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Assessment of herd immunity and cross-protection after a human papillomavirus vaccination programme in Australia: a repeat cross-sectional study

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Summary

Background

After the introduction of a quadrivalent human papillomavirus (HPV) vaccination programme in Australia in April, 2007, we measured the prevalence of vaccine-targeted and closely related HPV types with the aim of assessing direct protection, cross-protection, and herd immunity.

Methods

In this repeat cross-sectional study, we recruited women aged 18–24 years who attended Pap screening between October, 2005, and July, 2007, in three major metropolitan areas of Australia to form our prevaccine-implementation sample. For our postvaccine-implementation sample, we recruited women aged 18–24 years who attended Pap screening in the same three metropolitan areas from August, 2010, to November, 2012. We compared the crude prevalence of HPV genotypes in cervical specimens between the prevaccine and the postvaccine implementation groups, with vaccination status validated against the National HPV Vaccination Program Register. We estimated adjusted prevalence ratios using log linear regression. We estimated vaccine effectiveness both for vaccine-targeted HPV types (16, 18, 6, and 11) and non-vaccine but related HPV types (31, 33, and 45).

Findings

202 women were recruited into the prevaccine-implementation group, and 1058 were recruited into the postvaccine-implementation group. Crude prevalence of vaccine-targeted HPV genotypes was significantly lower in the postvaccine-implementation sample than in the prevaccine-implementation sample (58 [29%] of 202 vs 69 [7%] of 1058; p<0·0001). Compared with the prevaccine-implementation sample, adjusted prevalence ratios for vaccine-targeted HPV genotypes were 0·07 (95% CI 0·04–0·14; p<0·0001) in fully vaccinated women and 0·65 (0·43–0·96; p=0·03) in unvaccinated women, which suggests herd immunity. No significant declines were noted for non-vaccine-targeted HPV genotypes. However, within the postvaccine-implementation sample, adjusted vaccine effectiveness against vaccine-targeted HPV types for fully vaccinated women compared with unvaccinated women was 86% (95% CI 71–93), and was 58% (26–76) against non-vaccine-targeted but related genotypes (HPV 31, 33, and 45).

Interpretation

6 years after the initiation of the Australian HPV vaccination programme, we have detected a substantial fall in vaccine-targeted HPV genotypes in vaccinated women; a lower prevalence of vaccine-targeted types in unvaccinated women, suggesting herd immunity; and a possible indication of cross-protection against HPV types related to the vaccine-targeted types in vaccinated women.

Funding

Australian National Health and Medical Research Council and Cancer Council Victoria.

Introduction

In Australia, a fully government-funded human papillomavirus (HPV) vaccination programme started in April, 2007, using the quadrivalent vaccine, which protects against HPV types 6 and 11, the main causes of most genital warts,1 and types 16 and 18, the main causes of most HPV-associated anogenital neoplasia.2 Between April, 2007, and the end of December, 2009, the programme used a catch-up strategy for girls aged 12–17 years delivered through schools and for women aged up to 26 years through community providers. Since 2009, the continuing school programme routinely vaccinates girls in the first year of high school (aged 12–13 years), and boys of the same age were added in 2013.

HPV vaccinations given in schools are systematically reported to the National HPV Vaccination Program Register,3 and on a voluntary basis from community providers. On the basis of register data, the catch-up programme achieved high coverage, with at least one dose received by 83% of girls aged 12–17 years, and three doses received by 70% (fully vaccinated).4 Women aged 18–26 years had lower coverage than the younger age group (55% received one dose and 32% received three doses).5 Findings from separate population surveys6, 7 have suggested that register-based coverage estimates for the community programme underestimated coverage by 5–15%.

Australian researchers have already reported findings about several population-based indicators of vaccine programme effectiveness, including substantial reductions in cases of genital warts diagnosed at sexual health clinics8, 9 and rates of histologically confirmed high-grade cervical lesions10 in young women in vaccinated cohorts.11, 12, 13 These reductions in HPV-related diseases strongly suggest that the population prevalence of vaccine-targeted HPV types has declined since the vaccination programme began. We provided the world's first confirmation of this decline, when we reported the results of an interim analysis of the initial 404 women enrolled into a study of HPV prevalence in young women.14 We now report on the conclusion of this study, using vaccination status validated against the vaccination register, and with the goals of more accurately measuring the magnitude of the reduction in prevalence of targeted HPV types, investigating herd immunity against infection in unvaccinated women, and assessing evidence for cross-protection in vaccinated women against genetically related HPV types.

Section snippets

Participants

As described previously,14 this study was designed as a repeat cross-sectional study to compare HPV prevalence in two samples of women, recruited from family planning clinics in three major metropolitan areas of Australia (Sydney, Melbourne, and Perth). The prevaccine-implementation sample, which was a subset of the women that we assessed in the Women, Human papillomavirus prevalence, Indigenous, Non-indigenous, Urban, Rural Study (WHINURS),15 included women aged 18–24 years who attended family

Results

During the postvaccine-implementation phase, family planning clinics recruited 1058 age-eligible (18–24 years) women whose results were compared with 202 women in the same age group recruited in the prevaccine-implementation phase. Women in the postvaccine-implementation sample were more likely to be using hormonal contraception than were women in the prevaccine-implementation sample and were slightly younger, but were similar with respect to other characteristics (table 1).

The crude prevalence

Discussion

Using a repeat cross-sectional study design and recruiting participants from clinical sites with sentinel surveillance, we have confirmed our observation from an interim analysis that a substantial reduction in prevalence of vaccine-preventable HPV genotype infections has occurred after implementation of Australia's National HPV Vaccination Program. The size, timing, and specificity of this fall suggest that it is a true biological effect of vaccination and not due to changes in sexual

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