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Lancet Infect Dis. 2015 May;15(5):565-80. doi: 10.1016/S1473-3099(14)71073-4. Epub 2015 Mar 3.

Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis.

Author information

1
Centre de Recherche du CHU de Québec, Québec, QC, Canada; Département de Médecine Sociale et Préventive, Université Laval, Québec, QC, Canada.
2
Centre de Recherche du CHU de Québec, Québec, QC, Canada; Département de Médecine Sociale et Préventive, Université Laval, Québec, QC, Canada; Department of Infectious Disease Epidemiology, Imperial College London, London, UK.
3
The Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
4
Unit of Virus, Lifestyle and Genes, The Danish Cancer Society Research Centre, Copenhagen, Denmark.
5
STD Control Branch of the California Department of Public Health, Richmond, CA, USA.
6
Virus Reference Department, Public Health England, London, UK.
7
National HPV Vaccination Program Register, Victorian Cytology Service, East Melbourne, Melbourne, VIC, Australia; Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
8
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
9
Melbourne Sexual Health Centre, Melbourne, VIC, Australia; Central Clinical School, Monash University, Alfred Hospital, Melbourne, VIC, Australia.
10
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), Centers for Disease Control and Prevention, Atlanta, GA, USA.
11
Research Department of Infection and Population Health, University College London, London, UK.
12
Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA.
13
Department of Mathematics and Statistics, University of Strathclyde, Glasgow, UK.
14
Unit of Virus, Lifestyle and Genes, The Danish Cancer Society Research Centre, Copenhagen, Denmark; Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
15
Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Cancer Control Research, British Columbia Cancer Agency, Vancouver, BC, Canada; Epidemiology and Cancer Registry, CancerCare Manitoba, Winnipeg, MB, Canada.
16
Centre de Recherche du CHU de Québec, Québec, QC, Canada.
17
HIV and STI Department, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK.
18
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, CT, USA.
19
Auckland Sexual Health Service, Auckland, New Zealand.
20
Health Protection Scotland, Glasgow, UK.
21
Department of Obstetrics and Gynaecology, The University of Melbourne, Melbourne, VIC, Australia; Regional WHO HPV Reference Laboratory, Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville, VIC, Australia; Murdoch Childrens Research Institute, Parkville, VIC, Australia.
22
Centre de Recherche du CHU de Québec, Québec, QC, Canada; Département de Médecine Sociale et Préventive, Université Laval, Québec, QC, Canada; Department of Infectious Disease Epidemiology, Imperial College London, London, UK. Electronic address: mbrisson@uresp.ulaval.ca.

Abstract

BACKGROUND:

Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations.

METHODS:

We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I(2) and χ(2) statistics and we did trends analysis to examine the dose-response association between HPV vaccination coverage and each study effect measure.

FINDINGS:

We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19-0·52) and anogenital warts decreased significantly by 61% (0·39, 0·22-0·71) in girls 13-19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0·72, 95% CI 0·54-0·96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0·66 [95% CI 0·47-0·91]) and in women 20-39 years of age (0·68 [95% CI 0·51-0·89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0·50, 95% CI 0·34-0·74]) and in anogenital warts (0·86 [95% CI 0·79-0·94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects.

INTERPRETATION:

Our results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement.

FUNDING:

The Canadian Institutes of Health Research.

PMID:
25744474
PMCID:
PMC5144106
DOI:
10.1016/S1473-3099(14)71073-4
[Indexed for MEDLINE]
Free PMC Article

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