title: Impact of an HPV6/11/16/18 L1 virus-like particle vaccine on progression to cervical intraepithelial neoplasia in seropositive women with HPV16/18 infection.
abstract: The impact of a human papillomavirus (HPV) vaccine on development of cervical intraepithelial neoplasia grade 2-3 or adenocarcinoma in situ (CIN2-3/AIS) in women with ongoing HPV16 or 18 infections prevaccination is reported. Seventeen thousand six-hundred and twenty-two women aged 16-26 were enrolled in 1 of 2 randomized, placebo-controlled, efficacy trials (Protocols 013 and 015). Vaccine or placebo was given at day 1, month 2 and 6. Women were tested for HPV6/11/16/18 DNA and antibodies at day 1. We focus on the subset of women who were seropositive and DNA positive to HPV16 or HPV18 prevaccination. Incidence is expressed as the number of women with an endpoint per 100 person-years-at-risk. In total, 419 vaccine and 446 placebo recipients were both seropositive and DNA positive to HPV16 or HPV18 prevaccination and had at least one follow-up visit. In Protocol 013, the incidence of HPV16/18-related CIN2-3/AIS among these women was 10.9 in the vaccine arm and 7.0 in the placebo arm (vaccine efficacy = -54.9; 95% CI: -181.7, 13.0). In Protocol 015, the incidence of HPV16/18-related CIN2-3/AIS was 5.5 in the vaccine arm and 6.2 in the placebo arm (vaccine efficacy = 12.2%; 95% CI: -29.8, 40.9). These data suggest HPV vaccination neither reduces nor enhances progression to HPV16/18-related high grade cervical lesions, and cervical cytology screening and corresponding management should continue as per local recommendations. Ultimately, population-based surveillance of vaccinated individuals beyond these clinical trials will be required to further address questions regarding the impact of vaccination in women exposed to vaccine HPV types before vaccination.
authors.affiliation: Department of Research, Merck Sharp & Dohme, Corp., Whitehouse Station, NJ, USA. richard_haupt@merck.com
authors.forename: Richard M
authors.initials: RM
authors.lastname: Haupt
authors.forename: Cosette M
authors.initials: CM
authors.lastname: Wheeler
authors.forename: Darron R
authors.initials: DR
authors.lastname: Brown
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Garland
authors.forename: Daron G
authors.initials: DG
authors.lastname: Ferris
authors.forename: Jorma A
authors.initials: JA
authors.lastname: Paavonen
authors.forename: Matti O
authors.initials: MO
authors.lastname: Lehtinen
authors.forename: Marc
authors.initials: M
authors.lastname: Steben
authors.forename: Elmar A
authors.initials: EA
authors.lastname: Joura
authors.forename: Katherine E D
authors.initials: KE
authors.lastname: Giacoletti
authors.forename: David R
authors.initials: DR
authors.lastname: Radley
authors.forename: Margaret K
authors.initials: MK
authors.lastname: James
authors.forename: Alfred J
authors.initials: AJ
authors.lastname: Saah
authors.forename: Heather L
authors.initials: HL
authors.lastname: Sings
mesh_terms: D000293:Adolescent; D000328:Adult; D004279:DNA, Viral / Q000235:genetics; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D052162:Human papillomavirus 16 / Q000276:immunology* / Q000302:isolation & purification; D052161:Human papillomavirus 18 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D030361:Papillomavirus Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000628:therapy* / Q000821:virology; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000628:therapy* / Q000821:virology
chemical_list: D004279:DNA, Viral; D053918:Papillomavirus Vaccines; D058425:Vaccines, Virus-Like Particle