HPV-16/18 AS04-Adjuvanted Vaccine Shows High Efficacy Against Cervical Neoplasia

The two human papillomavirus (HPV) vaccines currently available were licensed based on trials showing protection against HPV infection and cervical intraepithelial neoplasia grade 2 or greater (CIN 2+), which may be a precursor to invasive cervical cancer. Two research groups now report 4-year end-of-study data from PATRICIA — a manufacturer-funded, multinational, double-blind trial of one of these preparations (HPV-16/18 AS04-adjuvanted vaccine; Cervarix). In this trial, healthy women aged 15 to 25 with six or fewer lifetime sexual partners were randomized to receive either HPV or hepatitis A vaccine at 0, 1, and 6 months. Gynecological examinations were performed, and cervical specimens obtained, at baseline and periodically thereafter.

Lehtinen and colleagues assessed vaccine efficacy against CIN 3+ (an immediate precursor to invasive cervical cancer) and adenocarcinoma in situ in two groups: the total vaccinated cohort (TVC; all women who received ≥1 vaccine dose) and the TVC-naive (women who received ≥1 vaccine dose and who, at baseline, had negative cytology, were HPV DNA negative for all 14 HPV types tested for, and were seronegative for HPV-16 and HPV-18). Vaccine efficacy against adenocarcinoma in situ was 76.9% in the TVC and 100% in and TVC-naive group; efficacy against all CIN 3+ (irrespective of HPV type in the lesion) was 45.6% and 93.2%, respectively. In the TVC, vaccine efficacy against CIN 3+ was highest in the youngest age group (15–17 years) and progressively declined in older age groups, whereas in the TVC-naive group, efficacy was >90% in all age groups. Antibody concentrations against HPV-16 and HPV-18 remained high throughout the 48 months. The incidence of serious adverse events was similar between the study vaccine and control groups.

Wheeler and colleagues assessed cross-protection against 12 nonvaccine oncogenic HPV types, which together account for approximately 30% of cervical cancers. Their analysis involved three cohorts: according-to-protocol for efficacy (ATP-E; women who at baseline were not infected with the HPV type under analysis and who received all 3 vaccine doses), TVC-naive, and TVC. In the ATP-E cohort, vaccine efficacy against the composite of 12 nonvaccine HPV types was 46.8% for CIN 2+ and 73.8% for CIN 3+. In analyses excluding cases with HPV-16 and HPV-18 coinfection, efficacy was 24.1% and 62.1%, respectively. Efficacy against CIN 3+ associated with the composite of 12 nonvaccine HPV types was higher in the TVC-naive group (91.4%) — and lower in the TVC (47.5%) — than in the ATP-E cohort. The vaccine showed cross-protective efficacy against 6-month persistent infection and CIN 2+ associated with four individual nonvaccine oncogenic types: HPV-33, HPV-31, HPV-45, and HPV-51.