Significance of HIV status in cervical cancer patients receiving curative chemoradiation therapy, definitive radiation alone, or palliative radiation in Botswana.

BACKGROUND: Cervical cancer associated with human papillomavirus has the highest cancer incidence and mortality for women in Botswana because of a high HIV prevalence and limited screening. This study investigates the significance of HIV on the overall survival (OS) of patients with locally advanced cervical cancer by various treatment categories (curative chemoradiation, definitive radiation [RT] alone, or palliative RT alone). METHODS: This study included patients diagnosed with cervical cancer between 2013 and 2020, prospectively enrolled in the Botswana Prospective Cancer Cohort. OS based on HIV status and completion of planned treatment regimen was estimated by the Kaplan-Meier method. Comparisons of 2-year OS by HIV status was performed by the log-rank test, univariate and multivariable Cox analyses adjusting for cancer stage, RT dose, number of chemotherapy cycles, and baseline hemoglobin levels. RESULTS: Of 1131 patients diagnosed with stage IB-IVB cervical cancer, 69.8% were women living with HIV (n = 789). For patients receiving curative chemoradiation, HIV status was not significantly associated with OS in unadjusted (p = .987) and adjusted (p = .578) analyses. For RT only treatment and definitive (high-dose) RT alone, HIV status was significantly associated with OS in unadjusted analysis (HR = 1.77, p = .002; HR = 1.95, p = .014), but not in adjusted analysis (p = .227, p = .73). For patients receiving palliative (low-dose) RT, HIV status was not associated with OS in unadjusted (p = .835) or adjusted analysis (p = .359). CONCLUSIONS: In Botswana, a resource-limited setting, HIV status had no significant effect on 2-year OS in patients with cervical cancer with well-managed HIV receiving chemoradiation, RT alone, or palliative RT. This demonstrates that patients living with HIV receiving antiretroviral treatment can receive clinically appropriate treatment with no evidence that HIV may lead to poorer outcomes.

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

OBJECTIVE: Guidelines 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. METHODS: We 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+). RESULTS: Among 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). CONCLUSIONS: Eight-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 REGISTRATION: This study is registered on Clinicaltrials.gov no. NCT04242823, https://clinicaltrials.gov/ct2/show/NCT04242823.

Patterns of care and outcomes for endometrial and ovarian cancers in botswana 2015-2021.

Purpose: Endometrial and ovarian cancers are leading causes of cancer death among women. However, there is little data on these patients from low- and middle-income countries including Botswana, a country in sub-Saharan Africa. This study reports data on demographics, treatment, and outcomes for patients with endometrial and ovarian cancer in Botswana. Methods: This prospective cohort study included all prospectively enrolled patients with endometrial or ovarian cancer who presented to Princess Marina or Gaborone Private Hospital between May 2015 and May 2021. Demographic, treatment, and survival data were analyzed. Results: 99 patients with endometrial and 38 patients with ovarian cancer were included. Median age at diagnosis was 64 for patients with endometrial cancer and 57 for patients with ovarian cancer. Just over half of patients with endometrial cancer (52.6%) presented with FIGO stages I and II, whereas most patients with ovarian cancer (65.8%) presented with stages III and IV. 24.2% of patients with endometrial cancer received chemotherapy, 32.3% received radiotherapy, 74.7% received surgical treatment, and 16.2% received no treatment; of patients with ovarian cancer, 42.1% received chemotherapy, 2.6% received radiotherapy, 52.6% received surgical treatment, and 31.6% of patients received no treatment. 1-and 2-year overall survival probabilities were 76.9% and 59.7% for patients with endometrial cancer and 62.8% and 43.7% for patients with ovarian cancer, respectively. Conclusion: This study demonstrates that a large proportion of patients with ovarian and endometrial cancer in Botswana are diagnosed at an advanced stage, and many do not receive standard-of-care treatment. Further inquiry is required to characterize challenges to diagnosis and treatment of ovarian and endometrial cancers in Botswana.

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

PURPOSE: Timely radiation treatment (RT) is critical in cervical cancer treatment, but patients in low- and middle-income countries (LMICs) in sub-Saharan Africa often face barriers that delay care. Time to care was benchmarked in a multidisciplinary team (MDT) setting in Botswana. METHODS: Time intervals between steps in care were recorded for 230 patients reviewed at MDT between January 2016 and July 2018. Associations between RT delay and overall survival (OS) were evaluated using Kaplan-Meier curves and multivariable Cox proportional hazards models. RESULTS: For patients who received RT (n = 187; 81.3%), the median biopsy to pathology reporting interval was 25 (IQR, 19-36) days and was 57 (IQR, 28-68) days for patients who did not (P = .003). Intervals in care did not differ between patients who did and did not receive RT. Among treated patients, the uppermost quartile interval from pathology reporting to RT initiation was ≥111 days and that from RT simulation to initiation was ≥12 days. Among patients receiving a RT dose of ≥65 Gy (n = 100), the delay from RT simulation to initiation of >12 days was associated with worse median OS (2.0 v 4.6 years; P = .048); this association trended toward, although did not meet, statistical significance on multivariable analysis (hazard ratio, 2.35; 95% CI, 0.95 to 5.85; P = .07). CONCLUSION: The MDT-coordinated care model allows for systematic benchmarking of the patient treatment cascade. Barriers to timely treatment exist for this cohort in Botswana, and RT delay may be associated with OS of patients receiving curative treatment. Interventions to accelerate the timing of the radiation oncology care cascade may improve clinical outcomes in this LMIC setting.

Comparison of the AmpFire® Multiplex HPV Assay to the Xpert® HPV Assay for detection of human papillomavirus and cervical disease in women with human immunodeficiency virus: a pragmatic performance evaluation.

BACKGROUND: Low- and middle-income countries (LMICs) account for nearly 85% of the global cervical cancer burden, yet have the least access to high-performance screening. International guidelines recommend human papillomavirus testing (HPV) as primary screening, yet implementation is inhibited by the cost of HPV testing. Atila AmpFire® HPV Assay (AmpFire) is both affordable and easy to use, and offers individual genotyping. The objective of this study was to compare the performance of the AmpFire HPV assay to the Xpert® HPV assay in detection of both HPV and clinically significant cervical disease. METHODS: We utilized stored cervical specimens from a prospective cohort study of women living with human immunodeficiency virus (HIV) in Botswana conducted from May to July 2018. Positive and negative percent agreement was calculated for the AmpFire and Xpert assays, as was detection of high-grade cervical dysplasia. RESULTS: 63 stored cervical specimens had detectable DNA after thawing and were included in the analysis. The positive percent agreement was 91.2% (95%CI 76.3-98.1) and negative percent agreement was 79.3% (95% CI 60.3-92.0). Six cases positive by AmpFire but negative by Xpert were HPV genotypes 35, 52 (n = 2), 58, 68, and co-infection with HPV 45 and 68. Both Xpert and AmpFire assays detected HPV in all 10 samples of women who had high-grade cervical dysplasia. CONCLUSIONS: The AmpFire HPV assay demonstrated excellent analytic performance in both detection of HPV and clinically significant cervical disease. AmpFire HPV is a promising option to increase access to affordable, type-specific HPV screening for cervical cancer in LMICs.

COVID-19 as a catalyst for reimagining cervical cancer prevention.

Cervical cancer has killed millions of women over the past decade. In 2019 the World Health Organization launched the Cervical Cancer Elimination Strategy, which included ambitious targets for vaccination, screening, and treatment. The COVID-19 pandemic disrupted progress on the strategy, but lessons learned during the pandemic - especially in vaccination, self-administered testing, and coordinated mobilization on a global scale - may help with efforts to achieve its targets. However, we must also learn from the failure of the COVID-19 response to include adequate representation of global voices. Efforts to eliminate cervical cancer will only succeed if those countries most affected are involved from the very start of planning. In this article we summarize innovations and highlight missed opportunities in the COVID response, and make recommendations to leverage the COVID experience to accelerate the elimination of cervical cancer globally.

Comparison of the AmpFire Multiplex HPV Assay to the Xpert HPV Assay for detection of human papillomavirus and cervical disease in women with human immunodeficiency virus: A pragmatic performance evaluation.

Background: Low- and middle-income countries (LMICs) account for nearly 85% of the global cervical cancer burden, yet have the least access to high-performance screening. International guidelines recommend human papillomavirus testing (HPV) as primary screening, yet implementation is inhibited by the cost of HPV testing.Atila AmpFire HPV Assay (AmpFire) is both affordable and easy to use, and offers individual genotyping. The objective of this study was to compare the performance of the AmpFire HPV assay to the Xpert HPV assay in detection of both HPV and clinically significant cervical disease. Methods: We utilized stored cervical specimens from a prospective cohortstudy of women living with human immunodeficiency virus (HIV) in Botswana conducted from May to July 2018. Positive and negative percent agreement was calculated for the AmpFire and Xpert assays, as was detection of high-grade cervical dysplasia. Results : 63 stored cervical specimens haddetectable DNA after thawing and were included in the analysis. The positive percent agreement was 91.2% (95%CI: 76.3-98.1) and negative percent agreement was 79.3% (95% CI: 60.3-92.0). Six cases positive by AmpFire but negative by Xpert were HPV genotypes 35, 52 (n=2), 58, 68, and co-infection with HPV 45 and 68. Both Xpert and AmpFire assays detected HPV in all 10 samples of women who had high-grade cervical dysplasia. Conclusions : The AmpFire HPV assay demonstrated excellent analytic performance in both detection of HPV and clinically significant cervical disease. AmpFire HPV is a promising option to increase access to affordable, type-specific HPV screening for cervical cancer in LMICs.

Cervical cancer screening in HIV-endemic countries: An urgent call for guideline change.

Women living with HIV (WLWH) are at an increased risk of developing HPV-related high grade cervical dysplasia and cervical cancer. Prior World Health Organization (WHO) screening guidelines recommended starting screening at age 30. We assessed characteristics of women diagnosed with cervical cancer to further inform and refine screening guidelines. We prospectively enrolled women diagnosed with cervical cancer from January 2015 to March 2020 at two tertiary hospitals in Gaborone, Botswana. We performed chi-square and ANOVA analyses to evaluate the association between age upon diagnosis and HIV status, CD4 count, viral load, and other sociodemographic and clinical factors. Data were available for 1130 women who were diagnosed with cervical cancer and 69.3% were WLWH. The median age overall was 47.9 (IQR 41.2-59.1), 44.6 IQR: 39.8 - 50.9) among WLWH, and 61.2 (IQR 48.6-69.3) among women living without HIV. There were 1.3% of women aged <30 years old, 19.1% were 30-39 and 37.2% were 40-49. Overall, 20.4% (n = 231) of cancers were in women <40 years. Age of cervical cancer diagnosis is younger in countries with higher HIV prevalence, like Botswana. Approximately 20% of the patients presented with cancer at <40 years of age and would have likely benefited from screening 10 years prior to cancer diagnosis to provide an opportunity for detection and treatment of pre-invasive disease.

Association of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection With Maternal Mortality and Neonatal Birth Outcomes in Botswana by Human Immunodeficiency Virus Status.

OBJECTIVE: To evaluate the combined association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human immunodeficiency virus (HIV) infection on adverse birth outcomes in an HIV-endemic region. METHODS: The Tsepamo Study abstracts data from antenatal and obstetric records in government maternity wards across Botswana. We assessed maternal mortality and adverse birth outcomes for all singleton pregnancies from September 2020 to mid-November 2021 at 13 Tsepamo sites among individuals with documented SARS-CoV-2 screening tests and known HIV status. RESULTS: Of 20,410 individuals who gave birth, 11,483 (56.3%) were screened for SARS-CoV-2 infection; 4.7% tested positive. People living with HIV were more likely to test positive (144/2,421, 5.9%) than those without HIV (392/9,030, 4.3%) (P=.001). Maternal deaths occurred in 3.7% of those who had a positive SARS-CoV-2 test result compared with 0.1% of those who tested negative (adjusted relative risk [aRR] 31.6, 95% CI 15.4-64.7). Maternal mortality did not differ by HIV status. The offspring of individuals with SARS-CoV-2 infection experienced more overall adverse birth outcomes (34.5% vs 26.6%; aRR 1.2, 95% CI 1.1-1.4), severe adverse birth outcomes (13.6% vs 9.8%; aRR 1.2, 95% CI 1.0-1.5), preterm delivery (21.4% vs 13.4%; aRR 1.4, 95% CI 1.2-1.7), and stillbirth (5.6% vs 2.7%; aRR 1.7 95% CI 1.2-2.5). Neonates exposed to SARS-CoV-2 and HIV infection had the highest prevalence of adverse birth outcomes (43.1% vs 22.6%; aRR 1.7, 95% CI 1.4-2.0). CONCLUSION: Infection with SARS-CoV-2 at the time of delivery was associated with 3.7% maternal mortality and 5.6% stillbirth in Botswana. Most adverse birth outcomes were worse among neonates exposed to both SARS-CoV-2 and HIV infection.

Feasibility and acceptability of an HPV self-testing strategy: lessons from a research context to assess for ability to implement into primary care at a national level in Botswana.

Background: The WHO strategy for cervical cancer elimination strives to achieve 70% coverage with high-performance cervical screening. While few low- and middle-income countries have achieved this, high-risk human papillomavirus (hrHPV) self-testing creates the possibility to rapidly upscale access to high-performance cervical screening across resource settings. However, effective hrHPV screening requires linkage to follow-up, which has been variable in prior studies. This study developed and tested an implementation strategy aimed at improving screening and linkage to follow-up care in South East District in Botswana. Methods: This study performed primary hrHPV self-testing; those with positive results were referred for a triage visit. Withdrawals for any reason, loss-to follow-up between hrHPV test and triage visit, and number of call attempts to give hrHPV results were also documented. Acceptability of the program to patients was measured as the proportion of patients who completed a triage visit when indicated, meeting the a priori threshold of 80%. Feasibility was defined as the proportion of participants receiving the results and attending follow-up. To assess the associations between participant characteristics and loss-to-follow-up we used log-binomial regressions to estimate risk ratios and 95% confidence intervals (CI). Results: Enrollment of 3,000 women occurred from February 2021 to August 2022. In total, 10 participants withdrew and an additional 33 were determined ineligible after consent, leaving a final cohort of 2,957 participants who underwent self-swab hrHPV testing. Half (50%) of participants tested positive for hrHPV and nearly all (98%) of participants received their hrHPV results, primarily via telephone.  Few calls to participants were required to communicate results: 2,397 (82%) required one call, 386 (13%) required 2 calls, and only 151 (5%) required 3-5 calls. The median time from specimen collection to participant receiving results was 44 days (IQR, 27-65). Of all hrHPV positive participants, 1,328 (90%) attended a triage visit. Discussion: In a large cohort we had low loss-to-follow-up of 10%, indicating that the strategy is acceptable. Telephonic results reporting was associated with high screening completion, required few calls to participants, and supports the feasibility of hrHPV self-testing in primary care followed by interval triage.

Stage and outcomes of invasive cervical cancer patients in Botswana: A prospective cohort study from 2013 to 2020.

Objective: To present the stage distribution, patterns of care, and outcomes of patients from Botswana with invasive cervical cancer, living with or without HIV. Methods: Between 2013 and 2020, women with cervical cancer were prospectively enrolled in an observational cohort study. Results: A total of 1,043 patients were enrolled; 69% were women living with HIV. The median age of the cohort was 47 years (interquartile range [IQR] 40-58 years), with women living with HIV presenting at a younger age compared to women without HIV (44 versus 61 years, p < 0.001). Among women living with HIV, the median CD4 count at the time of cancer diagnosis was 429.5 cells/µL (IQR 240-619.5 cells/µL), 13% had a detectable viral load, and 95% were on antiretroviral therapy. In regard to treatment, 6% (n = 58) underwent surgery, 33% (n = 341) received radiation therapy, 51% (n = 531) received chemoradiation, and 7% (n = 76) did not receive treatment. Stage distribution in the cohort was as follows: I 17% (n = 173), II 37% (n = 388), III 35% (n = 368), and IV 8% (n = 88). For all patients, 2-year OS was 67%. In multivariable Cox regression, worse OS was associated with stage: II (HR 1.91, p = 0.007), III (HR 3.99, p < 0.001), and IV (HR 5.06, p < 0.001) compared to stage I. Improved OS was associated with hemoglobin > 10 g/dL (HR 0.51, p < 0.001) compared to Hb ≤ 10 g/dL. Conclusions: Among women in Botswana with cervical cancer, most patients presented with stage II or III disease warranting radiation therapy or chemoradiation. While two-thirds of cervical cancer patients were women living with HIV, HIV did not impact OS.

Neoadjuvant chemotherapy and less invasive surgery for the management of early stage cervical cancer: A brief report from Botswana.

The majority of deaths from cervical cancer occur in low- and middle- income countries (LMICs). The standard of care for early-stage cervical cancer (FIGO 2018 IA2-IB1) is radical hysterectomy, a procedure performed by trained gynecologic oncologists. However, the lack of gynecologic oncologists in LMICs has required exploration into other methods of treatment for early-stage cervical cancer. A potential course of treatment for early-stage cervical cancer is neoadjuvant chemotherapy followed by simple hysterectomy and pelvic lymph node sampling, which can be performed by a general gynecologist. We gathered data for 8 women who underwent this method of treatment and found that cause-specific survival was 100% over a 3.5-year median follow-up. These findings support the exploration for this method of treatment for early-stage cervical cancer in LMICs, which would improve access to treatment for these women and hopefully reduce the high burden of cervical cancer related deaths in LMICs.

Patient perspectives on delays in cervical cancer screening and follow-up care in Botswana: a mixed methods study.

BACKGROUND: Delays in screening and timely diagnosis contribute significantly to global disparities in cervical cancer mortality in Botswana and other low- and middle-income countries, particularly those with high rates of HIV. Little is known about the modifiable factors shaping these delays from the perspectives of women themselves and how these perspectives may differ between those living with and without HIV. METHODS: From March-May 2019, we conducted a concurrent, mixed methods study of women receiving treatment for cervical cancer at a multidisciplinary oncology clinic in Botswana. Enrolled participants completed a one-time, concurrent semi-structured interview and structured questionnaire assessing patient characteristics, screening and HIV-related beliefs and knowledge, and barriers and facilitators to screening and follow-up care. Qualitative data were analyzed using directed content analysis guided by the Model of Pathways to Treatment and triangulated with quantitative questionnaire data to identify areas of convergence and divergence. Fisher's exact tests were used to explore associations between questionnaire data (e.g., screening knowledge) and HIV status. RESULTS: Forty-two women enrolled in the study, 64% of whom were living with HIV and 26% were diagnosed with stage III cervical cancer. Median age was 45 years (IQR 54-67) in those living with HIV and 64 years (IQR 42-53) in those living without. Overall screening rates before symptomatic disease were low (24%). Median time from most proximal screen to diagnosis was 52 median days (IQR 15-176), with no significant differences by HIV status. General screening knowledge was higher among those living with HIV versus those without (100% vs 73%; p < 0.05), but knowledge about HPV and other risk factors was low in both groups. Similar to questionnaire results, qualitative results indicate limited awareness of the need to be screened prior to symptoms as a central barrier to timely screening. Some participants also noted that delays in the receipt of screening results and fear also contributed to treatment delays. However, many participants also described myriad sources of social and tangible support that helped them to overcome some of these challenges. CONCLUSION: Interventions focused on increasing routine screening and supporting timely awareness and access to care are needed to reduce global disparities in cervical cancer.

Support for lowering cervical cancer screening age to 25 for women living with HIV: retrospective cross-sectional programmatic data from Botswana.

BACKGROUND: Women living with human immunodeficiency virus (HIV) tend to develop cervical cancer at a younger age than women without HIV. The World Health Organization's (WHO) 2021 guidelines for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention include a conditional recommendation for initiating screening at age 25 for women living with HIV (WLWH). This recommendation is based on low-certainty evidence, and WHO calls for additional data. We describe the association of age and HIV status with visual inspection with acetic acid (VIA) positivity and cervical intraepithelial neoplasia grade two or higher (CIN2+) in Botswana. METHODS: This was a retrospective cross-sectional study of 5714 participants aged 25 to 49 years who underwent VIA screening in a clinic mainly serving WLWH. VIA-positive women received cryotherapy if eligible or were referred for colposcopy and excisional treatment. Known cervical cancer risk factors, screening outcome, and histological results were extracted from the program database. We compared the proportions and association of VIA positivity and CIN2+ by age and HIV status. RESULTS: The median age was 35 years [IQR 31-39], and 18% of the women were aged 25-29. Ninety percent were WLWH; median CD4 count was 250 cells/µL [IQR 150-428], and 34.2% were on anti-retroviral treatment (ART). VIA-positivity was associated with younger age (OR 1.48, CI 1.28, 1.72 for 25-29 years vs. 30-49 years), and HIV-positivity (OR 1.85, CI 1.51, 2.28). CIN2+ was only associated with HIV-positivity (OR 6.12, CI 3.39, 11.10), and proportions of CIN2+ were similar for both age groups in WLWH (69.1% vs. 68.3%). CONCLUSIONS: Younger WLWH in Botswana had a significant burden of CIN2+. This finding further supports lowering the screening age for WLWH from 30 to 25.

HPV prevalence among young adult women living with and without HIV in Botswana for future HPV vaccine impact monitoring.

INTRODUCTION: In 2015, Botswana introduced quadrivalent human papillomavirus (HPV) vaccine for girls aged 9-13 years. To establish a baseline HPV prevalence for future HPV vaccine impact monitoring, we evaluated HPV prevalences among the youngest unvaccinated women in Botswana and compared HPV prevalences among women living with HIV (WLHIV) and without HIV. METHODS: Women aged 18-22 years were recruited from the University of Botswana and HIV clinics in Gaborone from October 2019-January 2021. Demographic and behavioral characteristics were self-reported during structured interviews; HIV clinical characteristics were abstracted from medical charts. Self-collected vaginal swabs were tested for 28 HPV types using Seegene Anyplex II HPV28. We compared prevalence of any HPV, high risk (HR)-HPV, and quadrivalent HPV vaccine types (HPV6/11/16/18) among WLHIV and women without HIV and evaluated risk factors for prevalence of HR-HPV. RESULTS: A total of 306 WLHIV and 500 women without HIV were recruited. Compared to women without HIV, WLHIV were more likely to be sexually experienced (86.6% versus 74.4%) and have ≥ 3 lifetime sex partners (55.3% versus 27.8%). All HPV type prevalences were significantly higher among WLHIV compared to women without HIV, including prevalence of any HPV (82.7% versus 63.0%), HR-HPV (72.9% versus 53.8%), and quadrivalent vaccine HPV types (34.3% versus 21.0%). Among WLHIV, there were no differences between those perinatally and non-perinatally infected for HPV prevalences, number of HPV types detected, CD4 count, or viral load. CONCLUSIONS: Over one-third of WLHIV and nearly a quarter of those without HIV had vaccine-type HPV detected. This study supports need for the national HPV vaccination program in Botswana and provides important baseline data for future evaluation of impact of the program.

Progress and challenges in human papillomavirus and cervical cancer in southern Africa.

PURPOSE OF REVIEW: Although cervical cancer is preventable, it is the leading cancer among women in southern Africa. The association of high-risk human papillomavirus (HR-HPV) with almost all invasive cervical cancers has led to the development of effective primary and secondary prevention measures. This review focuses on updated and new evidence of the epidemiology of HPV and HPV-based secondary prevention in southern Africa. RECENT FINDINGS: HR-HPV prevalence in southern Africa differs between regions, and varies most by HIV prevalence and age. HR-HPV prevalence among women living with HIV (WLWH) is reported between 29 and 59.7%, and between 16.2 and 25.2% among women without HIV. HPV16 is the most common HR-HPV type present in invasive cervical cancers in the region; and vaccination may potentially prevent approximately 80% of these cancers. Concerning preliminary data suggests faster development of new cervical precancer within a short follow-up period. SUMMARY: We need tools that identify the small number of women with precancer from the many with transient HR-HPV infection in southern Africa. The high-volume of test-positive women leads to challenges in managing triage in a HR-HPV-based screening program. Longitudinal data from the entire region is urgently needed to guide effective implementation of HPV-based screening programs.

Anti-hypertensive use for non-severe gestational hypertension in Botswana: A case-control study.

OBJECTIVE: The fetal risks and benefits of antihypertensives to treat gestational hypertension in pregnancy are understudied, particularly in low- and middle-income countries. METHODS: We performed a nested case-control study within a retrospective cohort of obstetrical patients in Botswana from 2014 to 2019. We included women carrying singletons who developed new onset non-severe hypertension (140-159 mm Hg systolic or 90-109 mm Hg diastolic blood pressure) after 20 weeks of pregnancy. Cases were defined as women with either small-for-gestational-age (SGA) infants or stillbirth, analyzed separately; controls were otherwise similar women without the adverse outcome in each analysis. RESULTS: We identified 1932 cases of SGA (7925 controls) and 316 cases of stillbirth (9619 controls). Cases with SGA were more likely to have used an anti-hypertensive than controls (33% vs 29%, adjusted odds ratio [aOR] 1.28, 95% confidence interval [CI] 1.15-1.43). Cases with stillbirth were more likely to have used an anti-hypertensive than controls (42% versus 29%, aOR 1.45, 95% CI 1.14-1.83). CONCLUSION: Anti-hypertensive use for new-onset gestational hypertension was associated with an increased risk of having an SGA infant or a stillbirth among women who never developed severe hypertension. These data support conduct of a randomized clinical trial to determine the appropriate use of anti-hypertensives in non-severe gestational hypertension.

Prevalence and outcomes of twin pregnancies in Botswana: a national birth outcomes surveillance study.

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.