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


RESULTS
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.


CONCLUSIONS
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.


BACKGROUND
The Canadian Institutes of Health Research.
Centre de Recherche du CHU de Québec, Québec, QC, Canada; Département de Médecine Sociale et Préventive, Université Laval, Québec, QC, Canada.
Mélanie
M
Drolet
Centre de Recherche du CHU de Québec, Québec, QC, Canada; Département de Médecine Sociale et Préventive, Université Laval, Québec, QC, Canada.
Élodie
É
Bénard
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.
Marie-Claude
MC
Boily
The Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
Hammad
H
Ali
Unit of Virus, Lifestyle and Genes, The Danish Cancer Society Research Centre, Copenhagen, Denmark.
Louise
L
Baandrup
STD Control Branch of the California Department of Public Health, Richmond, CA, USA.
Heidi
H
Bauer
Virus Reference Department, Public Health England, London, UK.
Simon
S
Beddows
Centre de Recherche du CHU de Québec, Québec, QC, Canada; Département de Médecine Sociale et Préventive, Université Laval, Québec, QC, Canada.
Jacques
J
Brisson
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.
Julia M L
JM
Brotherton
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
Teresa
T
Cummings
The Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
Basil
B
Donovan
Melbourne Sexual Health Centre, Melbourne, VIC, Australia; Central Clinical School, Monash University, Alfred Hospital, Melbourne, VIC, Australia.
Christopher K
CK
Fairley
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), Centers for Disease Control and Prevention, Atlanta, GA, USA.
Elaine W
EW
Flagg
Research Department of Infection and Population Health, University College London, London, UK.
Anne M
AM
Johnson
Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Jessica A
JA
Kahn
Department of Mathematics and Statistics, University of Strathclyde, Glasgow, UK.
Kimberley
K
Kavanagh
Unit of Virus, Lifestyle and Genes, The Danish Cancer Society Research Centre, Copenhagen, Denmark; Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Susanne K
SK
Kjaer
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.
Erich V
EV
Kliewer
Centre de Recherche du CHU de Québec, Québec, QC, Canada; Département de Médecine Sociale et Préventive, Université Laval, Québec, QC, Canada.
Philippe
P
Lemieux-Mellouki
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), Centers for Disease Control and Prevention, Atlanta, GA, USA.
Lauri
L
Markowitz
Centre de Recherche du CHU de Québec, Québec, QC, Canada.
Aminata
A
Mboup
HIV and STI Department, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK.
David
D
Mesher
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, CT, USA.
Linda
L
Niccolai
Auckland Sexual Health Service, Auckland, New Zealand.
Jeannie
J
Oliphant
Health Protection Scotland, Glasgow, UK.
Kevin G
KG
Pollock
HIV and STI Department, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK.
Kate
K
Soldan
Research Department of Infection and Population Health, University College London, London, UK.
Pam
P
Sonnenberg
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.
Sepehr N
SN
Tabrizi
Research Department of Infection and Population Health, University College London, London, UK.
Clare
C
Tanton
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.
Marc
M
Brisson
D000293:Adolescent; D000328:Adult; D003218:Condylomata Acuminata / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D003362:Cost-Benefit Analysis; D056738:Cross Protection; D019049:Developed Countries; D005260:Female; D006801:Humans; D017589:Immunization Programs / Q000191:economics; D008297:Male; D027383:Papillomaviridae / Q000276:immunology* / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination
D053918:Papillomavirus Vaccines