Fast track — ArticlesEfficacy 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
Introduction
Human papillomavirus (HPV) vaccines are now licensed in more than 100 countries. National and regional immunisation programmes aimed at young adolescent girls have been widely implemented, and include catch-up programmes in some countries up to the age of 18 years or older.1 The HPV-16/18 vaccine is adjuvanted with AS04 (consisting of aluminium hydroxide and 3-O-desacyl-4′-monophosphoryl lipid A), shown to enhance the vaccine's immunogenicity.2 This adjuvanted vaccine has been shown to be highly immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections and associated precancerous lesions, in an event-triggered interim analysis in our phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA),3 and other trials.4, 5, 6, 7 Additionally, the vaccine has been shown to protect not only against HPV-16 and HPV-18 but also against other non-vaccine oncogenic HPV types.3, 5, 8
We now present the final event-driven analysis, which includes cases accrued over a follow-up of about 3 years. As well as a further assessment of the vaccine efficacy against persistent infection and cervical intraepithelial neoplasia grade 2+ (CIN2+) associated with HPV-16/18 that was already noted in the interim analysis, we also assessed the efficacy of the vaccine against CIN3+ lesions, and infections and lesions caused by non-vaccine oncogenic HPV types in the final event-driven analysis. To further explore the potential public health effect of the HPV-16/18 AS04-adjuvanted vaccine, we did efficacy analyses in a broad population of sexually active young women that included a large proportion with evidence of current or previous HPV infection at the start of the trial. Additionally, we did analyses in a population with no evidence of exposure to 14 oncogenic HPV types that represents young adolescent girls before sexual debut (the primary target population for current public health vaccination programmes).
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Participants
Healthy women aged 15–25 years at the time of first vaccination were enrolled in the trial between May, 2004, and June 2005, at 135 centres in 14 countries in Asia Pacific, Europe, Latin America, and North America. Women who reported no more than six lifetime sexual partners before study enrolment, agreed to using adequate contraception over the vaccination period, and had an intact cervix were eligible for inclusion. Women were excluded if they had a history of colposcopy, were pregnant or
Results
A total of 18 644 women were included in the TVC. Figure 2 shows the distribution of the participants. A total of 17 106 women (92%) completed the full vaccination schedule. Table 1 shows the demographic and baseline characteristics of the three cohorts. The characteristics of women in the TVC-E and ATP cohort for immunogenicity were similar (data not shown). A substantial proportion of women (n=4828, 26%) had evidence of past or current infection with HPV-16/18 at baseline (table 1), but only
Discussion
The final event-triggered analysis of our trial confirmed the high efficacy of the HPV-16/18 AS04-adjuvanted vaccine in the prevention of CIN2+ lesions associated with HPV-16/18. The present analysis adds important information about the prevention of CIN2+ associated with HPV-16 and HPV-18 individually, and also the prevention of CIN3+, the immediate precursor of invasive cervical cancer (ATP-E cohort analysis). We were also able to confirm and add to our previous findings of cross-protection
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