title: Assessment of herd immunity and cross-protection after a human papillomavirus vaccination programme in Australia: a repeat cross-sectional study.
abstract: 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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Australian National Health and Medical Research Council and Cancer Council Victoria.
authors.affiliation: Regional World Health Organization Human Papillomavirus Laboratory Network, Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville, VIC, Australia; Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, VIC, Australia; Department of Microbiology, Royal Children's Hospital, Parkville, VIC, Australia; Murdoch Childrens Research Institute, Parkville, VIC, Australia. Electronic address: sepehr.tabrizi@thewomens.org.au.
authors.forename: Sepehr N
authors.initials: SN
authors.lastname: Tabrizi
authors.affiliation: National HPV Vaccination Program Register, Victorian Cytology Service, East Melbourne, VIC, Australia; Sydney University Discipline of Paediatrics and Child Health, Children's Hospital Westmead, Sydney, NSW, Australia.
authors.forename: Julia M L
authors.initials: JM
authors.lastname: Brotherton
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
authors.forename: John M
authors.initials: JM
authors.lastname: Kaldor
authors.affiliation: Sydney University Discipline of Paediatrics and Child Health, Children's Hospital Westmead, Sydney, NSW, Australia.
authors.forename: S Rachel
authors.initials: SR
authors.lastname: Skinner
authors.affiliation: School of Public Health and Community Medicine, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Bette
authors.initials: B
authors.lastname: Liu
authors.affiliation: Family Planning New South Wales, Ashfield, NSW, Australia.
authors.forename: Deborah
authors.initials: D
authors.lastname: Bateson
authors.affiliation: Family Planning Victoria, Box Hill, VIC, Australia; Department of Obstetrics and Gynecology, Monash University, Clayton, VIC, Australia.
authors.forename: Kathleen
authors.initials: K
authors.lastname: McNamee
authors.affiliation: Family Planning Western Australia, Northbridge, WA, Australia.
authors.forename: Maria
authors.initials: M
authors.lastname: Garefalakis
authors.affiliation: Regional World Health Organization Human Papillomavirus Laboratory Network, Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville, VIC, Australia; Murdoch Childrens Research Institute, Parkville, VIC, Australia.
authors.forename: Samuel
authors.initials: S
authors.lastname: Phillips
authors.affiliation: Regional World Health Organization Human Papillomavirus Laboratory Network, Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville, VIC, Australia; Murdoch Childrens Research Institute, Parkville, VIC, Australia.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Cummins
authors.affiliation: National HPV Vaccination Program Register, Victorian Cytology Service, East Melbourne, VIC, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Malloy
authors.affiliation: Regional World Health Organization Human Papillomavirus Laboratory Network, Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville, VIC, Australia; Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, VIC, Australia; Department of Microbiology, Royal Children's Hospital, Parkville, VIC, Australia; Murdoch Childrens Research Institute, Parkville, VIC, Australia.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Garland
mesh_terms: D000293:Adolescent; D052685:Alphapapillomavirus / Q000276:immunology*; D001315:Australia / Q000453:epidemiology; D056738:Cross Protection; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006284:Health Plan Implementation; D006801:Humans; D032521:Immunity, Herd / Q000276:immunology*; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000276:immunology*; D015995:Prevalence; D014611:Vaccination; D055815:Young Adult
chemical_list: D053918:Papillomavirus Vaccines