High-risk human papillomavirus (HPV-16, 18 & others) have been implicated in the etiology of greater than 90% of anogenital premalignant and malignant disease. The viral oncoproteins E6 and E7 both continue to be expressed in tumours contributing to the disease process by a variety of interactions with cellular proteins. E6 in particular is thought to inhibit the normal cellular apoptotic response that should result from virus infection. There is experimental evidence that shows blocking the expression or function of E6 can induce the apoptosis of cultured HPV-16 positive cervical carcinoma cells. Our intention was to identify an inhibitory peptide that neutralises the oncogenic effect of the HPV-16 E6 oncoprotein. The strategy was to generate open reading frame fragments from the full length E6 oncogene by PCR, and use these to produce peptide fragments. The peptide fragments were assessed for their ability to block the parental HPV-16 E6 protein binding to its ligands in HPV positive and negative cell lines. The results from these in vitro experiments show that it is possible to achieve specific intracellular targeting of the HPV-16 E6 oncoprotein. The R11/10 peptide was shown to be able to induce death in HPV-16 positive cancer cells and cause growth inhibition, whereas the effects in HPV-negative cells were minimal. An effective treatment of cervical disease is dependent not only on an efficient therapeutic strategy which specifically targets HPV infected cervical cancer cells, but also the availability of novel biomarkers that enables detection of pre-malignant lesions. Current diagnosis uses Papanicoleau smear tests, which have significantly improved the detection of pre-malignant cervical intraepithelial neoplasia (CIN). However, it is not capable of differentiating between those patients who spontaneously regress and those who go on to develop the cancer. It was our intention to identify predictive patterns of gene expression, which could be used to diagnose progressive cervical intraepithelial (CIN) lesions. Human cancer 1.2 cDNA arrays (Clontech) were used to analyse differences in gene expression between normal, pre-malignant and malignant cervical tissues. This is a pilot study and so far we have screened 12 cervical carcinomas, 4 CIN, and 4 normal biopsies. One hundred and ninety-eight genes were identified, whose expression was either down- or up-regulated in diseased tissue when compared to biopsies from normal cervix. From a panel of 19 genes that were up-regulated, 2 genes LRP and IP-10 were selected for further investigation. The array results were validated on paraffin sections and ThinPrep cervical smear slides using an immunohistochemistry method. The expression of LRP gene was well correlated between the transcript and protein levels, and the LRP staining of cervical carcinoma and pre-malignant tissue is indicative that it may have potential use as a biomarker for progression of cervical disease.