Publications

OBJECTIVES: Vulvar cancer is a rare gynecological malignancy. However, the incidence of human papillomavirus (HPV)-associated vulvar disease is increasing, particularly in low- and middle-income countries. HIV infection is associated with an increased risk of HPV-associated vulvar cancer. We evaluated treatment patterns and survival outcomes in a cohort of vulvar cancer patients in Botswana. The primary objective of this study was to determine overall survival and the impact of treatment modality, stage, and HIV status on overall survival.

METHODS: Women with vulvar cancer who presented to oncology care in Botswana from January 2015 through August 2019 were prospectively enrolled in this observational cohort study. Demographics, clinical characteristics, treatment, and survival data were collected. Factors associated with survival including age, HIV status, stage, and treatment were evaluated.

RESULTS: Our cohort included 120 women with vulvar cancer. Median age was 42 (IQR 38-47) years. The majority of patients were living with HIV (89%, n=107) that was well-controlled on antiretroviral treatment. Among women with HIV, 54.2% (n=58) were early stage (FIGO stage I/II). In those without HIV, 46.2% (n=6) were early stage (stage I/II). Of the 95 (79%) patients who received treatment, 20.8% (n=25) received surgery, 67.5% (n=81) received radiation therapy, and 24.2% (n=29) received chemotherapy, either alone or in combination. Median follow-up time of all patients was 24.7 (IQR 14.2-39.1) months and 2- year overall survival for all patients was 74%. Multivariate analysis demonstrated improved survival for those who received surgery (HR 0.26; 95% CI 0.08 to 0.86) and poor survival was associated with advanced stage (HR 2.56; 95% CI 1.30 to 5.02). Survival was not associated with HIV status.

CONCLUSIONS: The majority of women with vulvar cancer in Botswana are young and living with HIV infection. Just under half of patients present with advanced stage, which was associated with worse survival. Improved survival was seen for those who received surgery.

OBJECTIVES: This study aims to evaluate the prevalence and outcome of twin pregnancies in Botswana.

SETTING: The Tsepamo Study conducted birth outcomes surveillance at 8 government-run hospitals ( 45% of all births in Botswana) from August 2014 to June 2018 and expanded to 18 hospitals ( 70% of all births in Botswana) from July 2018 to March 2019.

PARTICIPANTS: Data were collected for all live-born and stillborn in-hospital deliveries with a gestational age (GA) greater than 24 weeks. This analysis included 117 593 singleton and 3718 twin infants (1859 sets (1.6%)) born to 119 477 women between August 2014 and March 2019 and excluded 73 higher order multiples (23 sets of triplets and 1 set of quadruplets).

OUTCOMES MEASURED: Our primary outcomes were preterm delivery (<37 weeks GA), very preterm delivery (<32 weeks GA) and stillbirth (APGAR (Appearance, Pulse, Grimace, Activity, Respiration) score of 0, 0, 0).

RESULTS: Women with twin pregnancies had a similar median number of antenatal care visits (9 vs 10), but were more likely to deliver in a tertiary centre (54.8% vs 45.1%, p<0.001) and more likely to have a cesarean-section (54.6% vs 22.0%, p<0.001) than women with singletons. Compared with singletons, twin pregnancies had a higher risk of preterm delivery (<37 weeks GA) (47.6% vs 16.7%, adjusted risk ratio (aRR) 2.8, 95% CI 2.7 to 2.9) and very preterm delivery (<32 weeks) (11.8% vs 4.0%, aRR 3.0 95% CI 2.6 to 3.4). Among all twin pregnancies, 128 (6.9%) had at least one stillborn infant compared with 2845 (2.4%) stillbirths among singletons (aRR 2.8, 95% CI 2.3 to 3.3).

CONCLUSION: Adverse birth outcomes are common among twins in Botswana, and are often severe. Interventions that allow for earlier identification of twin gestation and improved antenatal management of twin pregnancies may improve infant and child survival.

BACKGROUND: Recent data suggests clinically significant weight gain among non-pregnant HIV-positive adults after starting dolutegravir-based ART (DTG). Excess or insufficient weight gain in pregnancy could adversely impact pregnancy outcomes, but data for pregnant women receiving DTG are limited.

METHODS: The Tsepamo Study captured data at delivery sites in Botswana from 2014 to 2019. HIV testing, HIV treatment information, and weight measurements during antenatal care were abstracted from the maternity obstetric record at delivery. HIV-positive women initiating DTG or efavirenz-based ART (EFV) between conception and 17 weeks gestation and HIV-uninfected women first presenting for antenatal care before 17 weeks gestation were included. We evaluated weekly weight gain, total 18-week weight gain, excess weight gain (>0.59 kg/week), insufficient weight gain (<0.18 kg/week), and weight loss between 18±2 and 36±2 weeks gestation, adjusting for demographic and clinical variables.

FINDINGS: Baseline characteristics were similar by exposure group, including pre-pregnancy and early pregnancy weight. Compared with EFV, mean weekly weight gain between 18 and 36 weeks gestation was 0.05 (95% CI 0.03, 0.07) kg/week higher for women initiating DTG and 0.12 (0.10, 0.14) kg/week higher for HIV-uninfected women. Mean 18-week weight gain was 1.05 (95% CI 0.61, 1.49) kg higher for women initiating DTG and 2.31 (1.85, 2.77) kg higher for HIV-uninfected women, compared with EFV. Women initiating DTG were more likely to gain excess weight but less likely to gain insufficient weight or lose weight than women initiating EFV.

INTERPRETATION: Women initiating DTG compared with EFV during pregnancy gained more weight between 18 and 36 weeks gestation. Neither group gained as much weight as HIV-uninfected women. Initiating DTG compared with EFV during pregnancy could increase the risk of excess weight gain but decrease the risk of insufficient weight gain and weight loss, which could have positive and negative consequences in pregnancy. Our findings are consistent with prior studies in non-pregnant adults.

BACKGROUND: Cervical cancer is the leading cause of cancer death in Sub-Saharan Africa. The risk of developing cancer is increased for women living with human immunodeficiency virus (HIV) infection. It is unknown which factors predict the initiation of curative chemoradiotherapy (CRT) in resource-limited settings and whether HIV is associated with initiating curative CRT in settings with a high HIV burden.

METHODS: All women living with and without HIV infection who were initiating curative and noncurative CRT for locally advanced cervical cancer in Botswana were prospectively enrolled in an observational study. The factors associated with receiving CRT were evaluated in all patients and the subgroup of women living with HIV.

RESULTS: Of 519 enrolled women, 284 (55%) initiated CRT with curative intent. The curative cohort included 200 women (70.4%) who were living with HIV and had a median CD4 count of 484.0 cells/μL (interquartile range, 342.0-611.0 cells/μL). In the noncurative cohort, 157 of 235 women (66.8%) were living with HIV and had a median CD4 count of 476.5 cells/μL (interquartile range, 308.0-649.5 cells/μL). HIV status was not associated with initiating curative CRT (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.58-1.56). The factors associated with receiving curative CRT treatment on multivariable analysis in all patients included baseline hemoglobin levels ≥10 g/dL (OR, 1.80; 95% CI, 1.18-2.74) and stage I or II versus stage III or IV disease (OR, 3.16; 95% CI, 2.10-4.75). Women aged >61 years were less likely to receive curative treatment (OR, 0.43; 95% CI, 0.24-0.75). Among women who were living with HIV, higher CD4 cell counts were associated with higher rates of CRT initiation.

CONCLUSIONS: The initiation of CRT with curative intent does not depend on HIV status. Significant predictors of CRT initiation include baseline hemoglobin level, disease stage, and age.

OBJECTIVE: To design an Obstetrics and Gynecology (OBGYN) residency elective in global health that meets ACGME standards and simultaneously promotes health equity.

DESIGN: A 4-week elective was established for US residents in a high-volume African district hospital that served as a site for OBGYN rotations for the national internship training program. Clear clinical, operative, and teaching requirements were delineated for US OBGYN residents. Resident formal didactic outputs were incorporated into the intern OBGYN curriculum. The program was evaluated through assessment of resident experience and contribution to local training, as well as assessment of intern competency in OBGYN.

SETTING: Scottish Livingstone Hospital, a public district hospital in Molepolole, Botswana.

PARTICIPANTS: Second- to fourth-year OBGYN residents from US training programs, working with Batswana medical interns under on-site faculty supervision.

RESULTS: From May 2016 to June 2018, 18 residents from 9 US OBGYN residency programs participated in the elective. Under supervision, US residents performed 116 major and 77 minor gynecologic surgeries, and teach-assisted Batswana interns and medical officers in 76 cesarean deliveries. Residents led or contributed significantly to 25 didactic education sessions as part of the formal intern OBGYN curriculum. During this period, 24 Batswana interns rotated through the hospital's department of OBGYN, and all 24 trainees met required OBGYN competencies prior to completing their internship.

CONCLUSIONS: Matching US resident demand for global health experiences to equitable global health programming while maintaining ACGME training guidelines poses a challenge to OBGYN residency training programs. This elective provides a model OBGYN global health elective that addresses host-identified needs, broadens residents' skills, and meets standards for postgraduate OBGYN training. Purposeful global health electives for US residents embedded in longitudinal programs provide an opportunity for residents to contribute to broader global health efforts that promote health equity.

OBJECTIVE: To evaluate the performance of cervical cancer screening algorithms for women living with human immunodeficiency virus (HIV), using primary high-risk human papillomavirus (HPV) testing followed by cytology, visual inspection with acetic acid, or colposcopy.

METHODS: We conducted a prospective cohort study of women living with HIV in Botswana. All participants underwent high-risk HPV testing. Participants with positive high-risk HPV test results underwent cytology, visual inspection with acetic acid, colposcopy, and biopsy. Participants with negative high-risk HPV test results also underwent cytology. Histopathology was the reference standard for determination of preinvasive cervical disease and cervical cancer. Sensitivity, specificity, positive predictive value (PPV), negative predictive value, and likelihood ratios (LR) of high-risk HPV-based two-stage screening algorithms were calculated.

RESULTS: Among 300 women screened, 88 (29%) had a positive high-risk HPV test result, and 29 of the 88 (35%) women who tested positive for high-risk HPV had CIN 2 or higher on histopathology. High-risk HPV followed by colposcopy resulted in a sensitivity of 83%, specificity of 49%, PPV of 47%, LR+ of +1.6, and LR- of -0.4. High-risk HPV followed by visual inspection with acetic acid resulted in a reduced sensitivity of 59%, specificity of 49%, PPV of 39%, LR+ of +1.2, and LR- of -0.8. High-risk HPV testing followed by cytology also resulted in a reduced sensitivity of 62%, specificity of 77%, PPV of 60%, LR+ of +2.7, and LR- of -0.5. Stratification by HPV 16/18/45 did not improve performance of the algorithms.

CONCLUSION: In a high-risk population with HIV, high-risk HPV testing followed by colposcopy demonstrated the highest sensitivity and PPV in detecting high-grade cervical dysplasia. Allocating resources to colposcopy in resource-limited settings may be more effective than other screening strategies.

BACKGROUND:: In Botswana, where HIV prevalence remains high, cervical cancer is the leading cause of cancer deaths in women. Multiple organizations recommend high-risk human papillomavirus (hr-HPV) testing as a screening tool, however, high coverage may not be feasible with provider-collected samples. We conducted the first assessment of self- versus provider-collected samples for hr-HPV testing in HIV-positive women in Botswana and report prevalence of hr-HPV and histological outcomes.

METHODS:: We recruited HIV-positive women ≥25 years attending an HIV clinic in Gaborone. Self- and provider-collected samples from participants were tested for hr-HPV using Cepheid GeneXpert. Women testing positive for any hr-HPV returned for colposcopy. We used unweighted κ statistics to determine hr-HPV agreement.

RESULTS:: Thirty-one (30%) of 103 women tested positive for any hr-HPV. The most common genotypes were HPV 31/33/35/52/58. Overall agreement between self- and provider-collected samples for any hr-HPV was 92% with a κ of 0.80. Ten of the 30 hr-HPV positive women attending colposcopy had CIN 2+ (33%).

CONCLUSIONS:: In this HIV-positive population, hr-HPV prevalence was 30%, with excellent agreement between self and provider samples. Self-sampling may play an important role in screening programs in high HIV burden settings with limited resources like Botswana.