Cervical cancer precursors and hormonal contraceptive use in HIV-positive women: application of a causal model and semi-parametric estimation methods.


OBJECTIVE: To demonstrate the application of causal inference methods to observational data in the obstetrics and gynecology field, particularly causal modeling and semi-parametric estimation. BACKGROUND: Human immunodeficiency virus (HIV)-positive women are at increased risk for cervical cancer and its treatable precursors. Determining whether potential risk factors such as hormonal contraception are true causes is critical for informing public health strategies as longevity increases among HIV-positive women in developing countries. METHODS: We developed a causal model of the factors related to combined oral contraceptive (COC) use and cervical intraepithelial neoplasia 2 or greater (CIN2+) and modified the model to fit the observed data, drawn from women in a cervical cancer screening program at HIV clinics in Kenya. Assumptions required for substantiation of a causal relationship were assessed. We estimated the population-level association using semi-parametric methods: g-computation, inverse probability of treatment weighting, and targeted maximum likelihood estimation. RESULTS: We identified 2 plausible causal paths from COC use to CIN2+: via HPV infection and via increased disease progression. Study data enabled estimation of the latter only with strong assumptions of no unmeasured confounding. Of 2,519 women under 50 screened per protocol, 219 (8.7%) were diagnosed with CIN2+. Marginal modeling suggested a 2.9% (95% confidence interval 0.1%, 6.9%) increase in prevalence of CIN2+ if all women under 50 were exposed to COC; the significance of this association was sensitive to method of estimation and exposure misclassification. CONCLUSION: Use of causal modeling enabled clear representation of the causal relationship of interest and the assumptions required to estimate that relationship from the observed data. Semi-parametric estimation methods provided flexibility and reduced reliance on correct model form. Although selected results suggest an increased prevalence of CIN2+ associated with COC, evidence is insufficient to conclude causality. Priority areas for future studies to better satisfy causal criteria are identified.





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Publication Info

Leslie, Hannah H, Deborah A Karasek, Laura F Harris, Emily Chang, Naila Abdulrahim, May Maloba and Megan J Huchko (2014). Cervical cancer precursors and hormonal contraceptive use in HIV-positive women: application of a causal model and semi-parametric estimation methods. PLoS One, 9(6). p. e101090. 10.1371/journal.pone.0101090 Retrieved from https://hdl.handle.net/10161/12717.

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Megan Justine Huchko

Hollier Family Associate Professor of Global Health

Megan Huchko, MD, MPH, holds a dual appointment as an Associate Professor in the Department of Obstetrics & Gynecology and the Duke Global Health Institute.  Dr. Huchko was an undergraduate at Duke before moving to New York City to complete medical school at the Albert Einstein College of Medicine, and residency training at Columbia Presbyterian Medical Center.  She completed her fellowship in Reproductive Infectious Disease the University of California, San Francisco, and was a faculty member there. 

Dr. Huchko practices as an ob/gyn generalist and specializes in cervical cancer prevention through her clinical work and global women’s health research.  Her research focuses on optimizing the diagnosis and treatment of cervical cancer among vulnerable women in settings where health disparities occur. She has been working with the Family AIDS Care and Education Services (FACES) program in the Nyanza Province of western Kenya since 2006.  

She designed and implemented a cervical cancer screening and prevention (CCSP) program for HIV-infected women enrolled in care at FACES.  The CCSP program has provided a clinical resource, as well as a cohort to evaluate the epidemiology of cervical cancer among HIV-infected women, the feasibility of integrating cervical cancer prevention programs into HIV and general outpatient clinics, the safety of various diagnostic and treatment modalities, the efficacy of low-cost/low-resource screening modalities in HIV-infected women and provider and patient-level barriers and facilitators to uptake of cervical cancer prevention activities.  

Currently, she is carrying out several large studies in central Uganda and western Kenya to evaluate the optimal implementation strategy for HPV-based cervical cancer screening in rural settings.  At Duke, she leads the Center of Excellence in Global Women’s Health through the Global Health Institute and serves as Director for the Ob/Gyn Clinical Research Unit (CRU).

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