Dr. Megan Clarke conducts research combining molecular, clinical, and population-based approaches to address etiology, prevention, and early detection of anogenital and endometrial cancers, yielding results that inform natural history and clinical management and address cancer disparities. She also has a strong interest in developing methods for absolute risk assessment from clinical databases and assay evaluation.
Human papillomavirus (HPV) DNA testing has greatly improved the reach and sensitivity of cervical cancer screening compared to Pap cytology. However, triage tests are needed to determine who among the many HPV-positive women require treatment, while avoiding unnecessary harm to women at low risk. In her research, Dr. Clarke has identified host gene and HPV DNA methylation as promising biomarkers for cervical carcinogenesis that can outperform current triage tests. She is collaborating with the Cancer Genome Research Laboratory to develop a low-cost, next-generation sequencing methylation assay. Dr. Clarke is leading several efforts to validate this assay in natural history studies and has designed a study (Selfie) for large-scale evaluation of methylation testing in self-collected samples. Results from this study will provide critical groundwork for including HPV methylation as a screening approach in NCI Moonshot-funded efforts to accelerate cervical cancer control worldwide. In addition, she is studying the association of methylation markers with anal precancers and cancers, an area in need of accurate biomarkers.
Dr. Clarke also has a strong interest in studying cervical cancer disparities including race, ethnicity, and other factors such as obesity. With colleagues from the University of Mississippi Medical Center and The Mississippi State Department of Health, she developed a statewide study of women undergoing cervical cancer screening in Mississippi. STRIDES (STudying Risks to Improve DisparitiES in cervical cancer in Mississippi) will enroll more than 30,000 women from a diverse population with over 50 percent Black women to explore novel questions related to disease natural history, cervical cancer risk assessment, and the performance of novel triage markers for cervical cancer screening, which may vary by race.
Dr. Clarke’s research has contributed to the scientific evidence that supports the newly published clinical management guidelines for cervical cancer; Dr. Clarke serves on guidelines committees for cervical cancer and is a working group leader on the International Anal Neoplasia’s Society’s Task Force to develop anal cancer screening guidelines.
Endometrial cancer is an understudied and under-appreciated disease whose research lags behind that of other cancers in terms of natural history and clinical management. In response, Dr. Clarke is building a comprehensive endometrial cancer research portfolio, covering natural history, epidemiology and risk assessment, and biomarker development for early detection. Similar to her work in cervical cancer, she is evaluating self-sampling strategies with vaginal tampons to improve endometrial cancer detection. In a prospective cohort study conducted at the Mayo Clinic, Dr. Clarke will evaluate risk prediction strategies and novel early detection approaches in tampon samples from women with abnormal uterine bleeding.
In analyses of hysterectomy-corrected endometrial cancer incidence rates and survival in the Surveillance and Epidemiology and End Results (SEER) database, Dr. Clarke showed that recent increases in endometrial cancer incidence have been primarily due to rising rates of aggressive, non-endometrioid subtypes which are more common in non-Hispanic black women and less strongly associated with well-established risk factors like obesity. To better understand the etiology and natural history of these aggressive subtypes and differences by race, Dr. Clarke designed the DETECT Study (Discovery and Evaluation of Tests for Endometrial Cancer in Tampons), to assess endometrial cancer risk factors and evaluate the performance of biomarkers measured in tissue and vaginal tampons in women undergoing hysterectomy for endometrial cancer or benign conditions at the University of Alabama.
Dr. Clarke earned an M.H.S. in biochemistry and molecular biology in 2010 and a Ph.D. in epidemiology in 2016, both from the Johns Hopkins Bloomberg School of Public Health. She completed postbaccalaureate and postdoctoral (as a Cancer Prevention fellow) fellowships in the Clinical Genetics Branch. She was promoted to research fellow in 2019 and was appointed as an Earl Stadtman Tenure-Track Investigator in 2020. Dr. Clarke has received numerous awards for her work, including an Intramural Research Award, NCI Director’s Intramural Innovation Award, and the William G. Coleman Jr. Ph.D., Minority Health and Health Disparities Research Innovation Award.
- Clarke MA, Devesa SS, Harvey SV, Wentzensen N. Hysterectomy-Corrected Uterine Corpus Cancer Incidence Trends and Differences in Relative Survival Reveal Racial Disparities and Rising Rates of Nonendometrioid Cancers. J Clin Oncol. 2019;37(22):1895-1908.
- Clarke MA, Fetterman B, Cheung LC, Wentzensen N, Gage JC, Katki HA, Befano B, Demarco M, Schussler J, Kinney WK, Raine-Bennett TR, Lorey TS, Poitras NE, Castle PE, Schiffman M. Epidemiologic Evidence That Excess Body Weight Increases Risk of Cervical Cancer by Decreased Detection of Precancer. J Clin Oncol. 2018;36(12):1184-1191.
- Clarke MA, Long BJ, Del Mar Morillo A, Arbyn M, Bakkum-Gamez JN, Wentzensen N. Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women: A Systematic Review and Meta-analysis. JAMA Intern Med. 2018;178(9):1210-1222.
- Clarke MA, Gradissimo A, Schiffman M, Lam J, Sollecito CC, Fetterman B, Lorey T, Poitras N, Raine-Bennett TR, Castle PE, Wentzensen N, Burk RD. Human Papillomavirus DNA Methylation as a Biomarker for Cervical Precancer: Consistency across 12 Genotypes and Potential Impact on Management of HPV-Positive Women. Clin Cancer Res. 2018;24(9):2194-2202.
- Clarke MA, Long BJ, Sherman ME, Lemens MA, Podratz KC, Hopkins MR, Ahlberg LJ, Mc Guire LJ, Laughlin-Tommaso SK, Bakkum-Gamez JN, Wentzensen N. Risk assessment of endometrial cancer and endometrial intraepithelial neoplasia in women with abnormal bleeding and implications for clinical management algorithms. Am J Obstet Gynecol. 2020;223(4):549.e1-549.e13.
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Genetics and Genomics
This page was last updated on Wednesday, January 19, 2022