ArticlesPopulation-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis
Introduction
Since 2007, 52 out of 195 countries worldwide have implemented human papillomavirus (HPV) vaccination programmes, including 41% of high-income countries and 15% of low-income and middle-income countries.1, 2, 3, 4 The population-level effect of HPV vaccination programmes is expected to vary substantially between these countries, depending on the vaccine used, implementation strategies, and vaccination coverage achieved. Two HPV vaccines are currently available worldwide: the bivalent vaccine, which targets HPV types 16 and 18 (which are associated with 70–80% of cervical cancers globally5), and the quadrivalent vaccine, which also targets HPV types 6 and 11 (associated with 85–95% of cases of anogenital warts6). Most high-income countries are using the quadrivalent vaccine, whereas a mixed picture exists for low-income and middle-income countries.2, 7 Although all HPV vaccination programmes target pre-adolescent girls (and might also include catch-up programmes for older girls and women), a few countries, such as the USA and Australia, have recently begun to include boys.8, 9 Finally, in high-income countries, vaccination coverage in the younger cohorts of girls ranges from nearly 90% to less than 50%, mostly depending on whether the countries have school-based or non-school-based vaccination programmes.10
Large international randomised controlled clinical trials have shown both HPV vaccines to be safe and well tolerated, highly efficacious against vaccine-type persistent HPV infection and precancerous cervical lesions in women (vaccine efficacy 93–100%),11, 12 and to provide some degree of cross-protection against three non-vaccine types (HPV types 31, 33, and 45),12, 13, 14 which are associated with 10–15% of cervical cancers worldwide.15 Existing evidence from clinical trials also suggests that cross-protective vaccine efficacy estimates against infections and lesions associated with HPV types 31, 33, and 45 are higher for the bivalent vaccine than for the quadrivalent vaccine.16 Following clinical trials, mathematical models have been used to predict the long-term population-level effectiveness and cost-effectiveness of vaccination programmes delivered in different settings. Modelling studies have consistently predicted that the overall burden of HPV-related diseases in women will decrease substantially in the next few decades through vaccination, and that vaccination of girls against HPV is highly cost effective in most countries.17, 18, 19 Despite consistency in model predictions of the direct effects of HPV vaccination in vaccinated girls, uncertainty remains about the potential population-level effects of cross-protection and herd protection (eg, the indirect consequences of vaccinating girls on HPV in unvaccinated boys, men, and adult women), and the vaccination coverage necessary to achieve substantial herd effects.20, 21, 22, 23, 24 This information is crucial to help guide vaccine choices and inform decisions about vaccination of boys and men.
Now that more than 7 years have elapsed since the implementation of the first HPV vaccination programmes in 2007 (appendix pp 2–4), it is timely to verify whether or not the promising results from clinical trials and model projections are materialising at the population level. An increasing number of post-vaccination surveillance studies have recently been published using several intermediate endpoints (eg, HPV infection, anogenital warts, and precancerous cervical lesions). The aim of this systematic review and meta-analysis is to summarise existing evidence about the population-level effect of HPV vaccination, as measured in time-trend studies in girls and young women targeted for vaccination, and in boys, men, and older women. We focused on three HPV-related endpoints: HPV infection, anogenital warts, and high-grade cervical lesions.
Section snippets
Search strategy and selection criteria
We systematically reviewed the global literature and report it in accordance with the PRISMA guidelines.25 Studies were eligible for inclusion if they fulfilled the following criteria: they provided data about at least one endpoint of HPV infection, anogenital warts, histopathologically confirmed high-grade cervical lesions (cervical intraepithelial neoplasia [CIN] 2 or worse); if they assessed the population-level effect by comparing the frequency (prevalence or incidence) of the endpoint
Results
In our searches we identified 661 articles and 29 conference abstracts, of which 20 records met the inclusion criteria (seven on HPV infection,31, 32, 33, 34, 35, 36, 37 11 on anogenital warts,38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 and two on high-grade cervical lesions;49, 50 figure 1, table). The studies were done in nine high-income countries (the USA, Australia, England, Scotland, New Zealand, Sweden, Denmark, Canada, and Germany) and assessed the population-level consequences of
Discussion
This systematic review and meta-analysis, representing more than 140 million person-years of follow-up data from nine high-income countries, reports significant population-level decreases in HPV-related outcomes up to 4 years after the implementation of HPV vaccination programmes. In countries with high vaccination coverage, HPV16 and HPV18 infection, and anogenital warts decreased by more than 60% in girls younger than 20 years of age, starting after the first year of the vaccination
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Joint first authors