Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland

In this article, the author offers a concise, practical summary of the research findings reported in Paavonen J, Naud P, Salmerón J, et al; the HPV PATRICIA study group. Efficacy 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. Lancet. 2009;374(9686):301-314.

Key research findings

● The HPV-16/18 AS04-adjuvanted vaccine is highly efficacious against CIN2+ associated with HPV 16/18 and nonvaccine oncogenic HPV types

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● The vaccine shows substantial overall efficacy in cohorts relevant to universal mass vaccination and catch-up programs

● The safety profile of the vaccine is favorable and the vaccine is well tolerated

The final analysis of the Papilloma Trial Against Cancer in Young Adults) study shows that the HPV-16/18 AS04-adjuvanted vaccine (Cervarix, GlaxoSmithKline) has high efficacy against the lesions that can eventually lead to cervical cancer. The vaccine also shows crossprotective efficacy against other oncogenic HPV types closely related to HPV-16/18. Furthermore, the vaccine has demonstrated efficacy in women and girls likely to benefit from universal mass vaccination and catch-up programs. The findings were recently reported in The Lancet.1

In the PATRICIA study, females aged 15 to 25 years were randomly assigned to receive the HPV- 16/18 vaccine Cervarix (vaccine) or a hepatitis A vaccine (control). The primary end point was to assess vaccine efficacy against cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Details on the collection of samples and other specifics were previously published.2 Results from 3 cohorts were considered as part of the final analysis. The according-to-protocol for efficacy (ATP-E) cohort included all participants who received 3 vaccine doses (at 0, 1, and 6 months), had normal or low-grade cytology at baseline, complied with the protocol, and were evaluable for the primary end point of CIN2+ (vaccine recipients = 8093, controls = 8069). The total vaccinated cohort (TVC) represented the young sexually active population and included all participants who received at least 1 vaccine dose regardless of their baseline HPV status (vaccine recipients = 9319, controls = 9325). The TVCnaïve cohort represented participants who have not yet had sex and who had no evidence of oncogenic HPV infection at baseline (vaccine recipients = 5822, controls = 5819).

The mean follow-up was slightly less than 3 years after the third dose. In the primary analysis, which considered protection against CIN2+ that was associated with HPV-16/18, vaccine efficacy was 93%. In another analysis, which assigned the cause of lesions infected with multiple oncogenic HPV types (according to a type assignment algorithm) to a single type, vaccine efficacy was 98%. When the HPV type detected in the lesion was not considered in the analysis, vaccine efficacy was 30% in the TVC and 70% in the TVC-naive. Corresponding values against CIN3+ (the immediate precancer of invasive cervical cancer) were 33% and 87% in the TVC and TVC-naïve cohorts, respectively, an indication that HPV-16/18 plays a larger role in CIN3+. CIN3+ is considered to be a more reliable end point than CIN2+. Longer follow-up was required to observe the vaccine’s effect on CIN2+ lesions resulting from newly acquired infections because no change in CIN2+ lesions derived from prevalent infections or low-grade lesions would be anticipated with the vaccine. Delayed separation of the Kaplan- Meier curves showing the cumulative incidences of CIN2+ in the study population support this finding (see Figure).

Figure. Cumulative Incidence of Cervical Intraepithelial Neoplasia Grade 2 or More (CIN2+) Regardless of Human Papillomavirus (HPV) DNA Status or Serostatus at Baseline (Total Vaccinated Cohort) (A) Associated with HPV-16/18 and (B) Irrespective of HPV DNA in the Lesion.