A Randomized Controlled Trial for Treatment of High-Grade Cervical Lesions Among HIV-Infected Women in Kenya

Sharon Greene | 2018

Advisor: Grace C. John-Stewart

Advisor: Rachel L. Winer

Research Area(s): Cancer Epidemiology, Global Health, Infectious Diseases, Maternal & Child Health


HIV and cervical cancer are co-epidemics that disproportionally impact women living in low resource settings. Women infected with HIV have consistently been reported to have higher burden of human papillomavirus (HPV) infection, persistent HPV infection, and cervical pre-cancerous lesions than HIV-uninfected women. These lesions, if left untreated, can progress to cervical cancer. For women with high grade cervical pre-cancer, current World Health Organization (WHO) guidelines recommend treatment with either cryotherapy or loop electrosurgical excision procedure (LEEP). A key challenge is the specificity of these guidelines to address the complex needs of women infected with human immunodeficiency virus (HIV). Published evidence suggests that cervical pre-cancer has a different disease course among HIV-infected women than women in the general population. Previous studies have shown that treatment with cryotherapy or LEEP in HIV-infected women may stimulate cervical shedding of HIV and subsequently increase the risk of HIV sexual transmission from treated women to HIV-uninfected partners. Cryotherapy and LEEP have both been associated with cervical shedding of HIV, but they have never been directly compared to each other and few studies have rigorously studied treatment outcomes among HIV-infected women. Our findings support the current guidelines that HIV-infected women should either avoid sexual intercourse for one month or practice risk reduction strategies including condom use to minimize risk of HIV-infection. High grade cervical pre-cancer can be difficult to treat and recurs in approximately 5-14% of women after treatment and among HIV-infected women, recurrence has been reported as high as 23%. There have been conflicting results and conclusions from observational studies and randomized trials that assessed effectiveness of cryotherapy or LEEP. The consistency and quality of evidence varies because the data are pooled from observational studies that define different end points, post-treatment follow-up times are too short to accurately measure the impact of treatment on recurrence, or the sample sizes have not been large enough to precisely measure how recurrence is modified HIV-cofactors. We addressed these limitations by using a robust study design, gold-standard outcome definition, and a long duration of follow-up. We found that, cryotherapy was associated with significantly higher risk of recurrent pre-cancerous cervical disease, suggesting that LEEP should be adopted as the standard of care for HIV-infected women. This research has contributed to an improved understanding of how treatment for high grade cervical lesions in HIV-infected women affects short-term risk of HIV transmission and the long-term risk of recurrence of cervical disease. For secondary prevention of cervical cancer to be programmatically effective, HIV-status must be addressed by treatment guidelines for high grade cervical pre-cancer.