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Lancet. 2009 Jul 25;374(9686):301-14. doi: 10.1016/S0140-6736(09)61248-4. Epub 2009 Jul 6.

Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women.

Collaborators (190)

Denham I, Garland S, Mindel A, O'Sullivan M, Skinner SR, Waddell R, de Carvalho N, Naud P, Teixeira JC, De Sutter P, Poppe WA, Tjalma W, Aoki FY, Diaz-Mitoma F, Dionne M, Ferguson L, Miller M, Papp K, Ramjattan B, Romanowski B, Somani R, Apter D, Astikainen S, Karppa T, Kekki M, Keranen H, Kudjoi N, Kuortti M, Kupari M, Kyha-Osterlund L, Isaksson R, Lehtinen M, Levanen H, Liljamo T, Loonberg K, Niemi L, Paavonen J, Palmroth J, Petaja T, Rekonen S, Romppanen U, Siitari-Mattila M, Tuomivaara L, Vilkki M, Belling KH, Gent T, Grubert T, Harlfinger W, Holst A, Höpker WD, Jensen-El Tobgui S, Merder G, Peters K, Schoenian S, Schulze K, Schwarz T, Wackernagel C, Boselli F, Mojana G, Salmerón J, Benitez G, Crisostomo C, Del Rosario-Raymundo R, Germar MJ, Limson G, Raymundo J, Remollino MC, Villanueva G, Villanueva S, Zamora JD, Zamora L, Bajo J, Bayas J, Campins M, Castellsague X, Castro M, Centeno C, Cruzet F, Rodríguez L, Torné A, Vidart JA, Chow SN, Yu MH, Yuan CC, Huang SC, Ho HN, Chen RJ, Lin HH, Chu TY, Angsuwathana S, Jaisamrarn U, Wilawan K, Abdulhakim E, Cruickshank M, Kitchener H, Lewis D, Pavel I, Robinson J, Szarewski A, Ackerman R, Ault K, Bennett N, Caldwell M, Chambers C, Chatterjee A, Civitarese L, Demars L, De Santis T, Downs L, Ferris D, Fine P, Gall S, Harper D, Hedrick J, Herzig W, Hiraoka M, Huh W, Kamemoto L, Klein T, Koltun W, Kong A, Lalezari J, Lee P, Leeman L, Luber S, Martens M, Michelson J, Nebel W, Peterson C, Pitts K, Rosen J, Rosenfeld W, Scutella M, Seidman L, Sperling M, Sperling R, Stager M, Stapleton J, Swenson K, Thoming C, Twiggs L, Waldbaum A, Wheeler CM, Yardley M, Zbella E, Kiviat N, Klugman KP, Nieminen P, Bergeron C, Eisenstein E, Karron R, Marks R, Nolan T, Tay SK, Albers S, Bollaerts P, Camier A, Colau B, De Breyne A, Genevrois S, Issaka Z, Martens N, Peeters P, Smoes N, Spiessens B, Tavares F, Tonglet A, Vanden-Dunghen S, Vilain AS, Ward KR, Alt E, Iskaros B, Limaye A, Liu-Jarin X, Luff RD, McNeeley M, Provenzano C, Winkler B, Molijn A, Quint W, Struijk L, Van de Sandt M, Van Doorn LJ, Greenacre M, Baronikova S, Zahaf T, David MP, Declerck L, Dupin J, Maroye JL.

Author information

  • 1Department of Obstetrics and Gynaecology, University of Helsinki, Helsinki, Finland. Jorma.Paavonen@hus.fi

Erratum in

  • Lancet. 2010 Sep 25;376(9746):1054.

Abstract

BACKGROUND:

The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections, and associated precancerous lesions in an event-triggered interim analysis of the phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in the final event-driven analysis.

METHODS:

Women (15-25 years) were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC, included all women receiving at least one vaccine dose, regardless of their baseline HPV status; represents the general population, including those who are sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut; vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and DNA negative at baseline and month 6 for the corresponding type (ATP-E). This trial is registered with ClinicalTrials.gov, number NCT00122681.

FINDINGS:

Mean follow-up was 34.9 months (SD 6.4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92.9% (96.1% CI 79.9-98.3) in the primary analysis and 98.1% (88.4-100) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types (ATP-E cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was 30.4% (16.4-42.1) in the TVC and 70.2% (54.7-80.9) in the TVC-naive. Corresponding values against CIN3+ were 33.4% (9.1-51.5) in the TVC and 87.0% (54.9-97.7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54.0% (34.0-68.4; ATP-E). Individual cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in the TVC.

INTERPRETATION:

The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes.

FUNDING:

GlaxoSmithKline Biologicals.

Comment in

PMID:
19586656
[PubMed - indexed for MEDLINE]
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