Precision methylation biomarkers linked to cancer disparities

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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.