title: Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical intraepithelial neoplasia and cervical infection in young Japanese women.
abstract: In this open, extended follow-up study (NCT00929526, Clinicaltrials.gov), we evaluated the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine efficacy, immunogenicity and safety up to 4 years after first vaccination in Japanese women aged 20-25 years. In the initial randomized, double-blind study (NCT00316693), 1040 women received the study vaccine or hepatitis A control vaccine; 752 women were included in the follow-up study. In women from the according-to-protocol efficacy cohort (ATP-E), who were initially seronegative for the HPV type analyzed, no cervical intraepithelial neoplasia (CIN) grade 1 or greater (CIN1+) cases associated with HPV-16/18 were reported in the HPV group, while in the control group, 5 cases were identified in extended follow-up analyses (vaccine efficacy [VE] 100% [95% CI: -3.7-100]) and 8 cases in combined initial and follow-up studies analyses (VE 100% [42.2-100]). In the ATP-E, VE against CIN1+ and CIN2+ associated with high-risk HPV types reached 66.4% (21.6-87.1) and 83.0% (22.1-98.2) in extended follow-up analyses, and 63.4% (28.8-82.3) and 77.3% (30.4-94.4) in analyses of combined studies, respectively. During the 4-year period, protection against CIN1+ and CIN2+, irrespective of the HPV type, was 56.7% (32.8-72.6) and 54.9% (20.5-75.3) in women receiving ≥1 vaccine dose, regardless of baseline serostatus (total vaccinated cohort [TVC]) and 61.0% (11.8-84.2) and 73.9% (1.1-95.3) in women naïve to HPV infection at baseline (TVC-naïve), respectively. The high VE observed in Japanese women, accompanied by a sustained immune response and a clinically acceptable safety profile, support findings of large, international trials.
authors.affiliation: a Department of Obstetrics and Gynaecology; Jichi Medical University; Saitama Medical Center; Saitama, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Konno
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Marie
authors.initials: M
authors.lastname: Okutani
authors.forename: Wim
authors.initials: W
authors.lastname: Quint
authors.forename: Pemmaraju
authors.initials: P
authors.lastname: V Suryakiran
authors.forename: Lan
authors.initials: L
authors.lastname: Lin
authors.forename: Frank
authors.initials: F
authors.lastname: Struyf
mesh_terms: D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage*; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D052162:Human papillomavirus 16 / Q000276:immunology; D052161:Human papillomavirus 18 / Q000276:immunology; D006801:Humans; D007564:Japan; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives*; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000517:prevention & control*
chemical_list: C532963:ASO4 mixture; D000914:Antibodies, Viral; D008050:Lipid A; D053918:Papillomavirus Vaccines; D000536:Aluminum Hydroxide
keywords: HPV-16/18 AS04-adjuvanted vaccine; Japan; cervical cancer; efficacy; human papillomavirus; safety