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.

Distance to Multidisciplinary Team Clinic in Gaborone, Botswana, and Stage at Cervical Cancer Presentation for Women Living With and Without HIV.

PURPOSE: Cervical cancer is the leading cause of cancer death for women in Botswana. Barriers in access to cancer care can lead to later stages at diagnosis and increased mortality. This study evaluated access, defined as travel time from a patient's residential village to a multidisciplinary team clinic in Gaborone, with stage of cervical cancer at presentation. In addition, because of the high HIV prevalence in Botswana, we explored the association between travel time and HIV status. METHODS: Eligible patients with cervical cancer presenting to the multidisciplinary team between 2015 and 2020 were included. Data were abstracted from questionnaires and hospital records. Google Maps was used to calculate travel time. Multinomial regression was used to examine travel time and cancer stage, and multivariable logistic regression was used to investigate travel time and HIV status. RESULTS: We identified 959 patients with cervical cancer of which 70.1% were women living with HIV. The median travel time was approximately 2 hours. Using a reference group of stage I disease and a travel time of < 1 hour, the odds of presenting with stage II increased for patients traveling 3-5 hours (adjusted odds ratio [OR], 2.00; 95% CI, 1.14 to 3.52) and > 5 hours (OR, 2.19; 95% CI, 1.15 to 4.19). There were no significant associations for stage III. For stage IV disease, the odds were increased for patients traveling 3-5 hours (OR, 2.93; 95% CI, 1.26 to 6.79) and > 5 hours (adjusted OR, 4.05; 95% CI, 1.62 to 10.10). In addition, the odds of patients presenting living with HIV increased with increasing travel time (trend test = 0.004). CONCLUSION: This study identified two potential factors, travel time and HIV status, that influence access to comprehensive cervical cancer care in Botswana.

Evaluating the geographic distribution of cervical cancer patients presenting to a multidisciplinary gynecologic oncology clinic in Gaborone, Botswana.

OBJECTIVE: In Botswana, cervical cancer is the leading cause of cancer death for females. With limited resources, Botswana is challenged to ensure equitable access to advanced cancer care. Botswana's capital city, Gaborone, houses the only gynecologic oncology multi-disciplinary team (MDT) and the one chemoradiation facility in the country. We aimed to identify areas where fewer women were presenting to the MDT clinic for care. METHODS: This cross-sectional study examined cervical cancer patients presenting to the MDT clinic between January 2015 and March 2020. Patients were geocoded to residential sub-districts to estimate age-standardized presentation rates. Global Moran's I and Anselin Local Moran's I tested the null hypothesis that presentation rates occurred randomly in Botswana. Community- and individual-level factors of patients living in sub-districts identified with higher (HH) and lower (LL) clusters of presentation rates were examined using ordinary least squares with a spatial weights matrix and multivariable logistic regression, respectively, with α level 0.05. RESULTS: We studied 990 patients aged 22-95 (mean: 50.6). Presentation rates were found to be geographically clustered across the country (p = 0.01). Five sub-districts were identified as clusters, two high (HH) sub-district clusters and three low (LL) sub-district clusters (mean presentation rate: 35.5 and 11.3, respectively). Presentation rates decreased with increased travel distance (p = 0.033). Patients residing in LL sub-districts more often reported abnormal vaginal bleeding (aOR: 5.62, 95% CI: 1.31-24.15) compared to patients not residing in LL sub-districts. Patients in HH sub-districts were less likely to be living with HIV (aOR: 0.59; 95% CI: 0.38-0.90) and more likely to present with late-stage cancer (aOR: 1.78; 95%CI: 1.20-2.63) compared to patients not in HH sub-districts. CONCLUSIONS: This study identified geographic clustering of cervical cancer patients presenting for care in Botswana and highlighted sub-districts with disproportionately lower presentation rates. Identified community- and individual level-factors associated with low presentation rates can inform strategies aimed at improving equitable access to cervical cancer care.

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.

Retrospective cohort analysis of prescription patterns of cancer medications during periods of drug stockouts in Botswana.

OBJECTIVE: Cancer drug stockouts occur at high frequencies globally, however, their effects on treatment are understudied in sub-Saharan Africa (SSA). We aimed to determine whether causes of suboptimal cancer treatment prescriptions differed between periods of stockout and full treatment supply. DESIGN: A retrospective cohort study of systemic therapy prescriptions for patients diagnosed with the twelve most common solid tumour cancers treated in 2016. SETTING: Princess Marina Hospital in Gaborone, Botswana. PARTICIPANTS: Patients in the retrospective cohort who experienced any suboptimal treatment events, defined as ≥7 days delay or switch from guideline-concordant initiated therapy. PRIMARY AND SECONDARY OUTCOME MEASURES: Frequency of delays and patterns of prescription changes for specific regimens and cancer types. RESULTS: 167/378 patients contributed to 320 suboptimal events (115 therapy switches, 167 delays and 38 events with both), over 1452 total chemotherapy cycles received. Events during stockout were 43% delays, 43% switches and 14% both during stockout periods and 67.2% delays, 24.4% switches and 8.4% both during non-stockout periods (p<0.001). Majority of switches involved de-escalation of initially prescribed guideline-recommended regimens in patients with breast cancer, Kaposi sarcoma and patients with colorectal cancer, which occurred more frequently during periods of drug stockouts. Among patients with breast cancer, substitution of docetaxel for paclitaxel event occurred exclusively during paclitaxel drug stockout. Delays of ≥7 days events were most frequent in breast cancer patients receiving paclitaxel during stockout, and combination doxorubicin and cyclophosphamide even during periods of non-stockout. CONCLUSIONS: The aetiology of suboptimal events differed during stockout and non-stockout periods. Prescription patterns that involved de-escalation of initiated therapy and substitution of paclitaxel with docetaxel occurred frequently during periods of drug stockout. Further research needs to be conducted to understand the impact of stockout on survival and barriers to maintaining essential cancer medicines supplies in SSA, and the factors driving frequent delays in therapy delivery.

Clinical and sociodemographic factors associated with late stage cervical cancer diagnosis in Botswana.

BACKGROUND: Cervical cancer is the leading cause of female cancer mortality in Botswana with the majority of cervical cancer patients presenting with late-stage disease. The identification of factors associated with late-stage disease could reduce the cervical cancer burden. This study aims to identify potential patient level clinical and sociodemographic factors associated with a late-stage diagnosis of cervical cancer in Botswana in order to help inform future interventions at the community and individual levels to decrease cervical cancer morbidity and mortality. RESULTS: There were 984 women diagnosed with cervical cancer from January 2015 to March 2020 at two tertiary hospitals in Gaborone, Botswana. Four hundred forty women (44.7%) presented with late-stage cervical cancer, and 674 women (69.7%) were living with HIV. The mean age at diagnosis was 50.5 years. The association between late-stage (III/IV) cervical cancer at diagnosis and patient clinical and sociodemographic factors was evaluated using multivariable logistic regression with multiple imputation. Women who reported undergoing cervical cancer screening had lower odds of late-stage disease at diagnosis (OR: 0.63, 95% CI 0.47-0.84) compared to those who did not report screening. Women who had never been married had increased odds of late-stage disease at diagnosis (OR: 1.35, 95% CI 1.02-1.86) compared to women who had been married. Women with abnormal vaginal bleeding had higher odds of late-stage disease at diagnosis (OR: 2.32, 95% CI 1.70-3.16) compared to those without abnormal vaginal bleeding. HIV was not associated with a diagnosis of late-stage cervical cancer. Rural women who consulted a traditional healer had increased odds of late-stage disease at diagnosis compared to rural women who had never consulted a traditional healer (OR: 1.61, 95% CI 1.02-2.55). CONCLUSION: Increasing education and awareness among women, regardless of their HIV status, and among providers, including traditional healers, about the benefits of cervical cancer screening and about the importance of seeking prompt medical care for abnormal vaginal bleeding, while also developing support systems for unmarried women, may help reduce cervical cancer morbidity and mortality in Botswana.

Impact of Essential Medicine Stock Outs on Cancer Therapy Delivery in a Resource-Limited Setting.

PURPOSE: Essential cancer medicine stock outs are occurring at an increasing frequency worldwide and represent a potential barrier to delivery of standard therapy in patients with cancer in low- and middle-income countries. The objective of this study was to measure the impact of cancer medicine stock outs on delivery of optimal therapy in Botswana. METHODS: We conducted a retrospective analysis of patients with common solid tumor malignancies who received systemic cancer therapy in 2016 at Princess Marina Hospital, Gaborone, Botswana. Primary exposure was the duration of cancer medicine stock out during a treatment cycle interval, when the cancer therapy was intended to be administered. Mixed-effects univariable and multivariable logistic regression analyses were used to calculate the association of the primary exposure, with the primary outcome, suboptimal therapy delivery, defined as any dose reduction, dose delay, missed cycle, or switch in intended therapy. RESULTS: A total of 378 patients met diagnostic criteria and received systemic chemotherapy in 2016. Of these, 76% received standard regimens consisting of 1,452 cycle intervals and were included in this analysis. Paclitaxel stock out affected the highest proportion of patients. In multivariable mixed-effects logistic regression, each week of any medicine stock out (odds ratio, 1.9; 95% CI, 1.7 to 2.13; P < .001) was independently associated with an increased risk of a suboptimal therapy delivery event. CONCLUSION: Each week of cancer therapy stock out poses a substantial barrier to receipt of high-quality cancer therapy in low- and middle-income countries. A concerted effort between policymakers and cancer specialists is needed to design implementation strategies to build sustainable systems promoting a reliable supply of cancer medicines.