Megan Clarke Departs DCEG
, by Jennifer Loukissas, M.P.P.
Megan Clarke, Ph.D., M.H.S., former Earl Stadman investigator in the Clinical Genetics Branch, began a new position at the pharmaceutical firm Abbvie in September 2024. During her tenure in DCEG, she combined molecular, clinical, and population-based approaches to address etiology, prevention, and early detection of human papillomavirus (HPV)-associated anogenital and endometrial cancers. Her discoveries advanced understanding of natural history, influenced clinical management guidelines, and addressed cancer disparities.
Advances in cervical cancer screening, with a shift to HPV DNA testing, revealed a need for triage tests to determine who among the many women who test positive require treatment while avoiding unnecessary harm to women at low risk. Dr. Clarke identified host gene and HPV DNA methylation as promising biomarkers for cervical carcinogenesis that can outperform current triage tests. In collaboration with the Cancer Genome Research Laboratory, she developed a low-cost, next-generation sequencing methylation assay and led several validation efforts in natural history studies, including the Selfie Study, a 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 efforts to accelerate cervical cancer control worldwide and clinical practice, funded by NCI Cancer Moonshot.
Dr. Clarke also has a strong interest in studying cervical cancer disparities by race, ethnicity, and other factors such as obesity. With colleagues from the University of Mississippi Medical Center in Jackson 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) enrolled 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.
She applied these same approaches to the prevention of anal precancer. Although anal cancer is rare in the general population, certain groups, including people with HIV, particularly men who have sex with men (MSM), have a much higher risk. Other groups with elevated risk include women with HIV, MSM without HIV, and women with a history of lower genital tract disease.
To evaluate the performance of HPV-related biomarkers for detection of anal precancer among individuals from different risk groups undergoing anal cytology, HPV testing, and high resolution anoscopy, Dr. Clarke launched the Anal Cancer Etiology and Screening (ACES) Study in collaboration with investigators at Icahn School of Medicine at Mount Sinai who run an Anal Cancer Prevention Program. The U.S. Anal Cancer HSIL Outcomes Research (ANCHOR) study demonstrated that treating anal precancers significantly reduces the risk of progression to anal cancer in people with HIV, emphasizing the importance of screening for anal HSIL for anal cancer prevention. The ACES study is meeting this need by evaluating the performance of HPV genotyping, dual stain, and HPV and host methylation biomarkers for detection of anal precancer among patients.
As part of the International Anal Neoplasia Society, Dr. Clarke helped to develop and publish evidence-based recommendations for anal cancer screening in populations with elevated risk.
Dr. Clarke made critical advances in our understanding of the epidemiology of endometrial cancer, an understudied disease whose research lags those of other cancers in terms of natural history and clinical management. In particular, she identified inequities in incidence and outcomes by race and ethnicity, opening opportunities for research to begin to address those differences. Her comprehensive endometrial cancer research portfolio spanned natural history, epidemiology and risk assessment, and biomarker development for early detection. In a prospective cohort study conducted at the Mayo Clinic in Rochester, Minnesota, she evaluated 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 database, she 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 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 in Tuscaloosa.
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 and was promoted to research fellow in 2019. In 2020, she was appointed as an Earl Stadtman Tenure-Track Investigator and was selected for the NIH Distinguished Scholar Program. 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. In 2021, she received the DCEG Outstanding Mentor Award.