Cervarix

Background

Introduction

Cervarix is a recently introduced recombinant bivalent HPV vaccine containing purified viruslike particles of the L1 capsid protein from HPV types 16 and 18 in a formulation with a novel and highly immunogenic proprietary adjuvant.

The Cervarix clinical trial programme

The pre-licensing programme for Cervarix comprised two major clinical trials (a ‘proof-ofconcept’ Phase IIb study and a larger Phase III trial) encompassing some 19,788 women aged

15–25 years.7,9,11,12 The key features of these studies are summarised in Table 1. A further Phase III, community-based, randomised clinicaltrial is currently underway in Costa Rica, which is sponsored by the National Cancer Institute. An interim analysis of this study has reported on the effects of Cervarix in women with pre-existing HPV infections (see below).13 In total, completed and ongoing clinical trials of Cervarix will involve nearly 30,000 women and girls aged between 10 and 55 years.8 In the initial Phase IIb study, vaccine efficacy was evaluated by examining the impact of Cervarix on incident and persistent HPV 16/18 infections in women naïve to 14 different high-risk oncogenic HPV types, including HPV 16 and 18, and who also had normal cervical cytology (Table 1). This study also included an extension phase, which evaluated these same parameters with longer-term follow-up (mean follow-up 47.7 months). Although it is only a surrogate marker for vaccine efficacy against clinical disease, persistent HPV infection can be readily monitored using standard molecular biology techniques thereby providing substantial reproducibility between testing centres, in contrast to the subjective nature of cytological and histological assessments. However, licensing authorities now demand that clinical trials of cervical cancer vaccine also evaluate the incidence of histological lesions of the cervix including the incidence of CIN2+, which is now widely considered to be the most direct correlate of vaccine efficacy in preventing cervical cancer.14 Although the Phase II study evaluated the effect of Cervarix on cytological and histological cervical abnormalities, with extended follow-up of up to 4.5 years, the trial was insufficiently powered to provide firm evidence of vaccine efficacy.

Publications, Contact, Resources and Notes

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