The ability to generate human papillomavirus (HPV) virus-like particles (VLPs) by the synthesis and self-assembly in vitro of the major virus capsid protein L1 has transformed our prospects for preventing both benign and malignant HPV-associated genital disease and, in particular, for significantly reducing the incidence of cervical carcinoma in women. Two HPV L1 VLP vaccines have been developed. Both of these vaccines have been shown to be safe and highly immunogenic, generating high titres of neutralising antibody that persist at measurable levels higher than those measured in natural infections for at least 60 months post-vaccination. This suggests that strong immune memory is generated. At present, the assumption is that the protection achieved by these vaccines against HPV-induced ano-genital pathology is mediated via serum-neutralising IgG. However, since there have been no vaccine failures thus far, immune correlates of protection have not been established. The available evidence is that the immunodominant neutralising antibodies generated in natural infections are type-specific and are not cross-neutralising, although highly homologous HPV pairs share cross-neutralisation epitopes. Cross-reactive and cross-neutralising antibodies are generated in HPV L1 vaccines. At lower concentrations, cross-protection against incident infection has been shown, but the duration of any cross-protection that might be elicited is uncertain. L1 VLP vaccines are prophylactic, not therapeutic, vaccines and for maximal population effectiveness should be delivered before sexual activity begins—that is, to pre-pubertal females (or males). Robust antibody responses have been demonstrated in immunogenicity bridging studies in 9–15-year-old boys and girls. However, social and cultural issues may be important in determining vaccine take-up in the optimal cohort.

Papillomaviruses are small, double-stranded DNA viruses that infect the squamous epithelia (skin and internal mucosae) of both animals and humans. …