Precision methylation biomarkers for cervical cancer prevention in low resource settings in Latin America

拉丁美洲资源匮乏地区预防宫颈癌的精准甲基化生物标志物

基本信息

批准号：
10654910
负责人：
Rafael Guerrero-Preston
金额：
$ 100万
依托单位：
LIFEGENE-BIOMARKS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10654910
关键词：
Ablation Acetic Acids Acids Age Algorithms Area Under Curve Argentina Baltimore Biological Assay Biological Markers Biopsy Blinded Cervical Cervical Cancer Screening Cervical Intraepithelial Neoplasia Cervix carcinoma Cessation of life Chilean Clinic Clinical Colombia Colorectal Cancer Colposcopy Communities Country Cytology DNA DNA Sequence Developed Countries Disease Epigenetic Process Epithelial Evaluation Excision FDA approved Future Genomics Genotype Glare Goals HPV-High Risk Health Health Care Costs Health Promotion High Risk Woman Honduras Human Papillomavirus Human papilloma virus infection Hysterectomy Incidence Intellectual Property Laboratories Laboratory Research Latin America Legal patent Lesion Licensing Liquid substance Malignant Neoplasms Malignant neoplasm of cervix uteri Medical Methylation Modality Oncogenic Pap smear Paraguay Patients Performance Phase Policies Predictive Value Preventive treatment Prospective Studies Protocols documentation Public Health Publishing Puerto Rico Reflex action Resource-limited setting Retrospective Studies Risk Sampling Sensitivity and Specificity Services Site Small Business Innovation Research Grant Specificity Squamous intraepithelial lesion Swab Technology Testing Time Triage United States Universities Urine Vagina Validation Viral Visual Woman World Health Organization base biomarker development black women cervical cancer prevention clinical risk cohort commercialization cost feasibility testing health care quality high risk improved instrument intraepithelial low and middle-income countries low income country malignant breast neoplasm methylation biomarker methylation testing mortality mortality disparity performance tests phase 1 testing prevent programs racial disparity recruit screening standard of care tool treatment guidelines tumor unnecessary treatment

项目摘要

Project Summary No woman should die from cervical cancer. We have the technical, medical and policy tools and approaches to eliminate it. Yet, one woman dies of cervical cancer every two minutes. Cervical cancer is the third leading malignancy among women in the world, after breast and colorectal cancer. Cervical cancer is also one of the tumors in which the most glaring disparities exist worldwide. The dramatic disparity in incidence rates between high- and low-income countries is due primarily to differential access to effective screening and pre- cancer, or preventive, treatment; similar disparities also exist within countries. Recently published hysterectomy-corrected cervical cancer mortality rates in the United States reveal a larger racial disparity in black women, that previously calculated and shows that the oldest black women have the highest cervical cancer mortality rates. Nonetheless, more than 80 percent of cases and 88 percent of deaths occur in Low and Middle Income Countries (LMICs). The World Health Organization (WHO) has developed guidelines for treatment of cervical intraepithelial neoplasia 2-3 and screen-and-treat strategies to prevent cervical cancer. In countries where multiple barriers exist for cytology based cervical cancer screening, a variety of alternative algorithms are being used, which include low-cost oncogenic HPV testing, visual inspection with acetic acid, and self-collected vaginal swabs. HPV testing is an excellent alternative to cytology for cervical cancer screening. However, HPV tests identifies women at risk for cervical cancer, but not those HPV-positive women who are most likely to have, or to develop in the near future, significant disease requiring treatment. Current practice is to triage these women by further testing with cytology and colposcopy-driven biopsies in developed countries and excision or ablation therapy in LMICs. The use of DNA biomarkers can reduce the number of women referred to colposcopy while maintaining adequate sensitivity and specificity. In this Fast Track SBIR project, we propose to demonstrate the feasibility for the commercialization of a precision methylation test, the CervicalMethDx Test, to stratify HPV+ patients for high risk of cervical cancer, as a reflex test to existing standard of care in LMICs. Our test will enable identification of HPV+ women at clinical risk for advancement from low-grade squamous intraepithelial lesions (LSIL) to Cervical Intraepithelial Neoplasia grade 3 (CIN3). In LMICs, where cervical cytology based-screening will not be implemented, optional modalities of our test will be developed in future projects to stratify HPV+ women at high risk of cervical cancer in self-collected vaginal swabs and/or urine samples. We are partnering with David Sidransky's research laboratory to optimize the CervicalMethDx Test and with the ESTAMPA Study (NCT01881659) Consortium to introduce precision epigenetic services to residents of Honduras, Colombia, Argentina and Paraguay. Efficient triage of HPV+ women will decrease unnecessary treatment, improve health care quality, decrease health care costs, and reduce cervical cancer mortality disparities in LMICs.

项目概要任何女性都不应该死于宫颈癌。我们拥有技术、医疗和政策工具和方法消除它。然而，每两分钟就有一名女性死于宫颈癌。宫颈癌位居第三位继乳腺癌和结直肠癌之后，世界上女性的恶性肿瘤。宫颈癌也是其中之一世界范围内存在最明显差异的肿瘤。发病率的巨大差异高收入国家和低收入国家之间的差异主要是由于获得有效筛查和预检的机会存在差异。癌症或预防性治疗；各国内部也存在类似的差异。最近发表美国经子宫切除术校正的宫颈癌死亡率揭示了更大的种族差异黑人女性，之前计算并显示，最年长的黑人女性的颈椎最高癌症死亡率。尽管如此，超过 80% 的病例和 88% 的死亡发生在低水平地区和中等收入国家 (LMIC)。世界卫生组织 (WHO) 制定了指导方针宫颈上皮内瘤变的治疗 2-3 以及预防宫颈癌的筛查和治疗策略。在基于细胞学的宫颈癌筛查存在多重障碍的国家，有多种替代方法正在使用的算法包括低成本致癌 HPV 检测、醋酸目视检查、以及自行采集的阴道拭子。 HPV 检测是宫颈癌细胞学检查的绝佳替代方法筛选。然而，HPV 检测可识别出有患宫颈癌风险的女性，但无法识别出 HPV 阳性的女性最有可能患有或在不久的将来患上需要治疗的重大疾病的妇女。目前的做法是通过细胞学和阴道镜驱动的活检进一步测试来对这些女性进行分类发达国家和中低收入国家的切除或消融治疗。 DNA生物标志物的使用可以减少许多女性在保持足够的敏感性和特异性的同时接受了阴道镜检查。在这快跟踪SBIR项目，我们建议论证精密仪器商业化的可行性甲基化测试，CervicalMethDx 测试，作为一种反射，对 HPV+ 患者进行宫颈癌高风险分层测试中低收入国家现有的护理标准。我们的测试将能够识别存在临床风险的 HPV+ 女性从低度鳞状上皮内病变（LSIL）进展为宫颈上皮内瘤变 3 级（CIN3）。在中低收入国家，将不实施基于宫颈细胞学的筛查，可选我们的测试方式将在未来的项目中开发，以对宫颈癌高风险的 HPV+ 女性进行分层自行收集的阴道拭子和/或尿液样本中存在癌症。我们正在与 David Sidransky 合作研究实验室优化 CervicalMethDx 测试和 ESTAMPA 研究 (NCT01881659) 联盟将为洪都拉斯、哥伦比亚、阿根廷和巴拉圭。对 HPV+ 女性进行有效分流将减少不必要的治疗，提高医疗保健质量，降低医疗保健成本，并缩小中低收入国家的宫颈癌死亡率差异。