Cervical cancer rate has steadily decreased over the past fifty years due to broadly available screening and follow-up programs that detect and treat abnormal cervical lesions, respectively, but still remains a considerable burden worldwide with nearly 300,000 deaths each year. The main reason in the development of cervical cancer is the infection of cervical cells with high-risk human papilloma viruses. Although most women will come in contact and get infected with HPV at some point during their lifetime, only women with persistent HPV infection are truly at risk of developing cervical cancer. Molecular testing for high risk HPV DNA may detect infection too early in the process.

      However, since a small subset of women will develop the disease that progresses to cancer, it is necessary to define secondary biomarkers that have potential application in identification of women who need to be followed more closely because they are at higher risk of developing high-grade lesions. For this purpose, in this proposal we will test and validate several candidate biomarkers by performing gene expression and mutation analysis on RNA and DNA samples respectively isolated from exfoliated cervical cells. There are several known changes in the expression of proliferation/cell cycle and apoptotic biomarkers, the amplification and methylation status of certain genes, as well as in the mutation status of key oncogenes associated with cancer progression and precancerous and cancerous stages. The main aim of our study is the development of an accurate molecular signature of biomarkers that would constitute a cheaper, non-invasive and more accurate tool for identification of high-risk HPV positive women. The outcome of the proposed study is anticipated to have high prognostic value and will help towards a tailored management based on the patients’ risk profiles.