title: Enrolment of 22,000 adolescent women to cancer registry follow-up for long-term human papillomavirus vaccine efficacy: guarding against guessing.
abstract: Human papillomaviruses (HPVs, most notably types 16 and 18) cause cervical carcinoma, the second most common cancer among women. Vaccination of adolescents against HPV16/18 might prevent large proportion of cervical and other anogenital cancers. However, because of ethical reasons this cannot be proven by clinical studies. To determine the long-term vaccine efficacy (VE) of HPV16/18 virus-like-particle (VLP) vaccine against cervical carcinoma in situ (CIS+) and invasive cervical carcinoma, the following three population-based cohorts of adolescent women have been enrolled: (1) women vaccinated with the HPV vaccine; (2) women vaccinated with hepatitis A control vaccine; and (3) unvaccinated control women. These cohorts will be passively followed for cumulative incidence of CIS+ endpoints by population-based cancer registry. Overall 24,046 16- to 17-year-old adolescent women from 18 cities in Finland were invited between May 2004 and June 2005 to participate in a phase III trial with bivalent HPV16/18 VLP vaccine. A total of 58,996 18- to 19-year-old women were invited in May 2005 to participate as unvaccinated controls. Women who reported their willingness to participate in an HPV vaccination trial had they been 1-2 years younger were eligible. Cumulative incidence (CI) of CIS+ in our cohorts over 15 years is approximately 0.45%. VE of 70% against CIS+ with 80% power requires 3357-3189 HPV16/18 vaccine recipients, 3357-3189 other vaccine recipients, and 6714-9567 unvaccinated controls. We have now enrolled 2404 HPV16/18 vaccine recipients, 2404 hepatitis A-vaccine recipients, and 5130 unvaccinated controls. This enrolment in addition to our earlier enrolment in another phase III trial guarantees enough power so that by 2020 we can ultimately provide data on the efficacy of HPV16/18 vaccination against CIS+.
authors.affiliation: University of Tampere, Tampere, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Lehtinen
authors.forename: Dan
authors.initials: D
authors.lastname: Apter
authors.forename: Gary
authors.initials: G
authors.lastname: Dubin
authors.forename: Elise
authors.initials: E
authors.lastname: Kosunen
authors.forename: Rita
authors.initials: R
authors.lastname: Isaksson
authors.forename: Eeva-Leena
authors.initials: EL
authors.lastname: Korpivaara
authors.forename: Laura
authors.initials: L
authors.lastname: Kyhä-Osterlund
authors.forename: Terhi
authors.initials: T
authors.lastname: Lunnas
authors.forename: Tapio
authors.initials: T
authors.lastname: Luostarinen
authors.forename: Lubov
authors.initials: L
authors.lastname: Niemi
authors.forename: Johanna
authors.initials: J
authors.lastname: Palmroth
authors.forename: Tiina
authors.initials: T
authors.lastname: Petäjä
authors.forename: Sirpa
authors.initials: S
authors.lastname: Rekonen
authors.forename: Susanna
authors.initials: S
authors.lastname: Salmivesi
authors.forename: Mari
authors.initials: M
authors.lastname: Siitari-Mattila
authors.forename: Sofia
authors.initials: S
authors.lastname: Svartsjö
authors.forename: Leena
authors.initials: L
authors.lastname: Tuomivaara
authors.forename: Marjo
authors.initials: M
authors.lastname: Vilkki
authors.forename: Eero
authors.initials: E
authors.lastname: Pukkala
authors.forename: Jorma
authors.initials: J
authors.lastname: Paavonen
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D022362:Hepatitis A Vaccines / Q000627:therapeutic use; D052162:Human papillomavirus 16 / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000276:immunology*; D006801:Humans; D032521:Immunity, Herd; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines; D012042:Registries; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014765:Viral Vaccines / Q000627:therapeutic use*; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000517:prevention & control / Q000821:virology
chemical_list: D022362:Hepatitis A Vaccines; D053918:Papillomavirus Vaccines; D014765:Viral Vaccines