Precision methylation biomarkers linked to cancer disparities

项目摘要 没有女性应该死于宫颈癌，然而宫颈癌是世界上第三大女性恶性肿瘤，仅次于 乳腺癌和结直肠癌。宫颈癌也是差异最明显的肿瘤之一。 全世界。几十年来，在美国的拉丁裔中，宫颈癌的发病率和死亡率一直较高。 然而，最近发表的一项研究显示，根据子宫切除手术的数量进行调整后，美国白人和黑人女性的宫颈癌死亡率比之前认为的要高得多。黑人女性死于宫颈癌的比率比之前认为的高出77%，白人女性的死亡率高出47%。在将接受子宫切除术的女性从死亡率计算中剔除后，不同种族宫颈癌死亡率的差异翻了一番，从每10万名妇女中有2.7人增加到5.4人。据推测，拉美裔女性的情况也是如此，但目前还没有数据来证实情况是否如此。 使用细胞学筛查(巴氏涂片)和致癌性人乳头瘤病毒(HPV+)基因分型是有效的 确定哪些女性可能有患宫颈癌的风险，但不能用来预测谁更有可能患上宫颈癌 癌症。在美国，对于持续HPV+感染和巴氏杆菌异常的女性，目前的实践标准是 阴道镜检查和随后的活检。然而，这些活组织检查中的大多数(55%-70%)是在没有临床疾病的妇女身上进行的 该项目的目标是证明CervicalMethDx检测的商业化可行性，这是一种精密的检测方法。 宫颈癌筛查领域的甲基化。我们将重点关注持续致癌性人乳头瘤病毒(HPV+)感染的患者，他们被转诊到阴道镜检查和随后的活检，即使大多数患者的活检都是正常的。 我们正在与David Sidransky的研究实验室合作，以优化CervicalMethDx测试，并与约翰霍普金斯大学西德尼·基梅尔癌症中心的教育和外展部合作，为巴尔的摩低收入社区的居民引入精确的表观遗传学服务。对HPV阳性女性进行阴道镜检查的有效分流将减少不必要的活检，提高医疗质量，降低医疗成本，并减少美国现有的宫颈癌死亡率差距。

Project Summary No woman should die of cervical cancer, yet cervical cancer is the third leading malignancy among women in the world, after breast cancer and colorectal cancer. Cervical cancer is also one of the tumors in which the most glaring disparities exist worldwide. Cervical cancer incidence and mortality has been higher for decades among Latinas in the United States (US). However, a recently published study revealed that cervical cancer death rates among White and Black women in the US are much higher than previously thought, after adjusting for the number of hysterectomies performed. Black women are dying from cervical cancer at a rate 77% higher than previously thought, and white women are dying at a rate 47% higher. The disparity in cervical cancer mortality rates by race doubled, from 2.7 to 5.4 per 100,000 women, after removing women with hysterectomies from mortality calculations. Presumably, the same is the case for Latina women, but there is currently no data available to verify if this is the case. The use of cytology screening (Pap smear) and oncogenic Human papilloma Virus (HPV+) genotyping are effective in identifying women who may be at risk for cervical cancer, but cannot be used to predict who is more likely to develop cervical carcinoma. Current standard of practice in the US for women with persistent HPV+ infection and abnormal Pap is referral to colposcopy and subsequent biopsy. However, most of these biopsies (55%-70%) are performed in women without clinical disease The goal of this project is to demonstrate the feasibility for the commercialization of the CervicalMethDx Test, a precision methylation for the cervical cancer screening space. We will focus on patients with persistent oncogenic Human Papilloma Virus (HPV+) infection, who are referred into colposcopy and subsequent biopsy, even when most will have a normal biopsy. We are partnering with David Sidransky's research laboratory to optimize the CervicalMethDx Test and with the Education and Outreach Department of the Johns Hopkins Sidney Kimmel Cancer Center to introduce precision epigenetic services to residents of low-income neighborhoods in Baltimore. Efficient triage of HPV+ women into colposcopy will decrease unnecessary biopsies, improve health care quality, decrease health care costs, and reduce existing cervical cancer mortality disparities in the US.