title: Sustained efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine: final analysis of a long-term follow-up study up to 9.4 years post-vaccination.
abstract: HPV-023 (NCT00518336; ClinicalTrial.gov) is a long-term follow-up of an initial double-blind, randomized (1:1), placebo-controlled study (HPV-001, NCT00689741) evaluating the efficacy against human papillomavirus (HPV)-16/18 infection and associated cyto-histopathological abnormalities, persistence of immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine. Among the women, aged 15-25 years, enrolled in HPV-001 and who participated in the follow-up study HPV-007 (NCT00120848), a subset of 437 women from five Brazilian centers participated in this 36-month long-term follow-up (HPV-023) for a total of 113 months (9.4 years). During HPV-023, anti-HPV-16/18 antibodies were measured annually by enzyme-linked immunosorbent assay (ELISA) and pseudovirion-based neutralisation assay (PBNA). Cervical samples were tested for HPV DNA every 6 months, and cyto-pathological examinations were performed annually. During HPV-023, no new HPV-16/18-associated infections and cyto-histopathological abnormalities occurred in the vaccine group. Vaccine efficacy (VE) against HPV-16/18 incident infection was 100% (95%CI: 66.1, 100). Over the 113 months (9.4 years), VE was 95.6% (86.2, 99.1; 3/50 cases in vaccine and placebo groups, respectively) against incident infection, 100% (84·1, 100; 0/21) against 6-month persistent infection (PI); 100% (61·4, 100; 0/10) against 12-month PI; 97·1% (82.5, 99.9; 1/30) against ≥ ASC-US; 95·0% (68.0, 99.9; 1/18) against ≥ LSIL; 100% (45.2, 100; 0/8) against CIN1+; and 100% (-128.1, 100; 0/3) against CIN2+ associated with HPV-16/18. All vaccinees remained seropositive to HPV-16/18, with antibody titers remaining several folds above natural infection levels, as measured by ELISA and PBNA. There were no safety concerns. To date, these data represent the longest follow-up reported for a licensed HPV vaccine.
authors.affiliation: a Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul; Porto Alegre, Rio Grande do Sul, Brazil Paulo.
authors.forename: Paulo S
authors.initials: PS
authors.lastname: Naud
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Roteli-Martins
authors.forename: Newton S
authors.initials: NS
authors.lastname: De Carvalho
authors.forename: Julio C
authors.initials: JC
authors.lastname: Teixeira
authors.forename: Paola C
authors.initials: PC
authors.lastname: de Borba
authors.forename: Nervo
authors.initials: N
authors.lastname: Sanchez
authors.forename: Toufik
authors.initials: T
authors.lastname: Zahaf
authors.forename: Gregory
authors.initials: G
authors.lastname: Catteau
authors.forename: Brecht
authors.initials: B
authors.lastname: Geeraerts
authors.forename: Dominique
authors.initials: D
authors.lastname: Descamps
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001938:Brazil; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006651:Histocytochemistry; D052162:Human papillomavirus 16 / Q000276:immunology* / Q000302:isolation & purification; D052161:Human papillomavirus 18 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D009500:Neutralization Tests; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*; D014626:Vaginal Smears; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004279:DNA, Viral; D053918:Papillomavirus Vaccines
keywords: HPV-16/18 AS04-adjuvanted vaccine; cervical cancer; efficacy; human papillomavirus (HPV); immunogenicity; long-term protection; pre-cancer; safety