Project Summary/AbstractsCervical cancer remains a significant health problem in low- and middle- income countries (LMICs). More than80% of the 530000 annual cervical cancer cases and 270000 annual cervical cancer-related deaths occur inLMICs. Lack of resources for conducting organized screening and treatment services in LMICs leads to latestage diagnosis of cervical malignancy. As a result of this resource shortage cervical cancer associatedmortality rate in east African countries is 27.6 per 100000 which is unacceptably high when compared to 2.3per 100000 in the US. Visual inspection with acetic acid (VIA) and HPV tests are the two low-cost screeningapproaches commonly utilized in LMICs. Several studies showed that cervical cancer incidence rate can bereduced by screening with HPV and VIA tests and treating the patient accordingly. However main drawback ofthe VIA and HPV tests is low specificity as most women with a positive screening result (80% to 90%) will nothave significant cervical malignancy that warrants treatment (i.e. cervical precancer or cancer). The resultingovertreatment exposes low-risk women to unnecessary morbidity and poses a strain on resources. Confocalmicroscopy provides both high sensitivity (93-100%) and specificity (93-100%) in detecting cervical precancerbut its utility in LMICs has been limited due to the high device cost (>$50000). We are proposing a newapproach of accurately diagnosing cervical precancer with a low-cost (<$3000) smartphone confocalendoscope and providing adequate treatment in a single visit. In this approach suspected cervical lesions areimaged in vivo with the smartphone confocal endoscope. Cellular morphologies visualized in confocal imagesare quantitatively analyzed to diagnose cervical precancer and adequate treatment is performed during thesame visit. Our approach will improve patient care in two areas: i) with high specificity of confocal microscopywe will be able to reduce unnecessary overtreatment; and ii) with the low device cost we will enhance a single-visit screen-and-treat method in rural clinics. In this R21 project we will develop the smartphone confocalendoscope and conduct a pilot study of imaging cervix in vivo in Uganda. We have previously developed a low-cost smartphone confocal microscope and have demonstrated in vivo confocal skin imaging in Uganda. In thisproject we are translating the smartphone confocal microscopy technology for cervical imaging by developinga miniature endoscopic catheter. In Aim 1 we will develop a smartphone confocal endoscope for imagingcervix. We will optimally design i) a low-cost smartphone confocal module that connects with ii) a miniatureendoscopic catheter and test the imaging performance. In Aim 2 we will demonstrate in vivo confocal imagingof cervix in patients in Uganda. Confocal images will be analyzed in comparison with corresponding histologicimages and preliminary analysis will be conducted on diagnostic accuracy. We strongly believe that our low-cost smartphone confocal microscopy technology will greatly improve the early diagnosis of a range ofconditions with the ultimate goal of helping to reduce health disparity around the globe.