This Program Project uses the rigorous paradigm of technology assessment to evaluate optical technologies and molecular imaging for the screening and diagnosis of cervical cancer. We will identify opportunities in which technology could improve outcomes, decrease costs, and replace infrastructure. Optical measurement of tissue provides quantitative information that can be analyzed, instantaneously producing an objective diagnosis even in the hands of a non-expert operator. We will conduct multi-center clinical trials to assess the screening and diagnostic potential of several emerging technologies: a fluorescence/reflectance point probe, a multispectral digital colposcope, confocal micrsoscopy, and new contrast agents to mark cervical lesions that may be used in combination with other devices. This Program Project will also develop and evaluate a system that combines a point probe with multispectral imaging, and we will create low-cost, portable imaging devices that are optimized to meet health care needs in the developing world and underserved areas of the United States. Specifically, we will measure the sensitivity, specificity, cost-effectiveness, degree of patient discomfort, time-to-result, and training requirements associated with new instruments and techniques. We will compare these systems to the standard-of-care and to each other to find optimized solutions for low- and high-resource settings. We maintain a pipeline of innovation that brings devices from the laboratory bench to the bedside. Although new HPV vaccines may eventually have a strong impact on cervical cancer incidence, the biological limitations of current vaccines and the logistical difficulty associated with universal mass vaccination programs mean that early detection will remain our best defense against cervical cancer for the forseeable future.