Impact of a population-based HPV vaccination program on cervical abnormalities: a data linkage study

Abstract

Background: Australia was one of the first countries to introduce a publicly funded national human papillomavirus (HPV) vaccination program that commenced in April 2007, using the quadrivalent HPV vaccine targeting 12- to 13-year-old girls on an ongoing basis. Two-year catch-up programs were offered to 14- to 17- year-old girls in schools and 18- to 26-year-old women in community-based settings. We present data from the school-based program on population-level vaccine effectiveness against cervical abnormalities in Victoria, Australia.

Methods: Data for women age-eligible for the HPV vaccination program were linked between the Victorian Cervical Cytology Registry and the National HPV Vaccination Program Register to create a cohort of screening women who were either vaccinated or unvaccinated. Entry into the cohort was 1 April 2007 or at first Pap test for women not already screening. Vaccine effectiveness (VE) and hazard ratios (HR) for cervical abnormalities by vaccination status between 1 April 2007 and 31 December 2011 were calculated using proportional hazards regression.

Results: The study included 14,085 unvaccinated and 24,871 vaccinated women attending screening who were eligible for vaccination at school, 85.0% of whom had received three doses. Detection rates of histologically confirmed high-grade (HG) cervical abnormalities and high-grade cytology (HGC) were significantly lower for vaccinated women (any dose) (HG 4.8 per 1,000 person-years, HGC 11.9 per 1,000 person-years) compared with unvaccinated women (HG 6.4 per 1,000 person-years, HGC 15.3 per 1,000 person-years) HR 0.72 (95% CI 0.58 to 0.91) and HR 0.75 (95% CI 0.65 to 0.87), respectively. The HR for low-grade (LG) cytological abnormalities was 0.76 (95% CI 0.72 to 0.80). VE adjusted a priori for age at first screening, socioeconomic status and remoteness index, for women who were completely vaccinated, was greatest for CIN3+/AIS at 47.5% (95% CI 22.7 to 64.4) and 36.4% (95% CI 9.8 to 55.1) for women who received any dose of vaccine, and was negatively associated with age. For women who received only one or two doses of vaccine, HRs for HG histology were not significantly different from 1.0, although the number of outcomes was small.

Conclusion: A population-based HPV vaccination program in schools significantly reduced cervical abnormalities for vaccinated women within five years of implementation, with the greatest vaccine effectiveness observed for the youngest women.

Figure 1

Data linkage process and exclusions for analysis.

Figure 2

Cervical abnormalities rates for vaccinated and unvaccinated women, by age in 2007. High-grade histology per 1,000 women years, by age in 2007. (a) (b) CIN 3/AIS histology per 1,000 women years, by age in 2007. (c) CIN 2 histology per 1,000 women years, by age in 2007. (d) CIN I histology per 1,000 women years, by age in 2007. (e) Low-grade cytology per 1,000 women years, by age in 2007. (f) High grade cytology per 1,000 women years, by age in 2007. All high grade histology is defined as CIN2, CIN3, AIS and mixed CIN3/AIS. Age is presented in years.

Figure 3

HPV vaccine effectiveness for cervical histological outcome, by age in 2007, for (a) completed vaccine course, for (b) any vaccine dose. All high-grade histology is defined as CIN2, CIN3, AIS and mixed CIN3/AIS. Vaccine effectiveness is defined as (1-adjusted hazard rate) x 100. Age in years, as of 2007.