High resolution imaging & HPV oncoprotein detection for global prevention of cerv

高分辨率成像

• 批准号: 8912437
• 负责人: Rebecca R. Richards-Kortum
• 金额: $ 60.3万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8912437
• 关键词: Acetic Acids; Address; Adenocarcinoma; Bedside Testings; Biological Assay; Biological Markers; Biopsy; Botswana; Cancer Etiology; Cells; Cellular Phone; Cervical; Cervix Uteri; Cessation of life; China; Cold Therapy; Colposcopy; Country; Cytology; Cytology Histology; DNA; Detection; Developing Countries; Development; Diagnosis; Diagnostic; Disease; Distal; Early Diagnosis; Early treatment; El Salvador; Endoscopes; Epithelial; HPV-High Risk; Health; Healthcare; Human Papillomavirus; Human Resources; Human immunodeficiency virus test; Image; Image Analysis; In Situ; In Situ Lesion; Income; Lateral; Lesion; Loop electrosurgical excision procedure; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Methods; Molecular; Morbidity - disease rate; Nuclear; Oncogene Proteins; Outpatients; Pap smear; Patients; Performance; Pilot Projects; Premalignant; Prevention; Process; Protocols documentation; Research Infrastructure; Resolution; Resources; Risk; Rural; Side; Socioeconomic Status; Specificity; Specimen; Staging; Swab; Techniques; Technology; Test Result; Testing; Time; Tissues; Training; Unnecessary Procedures; Visit; Visual; Woman; Work; base; cancer diagnosis; case control; cost; cost effectiveness; follow-up; global health; high risk; imaging biomarker; imaging modality; improved; in vivo; low socioeconomic status; meetings; molecular marker; mortality; novel; novel strategies; overexpression; performance tests; point of care; point-of-care diagnostics; prevent; research clinical testing; screening; tool; usability; wasting

DESCRIPTION (provided by applicant): Cervical cancer continues to be the 1st or 2nd leading cause of cancer death among women in low- and middle- income countries. In the U.S., 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 have been limited by the extremely low specificity of the three existing diagnostic approaches that can be used at the point-of-care. "See & treat" protocols based on imaging (colposcopy or visual inspection with acetic acid (VIA)) or biomarker detection (HPV DNA testing) result in high rates of overtreatment, subjecting patients to unnecessary procedures and wasting healthcare resources. We hypothesize that a combination of imaging and biomarker detection can reduce the high false positive rate of current cervical screening tools. Increased nuclear-to-cytoplasmic (N/C) ratio is one of the best known phenotypic biomarkers of cervical precancer, but can currently only be assessed from cytology or biopsy. We have developed an investigational imaging method, high-resolution microendoscopy (HRME), to identify cervical lesions in situ with increased N/C ratio. In Aim 1, we will adapt the HRME to a mobile platform which incorporates a cell phone to capture, display, analyze, and transmit images. We will then evaluate the performance of the mobile HRME (mHRME) with an existing biomarker (HPV DNA testing) and an investigational biomarker (HPV E7 oncoprotein). In Aim 2, we will evaluate performance of the mHRME in two globally relevant contexts: (A) in a clinical evaluation of 429 women in the U.S., we will assess whether addition of mHRME imaging improves specificity of colposcopy, without significantly reducing sensitivity; (B) in a clinical evaluation of 4,592 women in El Salvador, we will assess whether mHRME imaging improves the specificity of screening by VIA alone, HPV DNA testing alone, or with HPV DNA testing followed by VIA. Overexpression of HPV E7 oncoprotein is one of the best known molecular biomarkers of cervical precancer. To further improve specificity of molecular testing, in Aim 3 we will develop a rapid, low-cost, laterl flow test to detect E7. We will assess test performance using cervical specimens in a nested case-control of 270 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.

描述（由申请人提供）：子宫颈癌仍然是低收入和中等收入国家妇女癌症死亡的第一或第二大原因。在美国，低社会经济地位（SES）与宫颈癌生存率低密切相关。在美国和国外资源有限的环境中，对新的护理点有很大的需求