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Elevated serum squamous cell antigen (SCCAg) has been previously correlated with poor survival, extensive tumor involvement, and recurrence for cervical cancer. Failure of serum SCCAg to normalize after treatment completion has also been studied as a poor prognostic indicator. This is the first study describing the association of SCCAg with stage and outcomes in patients diagnosed with cervical cancer in Botswana, in a population with a majority of women who are living with HIV (WLWH). Patients with histologically confirmed cervical cancer were enrolled in a prospective observational study between August 2016 and April 2020 in Botswana. Among all patients undergoing definitive chemoradiation, serum SCCAg was determined at pre-treatment baseline, end of treatment (EOT), and 3-month follow-up (normal reference range 0.3 -1.9 ng/ml). Normalization of SCCAg was defined as return to the reference range after treatment (SCCAg response), and was measured first at EOT; if EOT values were not available, 3-month values were utilized. Patients were staged according to FIGO 2009 criteria, early stage was defined as Stage I-II; while advanced stage was defined as Stage III-IV. Median follow-up was 44 months. A significant cut-off point for baseline and SCCAg response correlated with overall survival (OS) was calculated utilizing a log-rank test Among 234 patients who were diagnosed with histologically confirmed cervical cancer, 73.5% were WLWH (mean CD4 count 466 cells/mL). 92.9% of all cancers were squamous cell carcinoma. 68.8% of patients had elevated SCCAg at time of diagnosis. There was no significant difference in mean baseline SCCAg between WLWH (13.3 ng/mL) and women living without HIV (9.07 ng/mL), p = 0.1052. There was a significant difference seen in mean SCCAg between early (7.9 ng/mL ± SD 13.4) and advanced (18.9 ng/mL, ± SD 29.8) stage disease at diagnosis, p < 0.0001. Baseline SCCAg > 7.9 ng/mL was found to be associated with worse OS (p < 0.001). 5-year OS was significantly different among patients with SCCAg response < = 2.8 (5-year OS 66.2%), vs. SCCAg >2.8 ng/mL (5-year OS 42.4%). There was no significant difference in average SCCAg values between EOT (p = 0.68) and 3-month follow-up (p = 0.24). There was no difference in the proportion of patients who experienced normalized SCCAg by HIV status (p = 0.67). There was no significant difference in SCCAg among WLWH and women living without HIV. Among patients with elevated SCCAg above normal at baseline, SCCAg was associated with early vs. advanced stage disease. Additionally, there was a significant difference seen in overall survival by two measurement points: baseline SCCAg >7.9 ng/mL and response SCCAg >2.8 ng/mL. SCCAg may be utilized as a biomarker in low-resource settings to refine prognosis. Further studies will be needed to determine utility and validation in predicting recurrence risk and/or lymph node metastases. [ABSTRACT FROM AUTHOR]

Cervical cancer is the leading cause of cancer death among women in Botswana. It is well established that persistent human papillomavirus (HPV) infection is the primary risk factor for cervical cancer and that co-infection with human immunodeficiency virus (HIV) further increases the risk for cancer development. Standard of care for locally advanced disease is treatment with chemoradiation (CRT). This study aimed to characterize toxicities, response to treatment, and survival in patients with cervical cancer in Botswana. Patients with histologically confirmed locally advanced cervical cancer eligible for CRT were prospectively enrolled between Jan 2015 and June 2019 to the Ipabalele study in Gaborone, Botswana. Clinical and treatment characteristics, on-treatment toxicities, and treatment response of patients were recorded. Biochemical response to treatment was characterized using SCC-Ag level <2.2ng/ml at the end of treatment and 3 months post treatment. Toxicities were measured during on treatment visits (OTVs) and evaluated using CTCAE 4.0 grading. All patients were followed every 3 months for 2 years. Of 293 women diagnosed with cervical cancer, 73.7% (n=216) were women living with HIV (WLWH). The mean age of diagnosis for cervical cancer was younger in WLWH vs those without HIV (44.9 vs. 47.5, p<0.001). There was no difference in stage at presentation by HIV status, with the most common stage at presentation among both populations as Stage II (46.3% WLWH, 58.84% without HIV, p=0.349). Median CD4 count among WLWH was 467 cells/μL. WLWH had a lower external beam radiation dose (45.76 Gy) compared to women living without HIV (47.09 Gy), p=0.002; however, HIV status did not impact total EQD2 (median 85.7 Gy). HIV status did not impact number of chemotherapy cycles received (median 4 cycles). Seventy three percent (n=106) of all patients had a complete response to treatment by clinical exam and imaging, 65% (n=82) of all patients had a complete response to treatment by SCC-Ag. HIV status did not impact response to treatment by either SCC-Ag or clinical evidence (p=0.718). Two-year overall survival (OS) probability for the cohort was 77.7%. There was no difference in survival by HIV status (OS 75.8% in WLWH; 82.05% in those without HIV, p=0.31). Treatment response by SCC-Ag was associated with OS. Factors associated with OS in a multivariate analysis included cycles of chemotherapy given and stage at presentation. HIV was not significantly related to overall survival. The most common Grade2+ toxicities included anemia (42.8%, n=125), leukopenia (34.6%, n=101), and radiation dermatitis (39.9%, n=101). Importantly, HIV did not impact prevalence of any of the toxicities measured. HIV status impacted age of diagnosis of cervical cancer; however, did not impact stage, treatment received for cervical cancer, or OS. There was no difference seen in chemoradiation associated toxicities of treatment for locally advanced cervical cancer by HIV status. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Women living with HIV are at an increased risk of acquiring HPV-related cervical atypia that can progress to cervical cancer. In sub-Saharan Africa, cervical cancer makes up the largest proportion of years of life lost due to cancer, largely due to women diagnosed at younger ages, typically between 35 and 50 years. Botswana has the second highest prevalence of HIV in the world. Current World Health Organization guidelines for cervical cancer recommend screening between ages of 30-49 years; however, data suggest that women with HIV who get cervical cancer are diagnosed at a younger age. We assessed characteristics of women diagnosed with cervical cancer to further inform and refine screening guidelines.Materials/methods: 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 categorical age at diagnosis and HIV status, CD4 count, viral load and other sociodemographic and clinical factors.Results: Data were available for 1,130 women who were diagnosed with cervical cancer, 69.3% were women living with HIV (WLWH). Of the total 1130 women (median age 47.9 (IQR 41.2-59.1), 1.3 % were < 30 years of age, 19.1 % were 30-39 and 37.2% were 40-49. Overall, 20.4% (n = 231) of cancers were in women < 40 years. When analyzed by age, 86.7% of patients < 30 years of age were WLWH (mean CD4 371.6 cells/µL), 86.1% in patients 30-39 years (mean CD4 671.8 cells/µL). Overall, 86.1% of women who were < 40 years of age were WLWH compared to 64.9% of women who were ≥40 years old (P < 0.001). Mean CD4 counts for WLH who were < 40 years was 655.10 cells/µL and 18.2% had detectable viral load, while mean CD4 count for ≥40 years was 619.58 cells/µL with 23.8% having a detectable viral load. The most common FIGO stage of presentation in patients < 40 years was stage II (39.9%) compared to stage III (39.7%) in ≥40-year-old women (P = 0.08). Over three quarters (84.0%) of women < 40 years old were single compared to 60.8 % in those ≥40 years. Among women < 40 years old who were screened for cervical cancer, 87.4% (n = 111) were WLHV, and among women ≥40 years 70.5% (n = 308) were WLHV. Women < 40 years were more likely to have ever been screened than women ≥40 years old (59.1% vs 50.7%, P = 0.03).Conclusion: Age of cervical cancer diagnosis may be younger in countries with higher prevalence of HIV, like Botswana. Approximately 20% of the patients present with cancer < 40 years of age and should have been screened 10 years prior to cancer diagnosis to prevent cancer. However, these patients will not be screened per the current WHO screening guidelines. Changing international cervical cancer screening guidelines to women at younger ages than 30-49 years should be urgently considered especially in setting with high prevalence of HIV. Furthermore, engaging women without HIV in screening programs is critical for cervical cancer elimination. [ABSTRACT FROM AUTHOR]

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 < 0.01). We detected 66 LR-HPV subtypes among all cervical cancer patients, with HPV 6b and 48 being most prevalent. Notably, signatures for LR-HPV subtypes 10, 41, 90, and 129 were only detected in WLWH. Signal intensity for HPV 18 was significantly weaker in WLWH with CD4 levels ≤200 cells/μL as compared to patients with >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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: This study sought to compare the clinicopathologic features of women with breast cancer presenting in South Africa, Botswana, and the United States (US)., Methods: Breast cancer samples from Botswana (n = 384, 2011-2015), South Africa (n = 475, 2016-2017), and the US (n = 361,353, 2011-2012) were retrospectively reviewed., Results: The median age of sub-Saharan African women presenting with breast cancer (age 54 in Botswana and South Africa) was younger than that of those in the US (age 61) (P < 0.001). Sub-Saharan women were more likely to present with advanced stage disease than US counterparts (64.7% in Botswana, 63.3% in South Africa, 13% in the US, P < 0.001). Triple negative disease was highest in Botswana (21.3%) compared to South Africa (11.4%) and the US (12.94%) (P < 0.001). Differences in receptor status at presentation among the three cohorts (P < 0.001) were not observed when the cohorts were stratified by ethnicity. Black/multiracial patients in Botswana and the US were the most likely subsets to present with the adverse characteristic of triple negative disease (21.3% and 23.2%, respectively). No correlation was found between HIV and receptor status in the Botswana (P = 0.513) or South African (P = 0.352) cohorts., Conclusions: Here we report receptor status patterns at presentation in Botswana and South Africa. This study reveals important similarities and differences which may inform policy and provide context for future epidemiologic trends of breast cancer in low- and-middle-income countries particularly in sub-Saharan Africa., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© 2022. The Author(s).)

Background: In Botswana, nearly two-thirds of cervical cancer patients are HIV-positive. This study examined the relationship between CD4 count and chemoradiation therapy outcomes among cervical cancer patients with HIV., Setting: A prospective cohort study of 231 HIV-positive women with locally invasive cervical cancer was conducted in Gaborone, Botswana from January 2015 to February 2018., Methods: Primary outcome was survival, defined as time from scheduled end of chemoradiation therapy to death or last contact with patient. Nadir CD4 count was defined as lowest CD4 available before cancer diagnosis. Delta CD4 count was defined as improvement from nadir CD4 to CD4 at cancer diagnosis. Hazard ratio (HR) analyses were adjusted for presenting variables (age, baseline hemoglobin, cancer stage, and performance status) and treatment variables (chemotherapy cycles and radiation dose)., Results: Two hundred thirty-one patients were included in nadir CD4 analysis; 139 were included in delta CD4 analysis. Higher delta CD4 was significantly associated with reduced mortality after adjusting for presenting and treatment variables (CD4 100-249: HR 0.45, 95% CI: 0.21 to 0.95; CD4 ≥250: HR 0.45, 95% CI: 0.20 to 1.02). Higher nadir CD4 showed a trend toward reduced mortality after adjusting for presenting and treatment variables (HR 0.94, 95% CI: 0.84 to 1.06)., Conclusions: Higher delta CD4 (greater improvement from nadir CD4 to CD4 at cervical cancer diagnosis) is significantly associated with lower mortality. Although not statistically significant, data suggest that higher nadir CD4 may reduce mortality. These results reinforce the importance of early HIV diagnosis and antiretroviral therapy initiation, as their effects influence cervical cancer outcomes years later.

Background: The majority of new cancer cases are expected to be diagnosed in low- and middle-income countries (LMICs) by 2025, and 65% of cancer deaths currently occur in LMICs. Treatment adherence, patient monitoring, and follow-up are essential to cancer care but are often not possible in these settings. Out Patient (OP) Care, a smartphone application (app) developed to fill this gap, texts appointment reminders to patients and electronically stores medical records confidentially., Objectives: This study aims to present the development of this app and evaluate its usability and feasibility as defined by provider and patient experiences in the context of a multidisciplinary cancer clinic in Gaborone, Botswana., Methods: OP Care was piloted at a multidisciplinary team gynecologic oncology clinic in Gaborone, Botswana. The app was developed through an iterative process with feedback from clinic staff and physicians. The usability was evaluated using a cross-sectional survey. All staff members in the gynecologic oncology clinic, which typically consists of one doctor and four nurses, as well as a portion of the staff in the (Princess Marina Hospital general) oncology ward used the app. All providers using the app were surveyed, along with all patients who attended the gynecologic oncology clinic during the 3-week survey period. Staff demographics, reactions, and opinions on usability, as well as patients' reactions to the appointment reminders were collected. Agreement to the ease-of-usability statements was recorded on a 1 (not at all) to 7 (extremely so) scale. Primary outcomes were the app's usability and the feasibility of text reminders from the patient's perspective., Results: Nine staff and 15 patients were surveyed. Staff included three doctors and six nurses and encompassed all of the staff in the gynecologic oncology clinic as well as a portion of the general oncology ward. All surveyed staff owned a smartphone and used a computer at home. Most (78%) staff did not feel that OP Care would increase their work burden and were willing to use the app if implemented permanently (median: 6; interquartile range [IQR]: 1). Seventeen out of the nineteen usability questions, such as "I feel comfortable using this system," scored a median of 6, corresponding to "very much so." Patients reported that the reminder text messages were helpful (median: 6; IQR: 1) and preferred the text reminders to be in Setswana (median: 7; IQR: 1)., Conclusion: High usability scores indicate that the app can be scaled up to usage in this clinic and others. Although patients appreciate OP Care, the option for call and text reminders in Setswana is indicated., Competing Interests: Givy Dhaliwal is the CEO of ONE BCG, the company that developed the application that was implemented in this study. Sherman Preet Singh is also an employee of ONE BCG. This application was developed and is distributed at no cost to consumers, with only social goals in mind. The company gains no profit from this application., (Thieme. All rights reserved.)

Purpose: Botswana, a country with a high prevalence of HIV, has an increasing incidence of cancer-related mortality in the post-antiretroviral therapy era. Despite universal access to free health care, the majority of Botswana patients with cancer present at advanced stages. This study was designed to explore the factors related to advanced-stage cancer presentation in Botswana., Methods: Patients attending an oncology clinic between December 2015 and January 2017 at Princess Marina Hospital in Gaborone, Botswana, completed a questionnaire on sociodemographic and clinical factors as well as cancer-related fears, attitudes, beliefs, and stigma. Odds ratios (ORs) were calculated to identify factors significantly associated with advanced stage (stage III and IV) at diagnosis., Results: Of 214 patients, 18.7% were men and 81.3% were women. The median age at diagnosis was 46 years, with 71.9% of patients older than 40 years. The most commonly represented cancers included cervical (42.3%), breast (16%), and head and neck (15.5%). Cancer stages represented in the study group included 8.4% at stage I, 19.2% at stage II, 24.1% at stage III, 11.9% at stage IV, and 36.4% at an unknown stage. Patients who presented at advanced stages were significantly more likely to not be afraid of having cancer (OR, 3.48; P < .05), believe that their family would not care for them if they needed treatment (OR, 6.35; P = .05), and believe that they could not afford to develop cancer (OR, 2.73; P < .05). The perception that symptoms were less serious was also significantly related to advanced stage ( P < .05). Patients with non-female-specific cancers were more likely to present in advanced stages (OR, 5.67; P < .05)., Conclusion: Future cancer mortality reduction efforts should emphasize cancer symptom awareness and early detection through routine cancer screening, as well as increasing the acceptability of care-seeking, especially among male patients.

Purpose: To prospectively compare survival between human immunodeficiency virus (HIV)-infected versus HIV-uninfected cervical cancer patients who initiated curative chemoradiation therapy (CRT) in a limited-resource setting., Methods and Materials: Women with locally advanced cervical cancer with or without HIV infection initiating radical CRT in Botswana were enrolled in a prospective, observational, cohort study from July 2013 through January 2015., Results: Of 182 women treated for cervical cancer during the study period, 143 women initiating curative CRT were included in the study. Eighty-five percent of the participants (122 of 143) had stage II/III cervical cancer, and 67% (96 of 143) were HIV-infected. All HIV-infected patients were receiving antiretroviral therapy (ART) at the time of curative cervical cancer treatment initiation. We found no difference in toxicities between HIV-infected and HIV-uninfected women. The 2-year overall survival (OS) rates were 65% for HIV-infected women (95% confidence interval [CI] 54%-74%) and 66% for HIV-uninfected women (95% CI 49%-79%) (P = .70). Factors associated with better 2-year OS on multivariate analyses included baseline hemoglobin >10 g/dL (hazard ratio [HR] 0.37, 95% CI 0.19-0.72, P = .003), total radiation dose ≥75 Gy (HR 0.52, 95% CI 0.27-0.97, P = .04), and age <40 years versus 40-59 years (HR 2.17, 95% CI 1.05-4.47, P = .03)., Conclusions: Human immunodeficiency virus status had no effect on 2-year OS or on acute toxicities in women with well-managed HIV infection who initiated curative CRT in Botswana. In our cohort, we found that baseline hemoglobin levels, total radiation dose, and age were associated with survival, regardless of HIV status., (Copyright © 2018 Elsevier Inc. All rights reserved.)