Emily MacDuffie

Outcomes of Loop Electrosurgical Excision Procedures Performed for Severe Cervical Dysplasia in Botswana

PURPOSE In Botswana, a see-and-treat approach to cervical cancer screening is taken. Our objective was to determine the number of loop electrosurgical excision procedures (LEEPs) performed for cervical intraepithelial neoplasia (CIN) 2/3 in Botswana, and follow-up rates and outcomes, among women with positive cervical margins. METHODS Data (patient age, HIV status, margin status, follow-up, and recurrence) from women who underwent LEEP with histologically confirmed CIN 2/3 between January 2014 and December 2015 were analyzed retrospectively. Histopathologic reports were reviewed at a central laboratory in Gaborone, Botswana. Follow-up and recurrence rates were summarized descriptively and compared according to HIV and margin statuses using chi-squared tests. RESULTS In total, 779 women (median age, 39.2 years) underwent LEEP showing CIN2/3; 638 (81.9%) women had CIN3 and 390 (50.1%) had positive LEEP margins (ectocervical, 186 [47.7%]; endocervical [including with ectocervical], 204 [52.4%]). Margin positivity was not associated with HIV status. Of women with positive endocervical margins followed at ≤1 and >1 year, 9.6% and 48.3%, respectively, had persistent CIN2/3 on repeat LEEP. Forty percent (90 of 204) of women with positive endocervical margins had no re-excision documented. CONCLUSION Most women who underwent LEEP had CIN3 and positive margins. Almost half with positive margins followed at >1 year after initial LEEP had CIN2/3 recurrence warranting further treatment; two thirds were not followed. Resources are needed to improve post-LEEP follow-up for women with margin positivity who require additional ablative/excisional procedures to reduce the cervical cancer burden in Botswana.

Patients with Cervical Cancer with and without HIV Infection Have Unique T-cell Activation Profiles despite Similar Survival Outcomes after Chemoradiation

Abstract The global burden of cervical cancer is highest in low- and middle-income countries. Women living with human immunodeficiency virus (HIV) infection are particularly affected by cervical cancer despite availability and adherence to antiretroviral therapy. Immune profile correlates of survival and treatment response have not been widely explored in patients with and without HIV infection. This study recruited women with cervical cancer undergoing definitive chemoradiation (CRT) in Botswana. Clinical characteristics and blood samples were collected. Flow cytometry was performed on samples prior to initiation, at completion, and 3 months after CRT. Logistic regression analysis identified immune markers that differed by HIV status and correlated with overall survival (OS). The study enrolled 131 consecutive women (HIV+ N = 89 and HIV− N = 42). From initiation to 3 months after CRT, a significant decrease in CD4 frequency (72%–60.55%, P < 0.001) and an increase in CD8 frequency (20.9%–31.5%, P < 0.001) were seen in women without HIV, whereas no significant changes in CD4 frequency (52.5%–50.9%) or CD8 frequency (39.9%–41.4%) were observed in those with HIV. Peripheral T cells underwent similar activation across the cohort regardless of HIV status. Improved OS was associated with reduced frequency of IL-2–expressing CD4 T-cell subsets. In women living with HIV, enhanced OS was associated with the presence of proinflammatory CD8 T cells. CRT induces peripheral T-cell activation and distinct cytokine profiles that differ by HIV status. Despite similar OS, HIV infection may differentially affect immune response to CRT in women with well-managed HIV. Significance: Chemoradiation affects the immune system of patients with cervical cancer with well-controlled HIV infection differently than those without HIV, yet their survival does not differ. This finding is an important step in understanding how management of HIV infection can modify cancer outcomes, particularly in settings with a high burden of HIV.

Benchmarking of the Cervical Cancer Care Cascade and Survival Outcomes After Radiation Treatment in a Low- and Middle-Income Country Setting

Delays in care for patients with cervical cancer in Botswana can be benchmarked using a multidisciplinary clinic model.