DNA-positive for at least one of HPV-31/HPV-33/HPV-35/HPV-45/HPV-52/HPV-58; 9vhrHPV is DNA positive for at least one of HPV-16/HPV-18/HPV-31/HPV-33/HPV-45/HPV-52/HPV-58; hrHPV is DNA-positive for at least one of 16/18/31/33/35/39/45/51/52/56/58/59. Abbreviations: 2vHPV, bivalent HPV; 9vhrHPV, nonavalent high-risk HPV; HPV, human papillomavirus; hrHPV, high-risk HPV

Fig. 2

Type-specific and grouped vaccine effectiveness of the bivalent HPV vaccine against genital HPV DNA-positivity for female participants who had been eligible for HPV vaccination included in the PASSYON study, the Netherlands, 2011–2021. 2vHPV is DNA-positive for at least one of HPV-16/HPV-18; crosstypes 1 is DNA-positive for at least one of HPV-31/HPV-33/HPV-45; crosstypes 2 is DNA-positive for at least one of HPV-31/HPV-33/HPV-35/HPV-45/HPV-52/HPV-58; 9vhrHPV is DNA positive for at least one of HPV-16/HPV-18/HPV-31/HPV-33/HPV-45/HPV-52/HPV-58; hrHPV is DNA-positive for at least one of 16/18/31/33/35/39/45/51/52/56/58/59. Abbreviations: 2vHPV, bivalent HPV; 9vhrHPV, nonavalent high-risk HPV; CI, confidence interval; HPV, human papillomavirus; hrHPV, high-risk HPV; VE, vaccine effectiveness

Fig. 3

Stratified analyses of type-specific and grouped vaccine effectiveness of the bivalent HPV vaccine against genital HPV DNA-positivity for female participants who had been eligible for HPV vaccination within the catch-up campaign and routine vaccination included in the PASSYON study, the Netherlands, 2011–2021. A presents stratified VE analyses by birth cohort, where birth cohort 1993–1996 had been eligible for the catch-up campaign and birth cohort ≥ 1997 for routine vaccination. B presents stratified analyses by having been sexually active before or at the same age as having been eligibility for HPV vaccination for women of the catch-up cohort. 2vHPV is DNA-positive for at least one of HPV-16/HPV-18; crosstypes 1 is DNA-positive for at least one of HPV-31/HPV-33/HPV-45; crosstypes 2 is DNA-positive for at least one of HPV-31/HPV-33/HPV-35/HPV-45/HPV-52/HPV-58; 9vhrHPV is DNA positive for at least one of HPV-16/HPV-18/HPV-31/HPV-33/HPV-45/HPV-52/HPV-58; hrHPV is DNA-positive for at least one of 16/18/31/33/35/39/45/51/52/56/58/59. Abbreviations: 2vHPV, bivalent HPV; 9vhrHPV, nonavalent high-risk HPV; HPV, human papillomavirus; hrHPV, high-risk HPV; VE, vaccine effectiveness