Human papillomavirus vaccines: current status and perspectives

Abstract

Human papillomavirus (HPV) infection causes virtually all cases of cervical cancer, the second most common cause of death from cancer among women worldwide. The ability to generate human papillomavirus virus (HPV)-like particles by the synthesis and self-assembly in vitro of the major virus capsid protein L1 has transformed our prospects for preventing cervical carcinoma in women. These particles provide vaccines that are immunogenic and safe. Following preclinical research by laboratories in the nonprofit sector, Merck and GlaxoSmithKline are developing commercial versions of the vaccine. Both vaccines target HPV-16 and HPV-18, which account for approximately 70% of cervical cancer. The Merck vaccine also targets HPV-6 and HPV-11, which account for approximately 90% of external genital warts. Published data from proof of principle trials and preliminary reports from large Phase III efficacy trials suggest strongly that they will protect against persistent HPV infection and cervical intra-epithelial neoplasia. However, the duration of protection provided by these vaccines is not known, the antibody responses induced are probably HPV type specific and immunisation should occur pre-exposure to the virus. Unresolved issues also include the most critical groups to vaccinate and when the vaccine's cost may be low enough for widespread implementation in the developing world, where 80% of cervical cancer occurs. Nevertheless, it may be that an HPV vaccine that protects against the complications of HPV infection such as cervical cancer will be one of the most significant public health initiatives of this decade.