title: Characteristics of a cluster-randomized phase IV human papillomavirus vaccination effectiveness trial.
abstract: High-risk human papillomaviruses (hrHPV) cause anogenital and oropharyngeal cancers. HPV-16/18 virus-like particle vaccine formulated with an AS04 adjuvant is very efficacious against hrHPV associated precancers but the herd effects of different vaccination scenarios are not known. Our cluster randomized trial (NCT00534638) assesses the overall and herd effects of vaccinating girls vs. girls and boys. In two school-years (2007-2008 and 2008-2009) we invited 80,272 1992-1995 born early adolescents to a CRT in 33 communities a priori stratified by low, intermediate and high HPV-16/18 seroprevalence. In 11 Arm A communities 90% of participating girls and boys were assigned to receive HPV-16/18 vaccine, in 11 Arm B communities 90% of girls were assigned to receive HPV-16/18 vaccine - boys were assigned to receive hepatitis B-virus (HBV) vaccine, and in 11 Arm C communities all were assigned to receive HBV-vaccine. Prevalence of HPV in vaccinated and unvaccinated girls is studied at age 18.5 years. Recruitment resulted in equal enrolment of four birth cohorts (born 1992-1995) comprising altogether 32,175 (40% response) early adolescents: 20,514 girls (50.5-53.0% response by arm) and 11,661 boys (21.9-31.6%% response by arm). At the age of 15 years, 79.3% of the vaccinees completed a questionnaire. Among them >98% were living at, and during the week-ends 1.3-1.6% stayed outside, the study site communities. Smoking habit and alcohol consumption were similar in the different trial arms, also mean-age of menarche (12.4 years) and 1st ejaculation (12.6 years), and sexual behaviour (among those <25%, who had had sexual debut) did not differ by arm: mean-age at the sexual debut 14.3 and 14.4 in girls and boys, and proportions of those with multiple (≥5) life-time sexual partners (6.5-7.5%) at the age of 15 years. Uniform residential, life-style and sexual behaviour characteristics indicate successful randomization/enrolment of the CRT. Our CRT will verify modelled predictions on up to 31% herd effect of vaccinating both girls and boys with moderate vaccine coverage - quantifying overall effectiveness of different strategies which will soon guide how to implement HPV vaccination.
authors.affiliation: University of Tampere, Tampere, Finland. Electronic address: llmale@uta.fi.
authors.forename: Matti
authors.initials: M
authors.lastname: Lehtinen
authors.affiliation: Family Federation of Finland, Helsinki and Oulu, Finland.
authors.forename: Dan
authors.initials: D
authors.lastname: Apter
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Iacopo
authors.initials: I
authors.lastname: Baussano
authors.affiliation: University of Tampere, Tampere, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Eriksson
authors.affiliation: University of Tampere, Tampere, Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Natunen
authors.affiliation: University of Helsinki, Helsinki, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Paavonen
authors.affiliation: National Institute for Health & Welfare, Finland.
authors.forename: Simopekka
authors.initials: S
authors.lastname: Vänskä
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Dan
authors.initials: D
authors.lastname: Bi
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: David
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Sanjoy
authors.initials: S
authors.lastname: Datta
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Struyf
authors.affiliation: DDL Diagnostic Laboratory, Rijswijk, The Netherlands.
authors.forename: David
authors.initials: D
authors.lastname: Jenkins
authors.affiliation: University of Tampere, Tampere, Finland.
authors.forename: Eero
authors.initials: E
authors.lastname: Pukkala
authors.affiliation: Bill and Melinda Gates Foundation, Seattle, WA, USA.
authors.forename: Geoff
authors.initials: G
authors.lastname: Garnett
authors.affiliation: GSK Vaccines, King of Prussia, PA, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Dubin
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000293:Adolescent; D002648:Child; D005260:Female; D017325:Hepatitis B Vaccines / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D052162:Human papillomavirus 16 / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000276:immunology*; D006801:Humans; D032521:Immunity, Herd / Q000276:immunology*; D008297:Male; D032541:Mass Vaccination; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000276:immunology; D053918:Papillomavirus Vaccines / Q000276:immunology*; D016036:Seroepidemiologic Studies; D012725:Sexual Behavior / Q000706:statistics & numerical data; D011795:Surveys and Questionnaires; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control; D058425:Vaccines, Virus-Like Particle / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D017325:Hepatitis B Vaccines; D053918:Papillomavirus Vaccines; D058425:Vaccines, Virus-Like Particle
keywords: HPV-vaccines; Herd effect; Human papillomavirus