title: High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up.
abstract: Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16-23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrollment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy = 100%; 95% CI:12-100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts.
authors.affiliation: Ludwig Institute for Cancer Research, R Prof Antonio Prudente 109, 01509-010 Sao Paulo, SP, Brazil. llvilla@ludwig.org.br
authors.forename: L L
authors.initials: LL
authors.lastname: Villa
authors.forename: R L R
authors.initials: RL
authors.lastname: Costa
authors.forename: C A
authors.initials: CA
authors.lastname: Petta
authors.forename: R P
authors.initials: RP
authors.lastname: Andrade
authors.forename: J
authors.initials: J
authors.lastname: Paavonen
authors.forename: O-E
authors.initials: OE
authors.lastname: Iversen
authors.forename: S-E
authors.initials: SE
authors.lastname: Olsson
authors.forename: J
authors.initials: J
authors.lastname: Høye
authors.forename: M
authors.initials: M
authors.lastname: Steinwall
authors.forename: G
authors.initials: G
authors.lastname: Riis-Johannessen
authors.forename: A
authors.initials: A
authors.lastname: Andersson-Ellstrom
authors.forename: K
authors.initials: K
authors.lastname: Elfgren
authors.forename: G von
authors.initials: Gv
authors.lastname: Krogh
authors.forename: M
authors.initials: M
authors.lastname: Lehtinen
authors.forename: C
authors.initials: C
authors.lastname: Malm
authors.forename: G M
authors.initials: GM
authors.lastname: Tamms
authors.forename: K
authors.initials: K
authors.lastname: Giacoletti
authors.forename: L
authors.initials: L
authors.lastname: Lupinacci
authors.forename: R
authors.initials: R
authors.lastname: Railkar
authors.forename: F J
authors.initials: FJ
authors.lastname: Taddeo
authors.forename: J
authors.initials: J
authors.lastname: Bryan
authors.forename: M T
authors.initials: MT
authors.lastname: Esser
authors.forename: H L
authors.initials: HL
authors.lastname: Sings
authors.forename: A J
authors.initials: AJ
authors.lastname: Saah
authors.forename: E
authors.initials: E
authors.lastname: Barr
mesh_terms: D000293:Adolescent; D000328:Adult; D052685:Alphapapillomavirus / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood; D003218:Condylomata Acuminata / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D002578:Uterine Cervical Dysplasia / Q000517:prevention & control; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*; D014626:Vaginal Smears; D014771:Virion / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18