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.

Narrative The goal of this project is to demonstrate the feasibility for the commercialization of the CervicalMethDX Test, a precision methylation test to stratify HPV positive women for high risk of cervical cancer. Cervical cancer, a largely preventable disease, is one of the most common cancers found in women living in low- and middle- income countries (LMICs). A highly sensitive and specific test that can distinguish which HPV positive women with cervical lesions will progress to cancer, will transform cervical cancer screening practices world-wide.