A review of human papillomavirus vaccines: from basic science to clinical trials

Human papillomavirus (HPV) infection leads to a spectrum of disease from genital warts to precancerous lesions to cervical and anal cancer and is a worldwide public health problem of epidemic proportions. Unique to HPV-related neoplasia, the presence of specific viral antigens such as the L1 capsid structural protein and the oncoproteins E6 and E7 provide opportunities for vaccine therapy. Although difficult to precisely define, the natural immune response to HPV is vitally important and defects in cell mediated immunity correlate with increased risk of disease and cancer. In preclinical animal models, both prophylactic and therapeutic vaccines have effectively induced HPV-specific cell mediated immune responses protecting animals from viral challenge or eliminating established tumors. Most prophylactic vaccines are virus-like particles (VLP) composed of the L1 structural protein. Phase I trials have demonstrated safety and immunogenicity, but limited efficacy data are available. Therapeutic vaccine trials are reviewed including E6 and E7 vaccines comprised of peptides, fusion proteins, encapsulated plasmid DNA, and recombinant vaccinia virus. All of the vaccines appear to be safe, well tolerated, and preliminary data indicates that most are clinically effective. Multiple trials are in progress and more mature data are expected within the next few years.