Immune control of human papillomavirus (HPV) associated anogenital disease and potential for vaccination

Abstract

This review discusses: (1) immune mechanisms relevant to the natural control of a human papillomavirus (HPV) infection; (2) viral strategies to evade or subvert immune attack; (3) the significance of immune escape as a feature of the evolution of invasive cancer; (4) vaccine strategies for prevention and/or therapy. HPV infection and associated malignancy can induce humoral and cellular immunity to capsid and oncogene viral proteins, but it is not always clear whether such responses are a consequence of the disease rather than the resolving factor(s). Prophylactic strategies are utilising virus-like particles (VLP) composed of the L1 viral capsid protein to induce neutralising antibodies, while therapeutic approaches are aimed at generating specific T cells targeted at the viral E6 and/or E7 oncogenes. Thus far, HPV VLP vaccines have proved clinically efficacious in the early clinical trials to prevent infection. Different types of therapeutic vaccines including peptide, protein, DNA or viral vector encoded have proved safe and immunogenic in patients, although there is often no correlation with clinical outcome. Understanding the equilibrium between viral and immunological factors will be important in providing the appropriate tools to evoke effective prophylactic and therapeutic immunity. It seems likely that combined prophylactic and therapeutic vaccine approaches could offer the best prospect for any significant reduction in death from cervical cancer worldwide.