A low-cost platform for cervical cancer detection
Grant, Benjamin David
Richards-Kortum, Rebecca R
Doctor of Philosophy
Cervical cancer causes an estimated 265,000 deaths annually, 90% of which occur in developing countries. To reduce the global burden of cervical cancer, screening programs and HPV vaccination are needed worldwide. Screening techniques that have had significant success in high resource settings have failed in low-to middle-income countries due to a variety of factors, including lack of highly trained personnel and lack of laboratory infrastructure. Two alternative methods have been employed for cervical cancer screening in low resource settings: visual inspection with acetic acid and human papillomavirus (HPV) DNA testing. While both methods are promising, they both suffer from low specificity. In this thesis, I explored the ability of the high-resolution microendoscope (HRME) to discriminate between neoplastic cervical precancerous lesions and benign conditions in vivo in a pilot study of 59 patients in Barretos, Brazil. By calculating mean nuclear eccentricity and area, neoplastic lesions were discriminated from benign conditions with 92% and specificity of 77%. Further, I designed a new mobile-phone based HRME which reduced the size of the HRME by a factor of four and the prototype cost from $5,000 to $1,700. In addition to imaging techniques, I explored low-cost immunoassays to aid both in cervical cancer screening and HPV vaccination efforts. Detection of the HPV oncoprotein E7 in cervical swabs may offer more specificity than HPV DNA testing, but current testing is both time and equipment intensive. I have developed a paper-based platform for running highly sensitive immunoassays without the need for sophisticated laboratory equipment. In a proof-of-principle malaria antigen assay, this device achieved equivalent limit-of-detection to a standard ELISA. Additionally, I present a modified version of this device for a serological HPV antibody test. In a pilot study of 24 volunteers, the test correctly identified those who had received two or more HPV vaccines with 100% accuracy. Such a test is needed to reduce unnecessary revaccination and to promote efficient vaccination in settings with poor medical records. This work provides an improvement upon the HRME imaging technique and a highly sensitive point-of-care molecular diagnostic platform to aid in cervical cancer screening, detection and prevention in low-resource settings. The preliminary results from clinical pilot studies provide the foundation for further work to help reduce the global cervical cancer burden.
cervical cancer; point-of-care, high-resolution microendoscopy