Preventive and therapeutic vaccines for human papillomavirus-associated cervical cancers

'High risk' genotypes of the human papillomavirus (HPV), particularly HPV t ype 16, are the primary etiologic agent of cervical cancer. Thus, HPV-assoc iated cervical malignancies might be prevented or treated by induction of t he appropriate vii us-specific immune responses in patients. Sexual transmi ssion of HPV may be prevented by the generation of neutralizing antibodies that are specific for the virus capsid. In ongoing clinical trials, HPV vir us-like particles (VLPs) show great promise as prophylactic HPV vaccines. S ince the capsid proteins are not expressed at detectable levels by basal ke ratinocytes, therapeutic vaccines general ly target other nonstructural vir al antigens, Two HPV oncogenic proteins, E6 and E7, are important in the in duction and maintenance of cellular transformation and are coexpressed in t he majority of HPV-containing carcinomas. Therefore, therapeutic vaccines t argeting these proteins may provide an opportunity to control HPV-associate d malignancies. Various candidate therapeutic HPV vaccines are currently be ing tested whereby E6 and/or E7 are administered in live vectors, in peptid es or protein, in nucleic acid form, as components of chimeric VLPs, or in cell-based vaccines. Encouraging results from experimental vaccination syst ems in animal models have led to several prophylactic and therapeutic vacci ne clinical trials. Should they fulfill their promise, these vaccines may p revent HPV infection or control its potentially life-threatening consequenc es in humans.