Rebecca Luckett

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.

Improved cervical screening using HPV type restriction and cycle threshold limit setting with the AmpFire assay: A prospective screening cohort of women with and without HIV in Botswana

Abstract Objective The aim of this study was to evaluate the performance of HPV type restriction and cycle threshold (Ct)‐limit setting to optimize detection of cervical intraepithelial neoplasia (CIN) with primary HPV testing. Methods Baseline cervical screening at time of entry into a prospective longitudinal cohort of women with and without HIV was conducted from February 2021 to July 2022 in Botswana. All women underwent HPV testing of 15 individual types using the AmpFire assay; all HPV‐positive and a random subset of HPV negative had histopathology collected. Performance parameters of HPV type restriction groupings were calculated, and sensitivity by individual HPV type Ct‐value limits were plotted. Results Among 2964 women who underwent primary HPV screening, 1293 (43.6%) tested HPV‐positive. Among women with HIV (WWH), HPV types 16/18/33 were associated with the greatest burden of CIN2+/CIN3+ (53%/56%). In WWH, grouping by HPV types separately reported in commercial assays (16/18/45) had low sensitivity (44% [CI: 36%–52%]) but high specificity (86% [CI: 84%–88%]) for CIN2+; 8‐type HPV restriction (16/18/31/33/35/45/52/58) improved sensitivity (79% [CI: 72%–86%]) and maintained reasonable specificity (67% [CI: 65%–70%]) for CIN2+. Similar results were seen in women without HIV. Ct‐limit setting for medium oncogenic HPV types (31,33,35,52,58) maintained a sensitivity of 72% in WWH while reducing over‐detection of non‐pathogenic HPV. Conclusion Eight‐type HPV restriction and Ct‐limit setting are promising strategies for improving the performance of primary HPV screening. A potential strategy to improve 8‐type HPV restriction would be to treat all with HPV 16/18/45; treat HPV 31/33/35/52/58 if below the type‐specific Ct limit and repeat HPV testing in 1‐year for other positive HPV results.

Triage of HPV positivity in a high HIV prevalence setting: A prospective cohort study comparing visual triage methods and HPV genotype restriction in Botswana

AbstractObjectiveGuidelines for effective triage following positive primary high‐risk human papillomavirus (HPV) screening in low‐ and middle‐income countries with high human immunodeficiency virus (HIV)‐prevalence have not previously been established. In the present study, we evaluated the performance of three triage methods for positive HPV results in women living with HIV (WLHIV) and without HIV in Botswana.MethodsWe conducted baseline enrollment of a prospective cohort study from February 2021 to August 2022 in South‐East District, Botswana. Non‐pregnant women aged 25 or older with an intact cervix and no prior diagnosis of cervical cancer were systematically consented for enrollment, with enrichment of the cohort for WLHIV. Those who consented completed a questionnaire and then collected vaginal self‐samples for HPV testing. Primary HPV testing for 15 individual genotypes was conducted using Atila AmpFire® HPV assay. Those with positive HPV results returned for a triage visit where all underwent visual inspection with acetic acid (VIA), colposcopy, and biopsy. Triage strategies with VIA, colposcopy and 8‐type HPV genotype restriction (16/18/31/33/35/45/52/58), separately and in combination, were compared using histopathology as the gold standard in diagnosing cervical intraepithelial neoplasia (CIN) 2 or worse (CIN2+).ResultsAmong 2969 women enrolled, 1480 (50%) tested HPV positive. The cohort included 1478 (50%) WLHIV; 99% were virologically suppressed after a mean of 8 years on antiretroviral therapy. In total, 1269 (86%) women had histopathology data for analysis. Among WLHIV who tested positive for HPV, 131 (19%) of 688 had CIN2+ compared with 71 (12%) of 581 in women without HIV. Screening by 8‐type HPV genotype restriction was more sensitive as triage to detect CIN2+ in WLHIV 87.79% (95% CI: 80.92–92.85) and women without HIV 85.92% (95% CI: 75.62–93.03) when compared with VIA (WLHIV 62.31% [95% CI: 53.39–70.65], women without HIV 44.29% [95% CI: 32.41–56.66]) and colposcopy (WLHIV 70.77% [95% CI: 62.15–78.41], women without HIV 45.71% [95% CI: 33.74–58.06]). However, 8‐type HPV genotype restriction had low specificity in WLHIV of 30.88% (95% CI: 27.06–34.90) and women without HIV 37.06% (95% CI: 32.85–41.41). These results were similar when CIN3+ was used as the outcome. When combining 8‐type HPV genotype restriction with VIA as the triage strategy, there was improved specificity to detect CIN2+ in WLHIV of 81.65% (95% CI: 78.18–84.79) but dramatically reduced sensitivity of 56.15% (95% CI: 47.18–64.84).ConclusionsEight‐type HPV genotype restriction is a promising component of effective triage for HPV positivity. However, novel triage strategies in LMICs with high HIV prevalence may be needed to avoid the trade‐off between sensitivity and specificity with currently available options.Clinical trials registrationThis study is registered on Clinicaltrials.gov no. NCT04242823, https://clinicaltrials.gov/ct2/show/NCT04242823.

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.

Primary HPV-based Cervical Cancer Screening Algorithms in Botswana

Primary high-risk human papillomavirus (HPV) testing has become first line screening for cervical cancer in high-income countries. The feasibility of this approach in low- and middle-income countries (LMICs) is less clear, as is the role of HPV testing among women living with human immunodeficiency virus (HIV). The proposed study seeks to evaluate the accuracy of cervical cancer screening algorithms using primary HPV testing followed by various forms of visual evaluation, including visual inspection with acetic acid (VIA), colposcopy and automated visual evaluation (AVE) for the detection of high-grade cervical dysplasia, using histology as the gold standard. We will validate the AmpFire Assay for HPV self-sampling in our setting. We will determine safe screening intervals in women living with HIV (WLHIV) in an HPV-based cervical cancer screening program and compare triage strategies for positive HPV results at WHO recommended screening intervals for WLHIV. We also seek to understand in-depth the attitudes, acceptability and preferences regarding cervical cancer screening, HPV testing, and self-sampling, for women in Botswana through interviews of a sub-set of women recruited for the cervical cancer screening study. Finally, we will analyze the cost of two-stage cervical cancer screening algorithms using high-risk HPV testing in Botswana.