Project Title/Research Areas: High Resolution Imaging & HPV Oncoprotein Detection for Global Prevention of Cervical Cancer
Principal Investigator/Institution: Rebecca Richards-Kortum, Ph.D., Rice University, Houston, Texas, USA
Description of Current Activity
Cervical cancer continues to be the 1st or 2nd leading cause of cancer death among women in low- and middle-income countries. In the United States, low socioeconomic status (SES) is strongly correlated with poor cervical cancer survival. In resource-limited settings in the U.S. and abroad, there is a significant need for new point-of-care diagnostics that enable combined detection and treatment of cervical precancer in a single visit. To date, global attempts to implement “see & treat” protocols based on visual inspection with acetic acid (VIA) or HPV testing have been limited by the extremely low specificity.
We hypothesize that a combination of imaging and biomarker detection can reduce the high false positive rate of current cervical screening tools. We have developed an investigational imaging method, high-resolution microendoscopy (HRME), to identify cervical lesions in situ by measuring quantitative parameters including nuclear area, nuclear eccentricity, and nuclear/cytoplasm area ratio. In Aim 1, we have successfully adapted the HRME to a mobile platform that will capture, display, analyze, and transmit images. For Aim 2, we are in the process of evaluating the performance of the mHRME in two globally relevant contexts: in a clinical evaluation of women in the U.S. where we have enrolled 43 patients in Houston, TX and in a clinical evaluation of 3,000 women in El Salvador where we have enrolled 1,057 patients. In these studies, we will assess mHRME imaging in comparison to VIA, colposcopy, and HPV DNA testing. For Aim 3, the overexpression of HPV E7 oncoprotein is one of the best known molecular biomarkers of cervical precancer. Therefore, we are working to develop a rapid, low-cost, lateral flow test to detect E7. Additionally, we have developed a low-cost, paper-based HPV DNA test and are currently evaluating its usability among health care providers in low-resource areas. We will assess the performance of both the HPV E7 oncoprotein test and the HPV DNA test using cervical specimens in a nested case-control of 224 patients with and without cervical precancer who participated in Aim 2.
This work will provide clinicians in the U.S. and globally with robust, affordable, integrated, point-of-care tools to directly image phenotypic changes and detect molecular markers associated with the development and progression of cervical precancer, addressing the poor specificity of current methods. Together, these tools will improve the efficacy and cost-effectiveness of early detection of cervical precancer, allowing diagnosis and treatment in a single visit to prevent the development of invasive cervical cancer.