'High risk' genotypes of the human papillomavirus (HPV), particularly HPV type 16, are the primary etiologic agent of
cervical cancer. Thus, HPV-associated cervical
malignancies might be prevented or treated by induction of the appropriate virus-specific immune responses in patients. Sexual transmission of HPV may be prevented by the generation of
neutralizing antibodies that are specific for the virus capsid. In ongoing clinical trials, HPV virus-like particles (VLPs) show great promise as prophylactic
HPV vaccines. Since the
capsid proteins are not expressed at detectable levels by basal keratinocytes, therapeutic
vaccines generally target other nonstructural
viral antigens. Two HPV oncogenic
proteins, E6 and E7, are important in the induction and maintenance of cellular transformation and are coexpressed in the majority of HPV-containing
carcinomas. Therefore, therapeutic
vaccines targeting these
proteins may provide an opportunity to control HPV-associated
malignancies. Various candidate therapeutic
HPV vaccines are currently being tested whereby E6 and/or E7 are administered in live vectors, in
peptides or
protein, in
nucleic acid form, as components of chimeric VLPs, or in cell-based
vaccines. Encouraging results from experimental vaccination systems in animal models have led to several prophylactic and therapeutic
vaccine clinical trials. Should they fulfill their promise, these
vaccines may prevent
HPV infection or control its potentially life-threatening consequences in humans.