Efficacy of the AS04-adjuvanted HPV-16/18 vaccine: Pooled analysis of the Costa Rica Vaccine and PATRICIA randomized controlled trials
Menée à partir des données de deux essais portant au total sur 12 550 femmes, cette étude évalue l'efficacité d'un vaccin ciblant les papillomavirus humains de type 16 et de type 18 pour réduire le risque d'infection par les autres types de papillomavirus humains ainsi que l'incidence des lésions cervicales
Résumé en anglais
Background : The AS04-adjuvanted HPV-16/18 (AS04-HPV-16/18) vaccine provides excellent protection against targeted HPV types and a variable degree of cross-protection against others, including types 6/11/31/33/45. High efficacy against any cervical intraepithelial neoplasia grade 3 or greater (CIN3+; >90%) suggests lower levels of protection may exist for a wide-range of oncogenic HPV types, which is difficult to quantify in individual trials. Pooling individual-level data from two randomized controlled trials (RCTs), we aimed to evaluate AS04-HPV-16/18 vaccine efficacy against incident HPV infections and cervical abnormalities.
Methods : Data were available from the Costa Rica Vaccine Trial (CVT; NCT00128661) and PATRICIA trial (NCT00122681) – two large-scale, double-blind RCTs of the AS04-HPV-16/18 vaccine. Primary analyses focused on disease-free women with no detectable cervicovaginal HPV at baseline.
Results : 12,550 women were included in our primary analyses (HPV arm=6,271; control arm=6,279). Incidence of six month persistent oncogenic/non-oncogenic infections, excluding known/accepted protected types 6/11/16/18/31/33/45 (focusing on 34/35/39/40/42/43/44/51/52/53/54/56/58/59/66/68/73/70/74), was statistically significantly lower in the HPV arm than in the control arm (efficacy=9.9%, 95% Confidence Interval [CI] 1.7%-17.4%). Statistically significant efficacy (p < 0.05) was observed for individual oncogenic types 16/18/31/33/45/52 and non-oncogenic types 6/11/53/74. Efficacy against cervical abnormalities (all types) increased with severity, ranging from 27.7% (95% CI 21.7%-33.3%) to 58.7% (95% CI 34.1%-74.7%) for cytologic outcomes (low-grade squamous intraepithelial neoplasia lesion or greater, and high-grade squamous intraepithelial neoplasia lesion or greater, respectively) and 66.0% (95% CI 54.4%-74.9%) to 87.8% (95% CI 71.1%-95.7%) for histologic outcomes (CIN2+ and CIN3+, respectively). Comparing CVT and PATRICIA results, there was no evidence of heterogeneity, except for type 51 (efficacy=-28.6% and 20.7%, respectively; two-sided p = 0.03).
Conclusions : The AS04-HPV-16/18 vaccine provides some additional cross-protection beyond established protected types, which partially explains the high efficacy against CIN3+.
