Show simple item record

dc.contributor.authorHuh, WKen_US
dc.contributor.authorJoura, EAen_US
dc.contributor.authorGiuliano, ARen_US
dc.contributor.authorIversen, O-Een_US
dc.contributor.authorde Andrade, RPen_US
dc.contributor.authorAult, KAen_US
dc.contributor.authorBartholomew, Den_US
dc.contributor.authorCestero, RMen_US
dc.contributor.authorFedrizzi, ENen_US
dc.contributor.authorHirschberg, ALen_US
dc.contributor.authorMayrand, M-Hen_US
dc.contributor.authorRuiz-Sternberg, AMen_US
dc.contributor.authorStapleton, JTen_US
dc.contributor.authorWiley, DJen_US
dc.contributor.authorFerenczy, Aen_US
dc.contributor.authorKurman, Ren_US
dc.contributor.authorRonnett, BMen_US
dc.contributor.authorStoler, MHen_US
dc.contributor.authorCuzick, Jen_US
dc.contributor.authorGarland, SMen_US
dc.contributor.authorKjaer, SKen_US
dc.contributor.authorBautista, OMen_US
dc.contributor.authorHaupt, Ren_US
dc.contributor.authorMoeller, Een_US
dc.contributor.authorRitter, Men_US
dc.contributor.authorRoberts, CCen_US
dc.contributor.authorShields, Cen_US
dc.contributor.authorLuxembourg, Aen_US
dc.date.accessioned2017-09-22T16:36:53Z
dc.date.available2017-06-15en_US
dc.date.issued2017-11-11en_US
dc.date.submitted2017-09-07T10:24:07.491Z
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/25830
dc.description.abstractBACKGROUND: Primary analyses of a study in young women aged 16-26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18 antibody responses when compared with quadrivalent HPV (qHPV; HPV 6, 11, 16, and 18) vaccine. We aimed to report efficacy of the 9vHPV vaccine for up to 6 years following first administration and antibody responses over 5 years. METHODS: We undertook this randomised, double-blind, efficacy, immunogenicity, and safety study of the 9vHPV vaccine study at 105 study sites in 18 countries. Women aged 16-26 years old who were healthy, with no history of abnormal cervical cytology, no previous abnormal cervical biopsy results, and no more than four lifetime sexual partners were randomly assigned (1:1) by central randomisation and block sizes of 2 and 2 to receive three intramuscular injections over 6 months of 9vHPV or qHPV (control) vaccine. All participants, study investigators, and study site personnel, laboratory staff, members of the sponsor's study team, and members of the adjudication pathology panel were masked to vaccination groups. The primary outcomes were incidence of high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, invasive cervical carcinoma), vulvar disease (vulvar intraepithelial neoplasia grade 2/3, vulvar cancer), and vaginal disease (vaginal intraepithelial neoplasia grade 2/3, vaginal cancer) related to HPV 31, 33, 45, 52, and 58 and non-inferiority (excluding a decrease of 1·5 times) of anti-HPV 6, 11, 16, and 18 geometric mean titres (GMT). Tissue samples were adjudicated for histopathology diagnosis and tested for HPV DNA. Serum antibody responses were assessed by competitive Luminex immunoassay. The primary evaluation of efficacy was a superiority analysis in the per-protocol efficacy population, supportive efficacy was analysed in the modified intention-to-treat population, and the primary evaluation of immunogenicity was a non-inferiority analysis. The trial is registered with ClinicalTrials.gov, number NCT00543543. FINDINGS: Between Sept 26, 2007, and Dec 18, 2009, we recruited and randomly assigned 14 215 participants to receive 9vHPV (n=7106) or qHPV (n=7109) vaccine. In the per-protocol population, the incidence of high-grade cervical, vulvar and vaginal disease related to HPV 31, 33, 45, 52, and 58 was 0·5 cases per 10 000 person-years in the 9vHPV and 19·0 cases per 10 000 person-years in the qHPV groups, representing 97·4% efficacy (95% CI 85·0-99·9). HPV 6, 11, 16, and 18 GMTs were non-inferior in the 9vHPV versus qHPV group from month 1 to 3 years after vaccination. No clinically meaningful differences in serious adverse events were noted between the study groups. 11 participants died during the study follow-up period (six in the 9vHPV vaccine group and five in the qHPV vaccine group); none of the deaths were considered vaccine-related. INTERPRETATION: The 9vHPV vaccine prevents infection, cytological abnormalities, high-grade lesions, and cervical procedures related to HPV 31, 33, 45, 52, and 58. Both the 9vHPV vaccine and qHPV vaccine had a similar immunogenicity profile with respect to HPV 6, 11, 16, and 18. Vaccine efficacy was sustained for up to 6 years. The 9vHPV vaccine could potentially provide broader coverage and prevent 90% of cervical cancer cases worldwide. FUNDING: Merck & Co, Inc.en_US
dc.description.sponsorshipMerck & Co, Inc (Kenilworth, NJ, USA)en_US
dc.format.extent2143 - 2159en_US
dc.languageengen_US
dc.language.isoenen_US
dc.relation.ispartofLanceten_US
dc.subjectAdolescenten_US
dc.subjectAdulten_US
dc.subjectAntibodies, Viralen_US
dc.subjectDose-Response Relationship, Drugen_US
dc.subjectDouble-Blind Methoden_US
dc.subjectFemaleen_US
dc.subjectFollow-Up Studiesen_US
dc.subjectHuman Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18en_US
dc.subjectHuman papillomavirus 6en_US
dc.subjectHumansen_US
dc.subjectImmunoassayen_US
dc.subjectImmunogenicity, Vaccineen_US
dc.subjectInjections, Intramuscularen_US
dc.subjectPapillomavirus Infectionsen_US
dc.subjectPatient Complianceen_US
dc.subjectPatient Safetyen_US
dc.subjectPrimary Preventionen_US
dc.subjectTreatment Outcomeen_US
dc.subjectUterine Cervical Neoplasmsen_US
dc.subjectVaccinationen_US
dc.subjectYoung Adulten_US
dc.titleFinal efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial.en_US
dc.typeArticle
dc.rights.holder© 2017 Elsevier Ltd.
dc.identifier.doi10.1016/S0140-6736(17)31821-4en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/28886907en_US
pubs.issue10108en_US
pubs.notesNot knownen_US
pubs.organisational-group/Queen Mary University of London
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Wolfson Institute of Preventive Medicine
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Wolfson Institute of Preventive Medicine/Centre for Cancer Prevention
pubs.organisational-group/Queen Mary University of London/REF
pubs.organisational-group/Queen Mary University of London/REF/REF - SMD - Wolfson
pubs.publication-statusPublisheden_US
pubs.volume390en_US
dcterms.dateAccepted2017-06-15en_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record