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Open Access Publications from the University of California

Efficacy of the AS04-adjuvanted HPV-16/18 vaccine: Pooled analysis of the Costa Rica Vaccine and PATRICIA randomized controlled trials.

  • Author(s): Tota, Joseph E
  • Struyf, Frank
  • Sampson, Joshua N
  • Gonzalez, Paula
  • Ryser, Martin
  • Herrero, Rolando
  • Schussler, John
  • Karkada, Naveen
  • Rodriguez, Ana Cecilia
  • Folschweiller, Nicolas
  • Porras, Carolina
  • Schiffman, Mark
  • Schiller, John T
  • Quint, Wim
  • Kreimer, Aimée R
  • Wheeler, Cosette M
  • Hildesheim, Allan
  • Costa Rica Vaccine Trial
  • PATRICIA study
  • et al.

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+.

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