- 作者：Dr ; Prof Cosette M Wheeler ; PhDa ; cwheeler@salud.unm.edu ; Xavier Castellsagué ; PhDb ; Prof Suzanne M Garland ; FRCPAc ; Anne Szarewski ; PhDd ; Prof Jorma Paavonen ; MDe ; Prof Paulo Naud ; PhDf ; Prof Jorge Salmeró ; n ; PhDg ; Prof Song-Nan Chow ; MDh ; Dan Apter ; MDi ; Prof Henry Kitchener ; MDj ; Jú ; lio C Teixeira ; MDk ; S Rachel Skinner ; PhDl ; Prof Unnop Jaisamrarn ; MDm ; Prof Genara Limson ; MDn ; Prof Barbara Romanowski ; MDo ; Prof Fred Y Aoki ; MDp ; Prof Tino F Schwarz ; MDq ; Prof Willy A J Poppe ; PhDr ; F Xavier Bosch ; PhDb ; Diane M Harper ; MDs ; Warner Huh ; MDt ; Karin Hardt ; PhDu ; Toufik Zahaf ; PhDu ; Dominique Descamps ; MDu ; Frank Struyf ; MDu ; Gary Dubin ; MDv ; Prof Matti Lehtinen ; PhDw ; for the HPV PATRICIA Study Group&Dagger ;
- 刊名：Lancet Oncology
- 出版年：2012
- 出版时间：January 2012
- 年：2012
- 卷：13
- 期：1
- 页码：100-110
- 全文大小：220 K
Summary
Background
We evaluated the efficacy of the human papillomavirus HPV-16/18 AS04-adjuvanted vaccine against non-vaccine oncogenic HPV types in the end-of-study analysis after 4 years of follow-up in PATRICIA (PApilloma TRIal against Cancer In young Adults).Methods
Healthy women aged 15-25 years with no more than six lifetime sexual partners were included in PATRICIA irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to HPV-16/18 vaccine or a control hepatitis A vaccine, via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The study was double-blind. The primary endpoint of PATRICIA has been reported previously; the present analysis evaluates cross-protective vaccine efficacy against non-vaccine oncogenic HPV types in the end-of-study analysis. Analyses were done for three cohorts: the according-to-protocol cohort for efficacy (ATP-E; vaccine n=8067, control n=8047), total vaccinated HPV-naive cohort (TVC-naive; no evidence of infection with 14 oncogenic HPV types at baseline, approximating young adolescents before sexual debut; vaccine n=5824, control n=5820), and the total vaccinated cohort (TVC; all women who received at least one vaccine dose, approximating catch-up populations that include sexually active women; vaccine n=9319, control=9325). Vaccine efficacy was evaluated against 6-month persistent infection, cervical intraepithelial neoplasia grade 2 or greater (CIN2+) associated with 12 non-vaccine HPV types (individually or as composite endpoints), and CIN3+ associated with the composite of 12 non-vaccine HPV types. This study is registered with , number .
Findings
Consistent vaccine efficacy against persistent infection and CIN2+ (with or without HPV-16/18 co-infection) was seen across cohorts for HPV-33, HPV-31, HPV-45, and HPV-51. In the most conservative analysis of vaccine efficacy against CIN2+, where all cases co-infected with HPV-16/18 were removed, vaccine efficacy was noted for HPV-33 in all cohorts, and for HPV-31 in the ATP-E and TVC-naive. Vaccine efficacy against CIN2+ associated with the composite of 12 non-vaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), with or without HPV-16/18 co-infection, was 46¡¤8 % (95 % CI 30¡¤7-59¡¤4) in the ATP-E, 56¡¤2 % (37¡¤2-69¡¤9) in the TVC-naive, and 34¡¤2 % (20¡¤4-45¡¤8) in the TVC. Corresponding values for CIN3+ were 73¡¤8 % (48¡¤3-87¡¤9), 91¡¤4 % (65¡¤0-99¡¤0), and 47¡¤5 % (22¡¤8-64¡¤8).
Interpretation
Data from the end-of-study analysis of PATRICIA show cross-protective efficacy of the HPV-16/18 vaccine against four oncogenic non-vaccine HPV types¡ªHPV-33, HPV-31, HPV-45, and HPV-51¡ªin different trial cohorts representing diverse groups of women.
Funding
GlaxoSmithKline Biologicals.