title: Understanding long-term protection of human papillomavirus vaccination against cervical carcinoma: Cancer registry-based follow-up.
abstract: Phase III clinical trials of human papilloma virus (HPV) vaccination have shown ≥95% efficacy against HPV16/18 associated cervical intraepithelial neoplasia (CIN) Grade 2/3. Long-term surveillance is, however, needed to determine the overall vaccine efficacy (VE) against CIN3 and invasive cervical carcinoma (ICC). During population-based recruitment between September 2002 and March 2003, 1,749 16- to 17-year old Finns participated in a multi-national randomized Phase III HPV6/11/16/18 vaccine (FUTURE II) trial for the determination of VE against HPV16/18 positive CIN2/3. The passive follow-up started at the country-wide, population-based Finnish Cancer Registry (FCR) six months after the active follow-up and voluntary cross-vaccination in April 2007. A cluster randomized, population-based reference cohort of 15,744 unvaccinated, originally 18-19 year old Finns was established in two phases in 2003 and 2005 after the FUTURE II recruitment. We linked these cohorts with the FCR in 2007-2011 (HPV vaccine and placebo cohorts) and 2006-2010 and 2008-2012 (unvaccinated reference cohorts 1 and 2) to compare their incidences of CIN3 and ICC. The four years passive follow-up resulted in 3,464, 3,444 and 62,876 person years for the HPV6/11/16/18, original placebo and reference cohorts, after excluding cases discovered during the clinical follow-up and individuals not at risk. The numbers of CIN3 and ICC cases identified were 0 and 0, 3 and 0, 59 and 3 for the HPV6/11/16/18, placebo and the unvaccinated reference cohorts. The corresponding CIN3 incidence rates were 0/100,000 (95% confidence interval 0.0-106.5), 87.1/100,000 (95% CI 17.9-254.5) and 93.8/100,000 (95% CI 71.4-121), respectively. Long-term surveillance up to 8 years (and longer) post vaccination of the HPV6/11/16/18 vaccine and placebo cohorts, and the unvaccinated reference cohort (not exposed to interventions) for the most stringent efficacy end-points by passive cancer registry-based follow-up is feasible.
authors.affiliation: School of Health Sciences, University of Tampere, Tampere, Finland. mohsin.rana@uta.fi
authors.forename: Muhammad Mohsin
authors.initials: MM
authors.lastname: Rana
authors.forename: Heini
authors.initials: H
authors.lastname: Huhtala
authors.forename: Dan
authors.initials: D
authors.lastname: Apter
authors.forename: Tiina
authors.initials: T
authors.lastname: Eriksson
authors.forename: Tapio
authors.initials: T
authors.lastname: Luostarinen
authors.forename: Kari
authors.initials: K
authors.lastname: Natunen
authors.forename: Jorma
authors.initials: J
authors.lastname: Paavonen
authors.forename: Eero
authors.initials: E
authors.lastname: Pukkala
authors.forename: Matti
authors.initials: M
authors.lastname: Lehtinen
mesh_terms: D000293:Adolescent; D000328:Adult; D019496:Cancer Vaccines / Q000276:immunology*; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D027383:Papillomaviridae / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000276:immunology*; D011159:Population Surveillance; D012042:Registries; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control*; D014611:Vaccination; D055815:Young Adult
chemical_list: D019496:Cancer Vaccines; D053918:Papillomavirus Vaccines