Human papilloma virus vaccines

Abstract

Benign and malignant disease caused by HPV (human papillomavirus) constitutes a global public health problem. Genital warts are the commonest viral sexually transmitted infection and 5 % of all cancers are HPV associated. The unfolding of the HPV story started in the 1970’s with the recognition that HPVs were a large family of viruses that included a subset of types that caused cancer, particularly cancer of the cervix, a disease that kills 250,000 women each year. It has resulted in the development of two prophylactic virus like particle (VLP) vaccines using sophisticated recombinant molecular techniques and protein expression. Both vaccines target infection by the oncogenic HPV’s 16 and 18 and one also targets the low risk HPVs 6 and 11 that cause genital and laryngeal warts. These vaccines are now included in the national immunisation programmes in many countries and population effectiveness in women is being demonstrated in those countries with high vaccine coverage. Since HPV associated cancers in men are increasing in incidence an issue of contemporary debate is extending HPV vaccination to adolescent boys. HPV VLP vaccines have a good safety profile and national and international authorities endorse this. Safety has been assessed in the randomised controlled trials and continues to be monitored by robust pharmacovigilance post licensure using both passive and active vaccine surveillance. HPV vaccines are highly immunogenic generating serum neutralising antibody that persists for at least 9 years with a robust recall response after antigen challenge at 60 months post vaccination. At present the assumption is that the protection achieved by these vaccines against HPV induced disease is mediated via serum neutralising IgG and this is consistent with what is known of the mechanism of HPV infection in the genital tract. Emerging evidence shows that very low antibody concentrations are protective but at the present there is no immune correlate of protection, disease prevention remains the only measure of the effectiveness of HPV vaccines.