Each year in the United States, ~250,000 women are diagnosed with low-grade cervical dysplasia. Due to the potential for adverse outcomes associated with reflex ablative therapy for low-grade dysplasia and the expectation that 2/3rds of these lesions will resolve on their own, most health care providers take a wait-and-see approach to managing low-grade dysplasia. This approach involves frequent repeat screening by cytology and/or colposcopy-directed cervical biopsies and creates a clinical conundrum: women with low-grade dysplasia that is destined to resolve endure unnecessary follow-up visits, medical procedures, anxiety, and healthcare costs, while intervention is delayed for women whose low-grade dysplasia is destined to progress to high-grade dysplasia or cervical cancer. Currently there is no clinical test that can reliably predict the outcome of low-grade dysplasia (natural resolution vs progression). This application investigates the potential of microRNAs (miRNAs) to serve as predictors of the fate of low-grade cervical dysplasia. The hypothesis is that microRNAs can be used clinically to predict progression of low-grade to high-grade dysplasia/cervical cancer. Two specific aims are proposed. First, candidate prognostic miRNAs will be identified by comparing miRNA expression profiles in women whose low-grade dysplasia resolved to the miRNA expression profiles in women whose low-grade dysplasia progressed, using archived clinical biopsy specimens. Second, the feasibility of using Pap smear samples as a surrogate to biopsy for miRNA testing will be ascertained. This research forms the foundation for the development of new screening tests that will inform management of low-grade cervical dysplasia.