Post-hoc analysis from phase III trials of human papillomavirus vaccines: considerations on impact on non-vaccine types

Abstract

Background: Substantial heterogeneity has been reported in efficacy against high-grade cervical intraepithelial neoplasia (CIN) irrespective of HPV type in phase III results for bivalent and quadrivalent human papillomavirus virus (HPV) vaccines (AS04-HPV and qHPV). Real-world data recently confirmed a very high overall impact of AS04-HPV, supporting the validity of the observed heterogeneity. To explore the reasons for heterogeneous efficacy, we assessed vaccine impact on high-grade lesions not caused by vaccine types. Research methods: We extracted case counts of CIN lesions containing (1) at least one vaccine HPV type, (2) at least one vaccine HPV type and a high-risk non-vaccine type (co-infections) and (3) no vaccine types (non-vaccine or no high-risk HPV types). Based on these, Phase III cross-protective efficacies were estimated with exclusion (3) and with inclusion (2 and 3) of co-infections. Results: Cross-protective efficacy of AS04-HPV against CIN3 lesions ranges from 81.3% (95%CI: 34.7;96.5) (excluding co-infections) to 88.5% (95%CI:62.4;97.8) (including co-infections). For qHPV the efficacy ranges from −58.7% (95%CI: −180.5;8.5) (excluding co-infections) to 13.1% (95%CI: −39.0;45.9) (including co-infections). Conclusions: Heterogenous overall efficacy against CIN3 between AS04-HPV and qHPV is driven by differential efficacy against lesions that do not contain vaccine types, which may be related to the impact of different adjuvants on the immune response.

Keywords

• as04-adjuvanted hpv-16/18 vaccine
• cervical cancer
• cervical intraepithelial neoplasia
• cross-protection
• human papillomavirus