Prognostic factors and new therapeutic approaches to cervical cancer

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 p16INK4a 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.