Optimal timing of HPV vaccination reduces high grade cytology at first cervical screening test

Background

HPV vaccination began in Ireland in 2010, offering Gardasil-4 to girls in first year senior school (age 11-14). At that time, girls up to 6th year in school (age 17-18) were offered vaccination. Gardasil-9 and gender-neutral vaccination were introduced in 2019 (age 11-14) with “catch-up” vaccination offered to girls up to 26 years.

Methods

HPV vaccination data was matched by individual identifiers with cervical screening data on women screened for the first time at age ≥25 during 2020-2024 (n = 74,847). HPV positivity and high-grade cytology rates were compared in participants who received the quadrivalent (Gardasil-4 2010-2019) vs nonavalent vaccines (Gardasil-9 2020-2023) and those aged 11- 14 years vs ≥ 15 years at vaccination.

Results

99.7% received Gardasil-4 with 43,256/74,847 (57.9%) aged 11-14 at vaccination; remainder aged ≥15. The mean age at first screening was 25.85 years (range 25-35; 95% were 25-29). 17,902/74,847 (23.9%) were HPV positive and had reflex cytology performed. The prevalence of high-grade cytology in the screened population was 776/74,847 (1.04%). Cohorts vaccinated ≥15 years had higher rates of high-grade cytology than those vaccinated prior to age 15 (1.20% vs 0.92%; p < 0.001). Association between older age at vaccination and higher rates of high-grade cytology persisted after adjustment for vaccine type (p<.001). On univariate analysis, cohorts vaccinated at the younger age had higher HPV positive rates (24.2% vs 23.5%; p = 0.039) but this did not persist after vaccine type adjustment. Odds of high-grade were 25% lower in younger girls.

Conclusions

This is the first direct evidence of the benefit of HPV vaccination at the optimum age in Ireland; optimal age at vaccination was associated with lower rates of high-grade cytology at first screening. Small numbers received Gardasil-9; while girls vaccinated at a younger age had higher HPV positivity rates, a reduction is anticipated once Gardasil-9 vaccinated cohorts are screened.

Key messages

• This is the first direct evidence of the benefit of HPV vaccination at the optimum age in Ireland.

• Odds of high-grade cytology at first screening were reduced by 25% in those vaccinated at the optimal age (11-14 years).