Recent advances in the detection and
therapy of
carcinoma of the cervix and its squamous intra-epithelial precursor lesions exploit the knowledge that these lesions are a consequence of
infection with high risk (HR) human papillomavirus (HPV).
HPV infections over-ride cell cycle controls and antibody based immunodetection of
proteins that regulate DNA replication may facilitate mass automated cervical smear screening. Detection of HR HPV
DNA in smears from selected patient groups will improve detection of high grade precursor lesions and immunodetection of the cell cycle dependent
kinase inhibitor
p16(INK4a) seems to specifically and sensitively identify HGSIL. Immunisation with HPV early
proteins has been shown to have both prophylactic and therapeutic efficacy in animal
papillomavirus infections and
immunotherapies for low grade intra-epithelial lesions are realistic. Such
vaccines are likely to be combined with
immunomodulators in order to maximise the response.
Immunotherapies for HPV associated high grade pre-
cancers and invasive
cancers are problematic in view of tumour immune evasion. However, anti-viral
chemotherapies may benefit from the neoplastic phenotypic by the induction of: (1) apoptosis as a consequence of small molecule or anti-sense targeting of individual HPV
oncoproteins and (2) replicative senescence by down regulation of the early promoter by E2 or small molecule homologues.