Project Summary Dr. Clark is an Assistant Professor of Pediatric Tropical Medicine and Infectious Diseases at Baylor College of Medicine (BCM) and a physician-scientist trained in immunoparasitology. Her career goal is to become an independent molecular epidemiologist and perform high-quality clinical research that improves the health of people living in low resource settings. The leading cause of cancer death for women in tropical low- and middle-income countries (LMICs) is cervical cancer, which is caused by persistent infection with the human papilloma virus (HPV). Cervical cancer rates are particularly high in LMICs with large intestinal helminth burdens, and preliminary data show a significant population level association between intestinal helminth infection and HPV infection. Dr. Clark proposes to evaluate whether intestinal helminth infection facilitates HPV co-infection by altering the cervico-vaginal environment. She will conduct a cross-sectional study of adult women undergoing cervical cancer screening in Peru. This innovative study aims to determine the prevalence of HPV infection, evaluate cervico-vaginal cytokine profiles, and examine the distribution of cervico-vaginal microbiota in women with and without intestinal helminth infection. Results of this work will suggest novel interventions that are urgently needed to prevent cervical cancer in women living in LMICs. Dr. Clark’s unique skill set will allow her to serve as a link between clinical discovery and public health system implementation of new strategies for cervical cancer prevention. From a public health perspective, if intestinal helminth infection increases a woman’s risk for HPV infection and therefore cervical cancer, deworming—a widely available, low- cost intervention—should reduce the cervical cancer rates, thereby increasing the feasibility of cervical cancer screening program implementation and reducing costs associated with early cervical dysplasia detection and treatment programs. To accomplish these goals, Dr. Clark has developed a comprehensive career development plan that combines thorough mentoring and training activities integrated into her clinical research program. She will have regular meetings with her mentorship team, Dr. Elizabeth Chiao, an authority in virus mediated malignancies and HPV screening, and Dr. Peter Hotez, a leader in parasitology and global health, and will receive additional expert-level mentorship from her scientific advisory committee. Mentored research will be supplemented with formal training activities including graduate-level coursework, directed studies, ad participation in scientific meetings. Her career development plan is supported by a world-class scientific environment at BCM, which offers ample opportunities for junior faculty development and provides all the resources needed to achieve her career goals. The proposed mentored career development activities will provide the focused mentorship and career development activities that Dr. Clark requires to succeed as an independently funded molecular epidemiologist conducting high quality, high impact international research.

Project Narrative Cervical cancer continues to cause disability and death in millions of women living in tropical regions of the world who do not have access to cervical cancer screening and human papilloma virus (HPV) vaccination. People living in tropical countries are commonly infected with intestinal worms (helminths), which can live largely undetected in their hosts by muting the immune response. Understanding the impact of helminth infection on the cervico-vaginal microenvironment may lead to the development of improved cervical cancer prevention strategies in tropical countries.