Rohini K. Bhatia

Overcoming Logistical Barriers to Conducting Collaborative Clinical Research Between a High-Income Country and a Low- and Middle-Income Country

PURPOSE Building equitable research collaborations between high-income countries (HICs) and low- and middle-income countries (LMICs) requires effective coordination among international ethical review committees, which is often logistically challenging. This case report presents the insights gained when acquiring ethical approval for a cervical cancer research program conducted jointly by the University of Pennsylvania and the University of Botswana. METHODS We conducted a descriptive case study of the Ipabalele project, a 6-year HIC-LMIC partnership involving three complex research protocols that required approvals by multiple distinct ethical bodies. We analyzed various challenges affecting review procedures, timelines, and staffing. We then documented strategies employed in Ipabalele and other global initiatives to strengthen ethical review processes and build research capacity in LMICs. RESULTS In Ipabalele, ethical approvals were initially delayed by 2 years because of fragmented review processes with variable timelines and conflicting recommendations. Innovations to the process included centralizing institutional review board oversight within Botswana, implementing joint virtual meetings among review bodies, enhancing digital infrastructure, and streamlining research staffing and communication. CONCLUSION By providing practical strategies, this study highlights how empowered local leadership, centralized review processes, joint review mechanisms, and intentional capacity building can overcome logistical barriers in multinational ethical review.

Characterization of HPV subtypes in invasive cervical cancer in Botswana patients using a pan-pathogen microarray technology

Human papillomavirus (HPV) plays a significant role in the development of cervical cancers in the setting of co-infection with HIV. Botswana has a high prevalence of HIV and cervical cancer. In this study, we investigated the distribution of HPV subtypes in cervical cancer biopsy samples from patients in Botswana using a highly sensitive pan-pathogen microarray technology, PathoChip, to detect both high- (HR-HPV) and low-risk HPV (LR-HPV) subtypes in women living with HIV (WLWH) and women living without HIV. We analyzed samples from 168 patients, of which 73% (n = 123) were WLWH with a median CD4 count of 479.5 cells/μL. Five HR-HPV subtypes were detected in the cohort: HPV 16, 18, 26, 34, and 53. The most prevalent subtypes were HPV 26 (96%) and HPV 34 (92%); 86% of WLWH (n = 106) had co-infection with four or more HR-HPV subtypes compared to 67% (n = 30) of women without HIV (p 200 cells/μL and HIV-negative patients. Although the majority of cervical cancer specimens in this cohort were determined to have multiple HPV infections, the most prevalent HR-HPV subtypes (HPV 26 and HPV34) found in these cervical cancer samples are not covered in the current HPV vaccines. Though no conclusions can be made on the direct carcinogenicity of these subtypes the results do underlie the need for continued screening for prevention of cervical cancer.

Impact of the COVID-19 Pandemic on Cervical Cancer Treatment Delays in Botswana

PURPOSE Although the majority of cervical cancer cases are in sub-Saharan Africa, little is known regarding how the COVID-19 pandemic affected cancer care in this context. Drawing from robust longitudinal data, this study aimed to assess cervical cancer treatment patterns in Botswana before and during the pandemic. METHODS Longitudinal clinical and patient-reported data from a cohort of over 1,000 patients seen at a gynecologic oncology multidisciplinary team clinic in Botswana were used to evaluate treatment initiation patterns before (April 2018-December 2019) and during (April 2020-December 2021) the pandemic. The primary outcome was timeliness of treatment, defined as the number of days between the patient's first clinic visit and treatment initiation date, and categorized as timely (≤30 days), delayed (>30 days), or no treatment. The primary exposure was time of visit (pre–COVID-19 v COVID-19), defined by the month of the clinic visit. RESULTS Of the 559 patients with cervical cancer diagnosed during the study period, 336 were seen pre–COVID-19, and 223 were seen during the COVID-19 period. During the pandemic, a higher proportion of patients experienced treatment delays (66.4%) or received no treatment (24.2%), compared with the pre–COVID-19 period (35.7% and 9.8%, respectively; P < .001). Multivariable regression models indicated that patients seen during the pandemic were 10 times more likely to experience treatment delays (adjusted odds ratio [aOR], 10.01 [95% CI, 5.69 to 17.62]) and 14 times more likely to receive no treatment (aOR, 14.16 [95% CI, 7.14 to 28.10]). CONCLUSION The pandemic exacerbated treatment delays for patients with cervical cancer in Botswana. There is a need for evidence-based strategies to address these treatment delays, considering the disproportionate burden of disease and persistent disparities in access to care in Botswana and other low- and middle-income countries.

Cervical cancer treatment outcomes and survival in Botswana by human immunodeficiency virus status: Ipabalele study results

Abstract Background Cervical cancer is a leading morbidity/mortality cause, frequently co-occurring with human immunodeficiency virus (HIV) positivity, in Botswana. We examined long-term outcomes for Ipabalele study participants receiving curative chemoradiation for locally advanced cervical cancer (2015-2019) by HIV status. Methods Clinical and outcome data were collected at baseline, treatment completion, and 3 months thereafter. Patients were followed for up to 5 years. Overall survival (OS) was evaluated using Kaplan-Meier curves and Cox regression. Results The cohort comprised 295 patients (73.8% with HIV, younger at diagnosis [P < .001]) followed for a median of 44.2 months. Complete response was seen in 217/278 (76.1%) patients. Two- and 5-year OS rates were 73.4% and 59.9%, respectively, with no difference by HIV status. OS was associated negatively with advanced disease stage (III: hazard ratio [HR] 13.23, P < .001; IV: HR 7.8, P = .008) and positively with increased radiation (HR 0.977, P = .0005) and chemotherapy (HR 0.85, P = .005). Clinical response was associated negatively with advanced disease (IV: HR 0.113, P = .002) and positively with increased radiation (P = .009). Toxicity did not differ by HIV status. The most common grade-≥-2 non-hematological and hematological toxicities were radiation dermatitis (39.8%) and reduced white blood cell count (66.05%), respectively. Conclusions In this cervical cancer cohort with good HIV status control, treatment outcomes and OS were associated with disease and treatment factors, not the HIV status. Early screening and education regarding treatment protocols are crucial to improve cervical cancer outcomes in Botswana.