"High-risk" genotypes of the human papillomavirus (HPV), most commonly HPV genotype 16, are the primary etiologic agents of
cervical cancer. Indeed HPV
DNA is detected in 99% of cervical
carcinomas. Thus,
cervical cancer and other HPV-associated
malignancies might be prevented or treated by the induction of the appropriate
viral-antigen-specific immune responses. Transmission of papillomavirus may be prevented by the generation of
antibodies to
capsid proteins L1 and L2 that neutralize
viral infection. HPV L1 virus-like particles (VLPs) show great promise as prophylactic
HPV vaccines in ongoing clinical trials but L2-based preventative
vaccines have yet to be tested in patients. Since the
capsid proteins are not expressed at detectable levels by infected basal keratinocytes or in HPV-transformed cells, therapeutic
vaccines generally target the nonstructural early
viral antigens. Two HPV oncogenic
proteins, E6 and E7, are critical to the induction and maintenance of cellular transformation and are co-expressed in the majority of HPV-containing
carcinomas. Although other early
viral antigens show promise for vaccination against
papillomas, therapeutic
vaccines targeting E6 and E7 may provide the best 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, as
peptides or
proteins, 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 this new generation of HPV preventative and therapeutic
vaccines function in patients as demonstrated in animal models, oncogenic
HPV infection and its associated
malignancies could be controlled by vaccination. Importantly, recent advances in HPV detection and continued improvements in screening further enhance our opportunities to systematically eradicate HPV-associated
malignancy.