Search

Pleasure Ramatlho,1,2 Moses Muganyizi Rugemalila,3 Leabaneng Tawe,1,2 Debanjan Pain,4,5 Ontlametse T Choga,1,6 Andrew Khulekani Ndlovu,1 Moses O Koobotse,1 Priti Lal,5 Timothy R Rebbeck,7,8 Giacomo M Paganotti,2,9 Mohan Narasimhamurthy,5 Lynnette Tumwine Kyokunda3 1School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana; 2Botswana-University of Pennsylvania Partnership, Gaborone, Botswana; 3Department of Pathology, Faculty of Medicine, University of Botswana, Gaborone, Botswana; 4Department of Medicine (Hematology-Oncology), University of Pennsylvania, Philadelphia, PA, USA; 5Hospital of University of Pennsylvania, Philadelphia, PA, USA; 6Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; 7Division of Population Science, Dana-Farber Cancer Institute, Boston, MA, USA; 8Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; 9Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USACorrespondence: Pleasure Ramatlho, Pleasure Ramatlho School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana, Tel +26777572242, Email pleasureram@gmail.comIntroduction: Prostate cancer (CaP) is the most common malignancy and the second leading cause of cancer-related deaths among men in Botswana. Currently, diagnosing CaP relies on examining prostate biopsy samples, which can be challenging due to benign mimics. This study aims to evaluate the potential of Alpha-methyl acyl-CoA racemase (AMACR/p504s) and p63, as diagnostic markers for CaP. This may potentially validate the use of immunohistochemistry for detecting CaP in Botswana, where it is not routinely utilized.Methods: The study included 69 samples, comprising 5 prostatic chip specimens, 50 core biopsies, and 14 radical prostatectomy specimens. These cases were reviewed and categorized into CaP (49 cases) and benign prostatic hyperplasia (BPH) (20 cases). Immunohistochemistry was performed using AMACR/p504s and p63 immunohistochemical stains.Results: The study found that AMACR/p504s had a sensitivity of 96% and a specificity of 95%, while p63 had a sensitivity and specificity of 100%. PSA levels showed significant positive correlation with AMACR/p504s expression (P < 0.00001).Discussion: In this study, we have demonstrated the diagnostic utility of AMACR/p504s and p63 due to their high sensitivity and specificity in detecting CaP in Botswana, where these biomarkers are not yet widely used. Furthermore, utilizing these markers in conjunction with other diagnostic tools, such as PSA levels and morphological evaluation, could improve the diagnostic accuracy, especially in challenging cases where histopathological examination alone may be inconclusive.Keywords: prostate cancer, AMACR/p504s, p63, benign prostatic hyperplasia, Botswana

In recent years, the synchronous occurrence of tumors of different histotypes arising in the same organ has been reported more frequently in the literature. In the stomach, adenocarcinoma has been described with coexisting primary rhabdomyosarcoma, carcinoid, and low-grade B-cell lymphoma of mucosa-associated lymphoid tissue. The simultaneous development of adenocarcinoma and gastric mesenchymal tumor has been documented rarely. We report one such case. A 65-year-old male was diagnosed with a proximal gastric adenocarcinoma and underwent subtotal gastrectomy. Subsequent histopathological examination revealed the presence of another tumor at the gastric antrum. This was a gastrointestinal stromal tumor of low risk category (GIST). The literature has only a few previous reports of this very rare association. It is not known whether this synchronicity is incidental or there is a causative factor inducing the development of tumors of different histotypes in the same organ. Pathologists, oncologists and surgeons should be aware of this interesting condition.

We present one of the largest cohorts of TP53-pathogenic germline variants (PGVs) associated with patients with Li-Fraumeni syndrome (n = 82) with breast tumors (19 to 76 y; median age: 35). Most had missense variants (77%), followed by large gene rearrangements (LGRs; 12%), truncating (6%), and splice-site (5%) variants. Twenty-one unique germline missense variants were found, with hotspots at codons 175, 181, 245, 248, 273, 334, and 337. Of 100 total breast tumors, 63% were invasive (mostly ductal), 30% pure ductal carcinoma in situ, 4% fibroepithelial lesions, and 3% with unknown histology. Unlike BRCA-associated tumors, approximately half of the breast cancers exhibited HER2-positivity, of which ~50% showed estrogen receptor coexpression. Pathology slides were available for review for 61 tumors (44 patients), and no significant correlation between the type of TP53 PGVs and histologic features was noted. High p53 immunohistochemistry expression (>50%) was seen in 67% of tumors tested (mostly missense variant). Null pattern (<1% cells) was seen in 2 (LGR and splicing variants carriers). Surprisingly, 2 tumors from patients with an LGR and 1 tumor from a patient with a truncating variant showed p53 overexpression (>50%). The subset of patients with the Brazilian p.R337H variant presented at a higher age than those with non-p.R337H variant (46 vs 35 y) though statistically insignificant (P = 0.071) due to an imbalance in the sample size, and were uniquely negative for HER2-overexpressing tumors. To conclude, breast cancer in carriers of TP53 PGVs has some unique clinicopathological features that suggest differential mechanisms of tumor formation. p53 immunohistochemistry cannot be used as a surrogate marker to identify germline TP53-mutated breast cancers., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Pathogenic germline TP53 alterations cause Li-Fraumeni Syndrome (LFS), and breast cancer is the most common cancer in LFS females. We performed first of its kind multimodal analysis of LFS breast cancer (LFS-BC) compared to sporadic premenopausal BC. Nearly all LFS-BC underwent biallelic loss of TP53 with no recurrent oncogenic variants except ERBB2 (HER2) amplification. Compared to sporadic BC, in situ and invasive LFS-BC exhibited a high burden of short amplified aneuploid segments (SAAS). Pro-apoptotic p53 target genes BAX and TP53I3 failed to be up-regulated in LFS-BC as was seen in sporadic BC compared to normal breast tissue. LFS-BC had lower CD8+ T-cell infiltration compared to sporadic BC yet higher levels of proliferating cytotoxic T-cells. Within LFS-BC, progression from in situ to invasive BC was marked by an increase in chromosomal instability with a decrease in proliferating cytotoxic T-cells. Our study uncovers critical events in mutant p53-driven tumorigenesis in breast tissue., Competing Interests: NB, RM, RH, HD, AL, MG, GK, AR, MT, MLR and KNM report no conflicts of interest. KAS reports fees for consultant services, advisor or speaker from Clinica Alemana Santiago, Shattuck Labs, AstraZeneca, Takeda, Torque/Repertoire Therapeutics, CSRlife, Agenus, Genmab, Sanofi, Parthenon Therapeutics, Bristol-Myers Squibb, Roche, Molecular Templates, Merck, PeerView, PER and Forefront Collaborative. KAS reports research funding from Tesaro/GSK, Moderna Inc., Takeda, Surface Oncology, Merck, Bristol-Myers Squibb, AstraZeneca, Ribon Therapeutics, Eli Lilly, Boehringer-Ingelheim, Roche and Akoya Biosciences. AJL is founder and shareholder of PMV Pharma, a biotech company that works on reactivator of mutant p53. B.G. has received honoraria for speaking engagements from Merck, Bristol Meyers Squibb, and Chugai Pharmaceuticals; has received research funding from Bristol Meyers Squibb and Merck; and has been a compensated consultant for Darwin Health, Merck, PMV Pharma, Shennon Biotechnologies, and ROME Therapeutics of which he is a co-founder.

Myofibroblastoma is a rare benign mesenchymal tumor first described in the breast. It is also known as mammary-type myofibroblastoma outside of the breast, more frequently located along the embryonic milk line. Exceptionally, myofibroblastoma can occur at visceral locations. We present a case of myofibroblastoma detected incidentally in the liver. A well-circumscribed mass, grossly measuring 6.2 cm in the liver parenchyma, was found on imaging studies. Histologically, the lesion is characterized by benign spindle cells in a hyalinized collagenous stroma, with positive staining for SMA and ER, focal positivity for CD34, negative for desmin, and loss of RB1. This rare tumor at such an unusual location makes it diagnostically challenging, especially on core biopsy of the lesion. To our knowledge, this is the second case of myofibroblastoma in the liver reported in the English literature and the first such case with a detailed pathology description., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Nepal has a high burden of cervical cancer primarily due to a limited screening program. Most present with advanced cervical disease. Despite no national cervical cancer control program, Nepal's Ministry of Health and Population has taken many initiatives with various international collaborations in screening, vaccination, and treating pre-invasive and invasive cancer. However, the existing prevention and treatment modalities are dismally inadequate to meet the targets of WHO's cervical cancer eliminative initiative by 2030. We provide an overview of the Ministry of Health and Population, Nepal's efforts to tackle the growing cervical cancer burden in the country. We discuss the challenges and potential solutions that could be practical and augment screening uptakes, such as single-dose vaccination and HPV DNA tests. The screen-and-treat approach on the same day could potentially address treatment delays and follow-up loss after testing positive. Our narrative summary highlights existing and innovative strategies, unmet needs, and collaborations required to achieve elimination across implementation contexts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Narasimhamurthy and Kafle.)

Purpose: Patients who are HIV-positive and have breast cancer have worse overall survival (OS) compared with patients who are HIV-negative. Pathologic complete response (pCR) and relative dose intensity (RDI) of chemotherapy are associated with survival. We assessed whether pCR and RDI rates were lower for patients who are HIV-positive and received neoadjuvant chemotherapy (NACT)., Methods: This was a prospective cohort analysis of patients initiating NACT in Botswana (February 2017 to September 2019). Primary outcomes were pCR and RDI; secondary outcomes were OS and toxicity. HIV status and zidovudine (ZDV) treatment were stratification factors. Multivariable analysis was used to control for confounding., Results: In total, 26 of 110 enrolled individuals were HIV-positive. In univariable analysis, HIV-positive (odds ratio [OR] = 0.2; P = .048) and RDI < 0.85 (OR = 0.30; P = .025) were associated with pCR. In multivariable analysis, the magnitude of association decreased for HIV-positive (OR = 0.28; P = .11), but RDI < 0.85 remained independently associated with pCR (OR = 0.32; P = .035). Patients who are HIV-positive had significantly lower mean RDI, and those on ZDV had significantly lower RDI. Ninety-one (83%) were stage III with 2-year OS significantly worse for patients who are HIV-positive (58% v 74%). Hazard ratio for all-cause mortality was 2.68 (95% CI, 1.17 to 6.13; P = .028) in patients who are HIV-positive compared with patients who are HIV-negative. Toxicity rates were similar despite patients who are HIV-positive receiving significantly lower dose intensity chemotherapy., Conclusion: Patients who are HIV-positive and have breast cancer in Botswana have lower pCR rates and also receive lower dose intensity therapy, which may contribute to worse OS. Patients who are HIV-positive on ZDV-containing regimens received even lower dose intensity of NACT. Administering optimal dose intensity in patients who are HIV-positive remains a challenge, and targeted interventions that address modifiable risk factors are needed to improve therapy delivery and outcomes., Competing Interests: Robert GrossConsulting or Advisory Role: PfizerResearch Funding: Merck (Inst) Lawrence N. ShulmanResearch Funding: Celgene (Inst), Independence Blue Cross (Inst) Surbhi GroverHonoraria: Varian Medical SystemsConsulting or Advisory Role: GenesisCareResearch Funding: Varian Medical Systems Angela DeMicheleResearch Funding: Pfizer (Inst), Genentech (Inst), Calithera Biosciences (Inst), Novartis (Inst)No other potential conflicts of interest were reported.

Background: Epidemics of human immunodeficiency virus (HIV) and cervical cancer are interconnected. DNA hypermethylation of host genes' promoter in cervical lesions has also been recognized as a contributor to cervical cancer progression. Methods: For this purpose we analyzed promoter methylation of four tumor suppressor genes ( RARB, CADM1, DAPK1 and PAX1 ) and explored their possible association with cervical cancer in Botswana among women of known HIV status. Overall, 228 cervical specimens (128 cervical cancers and 100 non-cancer subjects) were used. Yates-corrected chi-square test and Fisher's exact test were used to explore the association of promoter methylation for each host gene and cancer status. Subsequently, a logistic regression analysis was performed to find which factors, HIV status, high risk-HPV genotypes, patient's age and promoter methylation, were associated with the following dependent variables: cancer status, cervical cancer stage and promoter methylation rate. Results: In patients with cervical cancer the rate of promoter methylation observed was greater than 64% in all the genes studied. Analysis also showed a higher risk of cervical cancer according to the increased number of methylated promoter genes (OR = 6.20; 95% CI: 3.66-10.51; P < 0.001). RARB methylation showed the strongest association with cervical cancer compared to other genes (OR = 15.25; 95% CI: 6.06-40.0; P < 0.001). Cervical cancer and promoter methylation of RARB and DAPK1 genes were associated with increasing age (OR = 1.12; 95% CI: 1.01-1.26; P = 0.037 and OR = 1.05; 95% CI: 1.00-1.10; P = 0.040). The presence of epigenetic changes at those genes appeared to be independent of HIV status among subjects with cervical cancer. Moreover, we found that cervical cancer stage was influenced by RARB (χ 2 = 7.32; P = 0.002) and CADM1 (χ 2 =12.68; P = 0.013) hypermethylation, and HIV status (χ 2 = 19.93; P = 0.001). Conclusion: This study confirms the association between invasive cervical cancer and promoter gene methylation of tumor suppressing genes at the site of cancer. HIV infection did not show any association to methylation changes in this group of cervical cancer patients from Botswana. Further studies are needed to better understand the role of HIV in methylation of host genes among cancer subjects leading to cervical cancer progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tawe, Grover, Zetola, Robertson, Gaseitsiwe, Moyo, Kasvosve, Paganotti and Narasimhamurthy.)

Cervical cancer remains a significant cause of morbidity and mortality in women worldwide and is the leading cause of cancer-related death in Botswana. It is well established that women with HIV have a higher risk of persistent HPV infection leading to cervical cancer. We assessed HPV prevalence and genotype distribution in 126 tissue specimens from confirmed invasive cervical cancer cases using Abbott real-time PCR assay. Overall, 88 (69.8%) women were HIV-infected. Fifty-seven (64.8%) of the HIV-infected women had a baseline CD4 + count ≥350 cells/μl, and 82 (93.2%) were on antiretroviral therapy at the time of cervical cancer diagnosis. The median age of HIV-infected patients was significantly younger than that of HIV-uninfected patients (p < 0.001). HPV DNA was detected in all of 126 (100%) of tissues analyzed in our study. The HPV genotypes identified included the HPV-16 (75.4%), HPV-18 (28.6%) and other high-risk (hr) HPV genotypes (16.7%). HIV infection was positively associated with the presence of the HPV-16 genotype (p = 0.036), but not with HPV-18 or with other high-risk (hr)-HPV genotypes. Thirty-three percent of the patients had multiple hr-HPV genotypes, with higher rates in HIV-infected women. These results highlight the importance and potential impact of large-scale HPV vaccination programs covering HPV-16 and HPV-18 genotypes in countries like Botswana with high burden of HIV infection., (© 2019 UICC.)

Purpose: Kaposi sarcoma (KS) is an HIV-associated skin cancer that is highly prevalent in Botswana and associated with significant morbidity and mortality. Histopathology-confirmed diagnosis is required for chemotherapeutic interventions in Botswana, which creates barriers to care because of limited biopsy and pathology services. We sought to understand the role a dermatology specialist can play in improving KS care through quality improvement (QI) initiatives to reduce histologic turnaround times (TATs) for KS., Methods: Employment of a dermatology specialist within a public health care system that previously lacked a local dermatologist generated quality improvements in KS care. Retrospective review identified patients diagnosed with KS by skin biopsy in the predermatology QI interval (January 1, 2015, to December 31, 2015) versus the postdermatology QI interval (January 1, 2016, to November 31, 2017). Histology TATs and clinical characteristics were recorded. A t test compared the median histology TATs in the pre- and post-QI intervals., Results: A total of 192 cases of KS were diagnosed by skin biopsy. Nearly all (98.4%) were HIV-positive; and 52.8% of patients were male with a median age of 39 years. Median TAT in the postdermatology QI interval was 11 days (interquartile range, 12-23 days) compared with 32 days in the predermatology QI interval (interquartile range, 24-56 days; P < .00)., Conclusion: Dermatology-led QI initiatives to improve multispecialty care coordination can significantly decrease histology TATs for KS. The reduction of diagnostic delays is a key first step to decreasing the morbidity and mortality associated with this cancer in resource-limited settings.

Background: To characterize the clinico-pathological features including estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu (HER2) expression in breast cancers in Botswana, and to compare them by HIV status., Methods: This was a retrospective study using data from the National Health Laboratory and Diagnofirm Medical Laboratory in Gaborone from January 1, 2011 to December 31, 2015. Clinico-pathological details of patients were abstracted from electronic medical records., Results: A total of 384 unique breast cancer reports met our inclusion criteria. Of the patients with known HIV status, 42.7% (50/117) were HIV-infected. Median age at the time of breast cancer diagnosis was 54 years (IQR 44-66 years). HIV-infected individuals were more likely to be diagnosed before age 50 years compared to HIV-uninfected individuals (68.2% vs 23.8%, p  < 0.001). The majority of patients (68.6%, 35/51) presented with stage III at diagnosis. Stage IV disease was not presented because of the lack of data in pathology records surveyed, and additionally these patients may not present to clinic if the disease is advanced. Overall, 68.9% (151/219) of tumors were ER+ or PR+ and 16.0% (35/219) were HER2+. ER+ or PR+ or both, and HER2- was the most prevalent profile (62.6%, 132/211), followed by triple negative (ER-/PR-/HER2-, 21.3%, 45/211), ER+ or PR+ or both, and HER2+, (9.0%, 19/211) and ER-/PR-/HER2+ (7.1%, 15/211). There was no significant difference in receptor status noted between HIV-infected and HIV-uninfected individuals., Conclusions: Majority of breast cancer patients in Botswana present with advanced disease (stage III) at diagnosis and hormone receptor positive disease. HIV-infected breast cancer patients tended to present at a younger age compared to HIV-uninfected patients. HIV status does not appear to be associated with the distribution of receptor status in breast cancers in Botswana., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

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: Quality pathology is critical for timely diagnosis and management of breast cancer. Few studies have analyzed pathology turnaround time (TAT) in sub-Saharan Africa. The purpose of this study was to quantify TAT for breast cancer specimens processed by the National Health Laboratory and Diagnofirm Laboratory in Gaborone, Botswana, and additionally compare TAT before and after 2012 to evaluate the effect of pathology scale-up interventions by the Ministry of Health and Wellness., Methods: Retrospective analyses of TAT were performed for breast specimens submitted to the two laboratories from 2011 to 2015. TAT was calculated as the time from specimen collection and receipt in the laboratory to the date of final report sign-out. Descriptive statistics and rank sum test were used to compare temporal trends in TAT before and after 2012., Results: A total of 158 breast biopsy, 219 surgical, and 218 immunohistochemistry (IHC) specimens were analyzed. The median TAT in 2015 was 6 and 7 days for biopsy and IHC specimens, respectively, and 57.5 days for surgical specimens. There was a significant decrease in median TAT for biopsy specimens from 21.5 days in 2011 to 2012 compared with 8 days in 2013 to 2015 ( P < .001). There was also a significant decrease in median TAT for IHC specimens during the same period ( P < .001). However, there was no significant decline in median TAT for surgical specimens., Conclusion: The scale-up of pathology personnel and infrastructure by the Ministry of Health and Wellness significantly reduced median TAT for biopsy and IHC specimens. TAT for surgical specimens remains suboptimal. Efforts are currently under way to decrease TAT for surgical specimens to 7 days.

Introduction: The number and lifespan of individuals living with HIV have increased significantly with the scale-up of antiretroviral therapy. Furthermore, the incidence of breast cancer in women with HIV is growing, especially in sub-Saharan Africa (SSA). However, the association between HIV infection and breast cancer is not well understood., Methods: A literature search was performed to identify articles published in journals pertaining to breast cancer and HIV, with an emphasis on SSA. Selected US-based studies were also identified for comparison., Results: Among the 56 studies reviewed, the largest study examined 314 patients with breast cancer and HIV in the United States. There is no consensus on whether HIV infection acts as a pro-oncogenic or antioncogenic factor in breast cancer, and it may have no relation to breast cancer. A higher incidence of breast cancer is reported in high-income countries than in SSA, although breast cancer in SSA presents at a younger age and at a more advanced stage. Some studies show that patients with breast cancer and HIV experience worse chemotherapy toxicity than do patients without HIV. Data on treatment outcomes are limited. The largest study showed worse treatment outcomes in patients with HIV, compared with their counterparts without HIV., Conclusion: HIV infection has not been associated with different clinical presentation of breast cancer. However, some evidence suggests that concurrent diagnosis of HIV with breast cancer is associated with increased therapy-related toxicity and worse outcomes. Systematic prospective studies are needed to establish whether there is a specific association between breast cancer and HIV.

Purpose Delays in diagnosis and treatment of cancers can lead to poor survival. These delays represent a multifaceted problem attributable to patient, provider, and systemic factors. We aim to quantify intervals from symptom onset to treatment start among patients with cancer in Botswana and to understand potential risk factors for delay. Patients and Methods From December 2015 to January 2017, we surveyed patients seen in an oncology clinic in Botswana. We calculated proportions of patients who experienced delays in appraisal (between detecting symptoms and perceiving a reason to discuss them with provider, defined as > 1 month), help seeking (between discussing symptoms and first consultation with provider, defined as > 1 month), diagnosis (between first consultation and receiving a diagnosis, defined as > 3 months), and treatment (between diagnosis and starting treatment, defined as > 3 months). Results Among 214 patients with cancer who completed the survey, median age at diagnosis was 46 years, and the most common cancer was cancer of the cervix (42.2%). Eighty-one percent of patients were women, 60.7% were HIV infected, and 56.6% presented with advanced cancer (stage III or IV). Twenty-six percent of patients experienced delays in appraisal, 35.5% experienced delays help seeking, 63.1% experienced delays in diagnosis, and 50.4% experienced delays in treatment. Patient income, education, and age were not associated with delays. In univariable analysis, patients living with larger families were less likely to experience a help-seeking delay (odds ratio [OR], 0.31; P = .03), women and patients with perceived very serious symptoms were less likely to experience an appraisal delay (OR, 0.45; P = .032 and OR, 0.14; P = .02, respectively). Conclusion Nearly all patients surveyed experienced a delay in obtaining cancer care. In a setting where care is provided without charge, cancer type and male sex were more important predictors of delays than socioeconomic factors.

Archived Formalin-Fixed Paraffin-Embedded (FFPE) tissue specimens can be a valuable source of human papillomavirus (HPV) nucleic acids for molecular biological analyses in retrospective studies. Although successful amplification with polymerase chain reaction (PCR) is essential for analysis of HPV DNA extracted from cervical FFPE specimens, extensive DNA damage due to cross-linking and fragmentation results in poor yield. Therefore, techniques to improve the diagnostic rate and sensitivity from FFPE tissues through PCR is highly desired and of wider interest. To overcome this, a highly sensitive double-nested PCR methodology was designed and optimized for limited-resource laboratories coupled with an organic extraction of DNA. This method allows the detection of a broad range of HPV genotypes and also allowing the sequencing of the final amplicon. Validation of the new approach developed was done with an automated DNA extraction coupled with Real Time PCR. Results showed that the proposed method achieves 96.3% of HPV detection as compared to 100% Abbott m2000rt used as 'gold standard'. Moreover, the concordance rate between the two methods was equal for detecting HPV - 16 or - 18 genotypes. Nevertheless, the newly introduced assay has an advantage of: •Simultaneously identifying broad range of HPV genotypes besides HPV- 16 and - 18 from clinical samples.•It is an easy and cost-effective method that can be beneficial in resource-limited setting and can be employed for various molecular applications.•The method is indicated for highly degraded FFPE samples.

Introduction: Health system delays in diagnosis of cancer contribute to the glaring disparities in cancer mortality between high-income countries and low- and middle-income countries. In Botswana, approximately 70% of cancers are diagnosed at late stage and median time from first health facility visit for cancer-related symptoms to specialty cancer care was 160 days (IQR 59-653). We describe the implementation and early outcomes of training targeting primary care providers, which is a part of a multi-component implementation study in Kweneng-East district aiming to enhance timely diagnosis of cancers., Methods: Health-care providers from all public facilities within the district were invited to participate in an 8-h intensive short-course program developed by a multidisciplinary team and adapted to the Botswana health system context. Participants' performance was assessed using a 25-multiple choice question tool, with pre- and post-assessments paired by anonymous identifier. Statistical analysis with Wilcoxon signed-rank test to compare performance at the two time points across eight sub-domains (pathophysiology, epidemiology, social context, symptoms, evaluation, treatment, documentation, follow-up). Linear regression and negative binomial modeling were used to determine change in performance. Participants' satisfaction with the program was measured on a separate survey using a 5-point Likert scale., Results: 176 participants attended the training over 5 days in April 2016. Pooled linear regression controlling for test version showed an overall performance increase of 16.8% after participation (95% CI 15.2-18.4). Statistically significant improvement was observed for seven out of eight subdomains on test A and all eight subdomains on test B. Overall, 71 (40.3%) trainees achieved a score greater than 70% on the pretest, and 161 (91.5%) did so on the posttest. Participants reported a high degree of satisfaction with the training program's content and its relevance to their daily work., Conclusion: We describe a successfully implemented primary health care provider-focused training component of an innovative intervention aiming to reduce health systems delays in cancer diagnosis in sub-Saharan Africa. The training achieved district-wide participation, and improvement in the knowledge of primary health-care providers in this setting., Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02752061.

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.)

Purpose: Cervical cancer is a major cause of mortality in low- and middle-income countries (LMICs) and the most common cancer diagnosed in women in Botswana. Most women present with locally advanced disease, requiring chemotherapy and radiation. Care co-ordination requires input from a multidisciplinary team (MDT) to deliver appropriate, timely treatment. However, there are limited published examples of MDT implementation in LMICs., Methods: In May 2015, a weekly MDT clinic for gynecologic cancer care was initiated at Botswana's national referral facility. The MDT clinic served as a forum for discussion and coordination of patients with gynecologic cancer and consisted of a gynecologist, pathologist, medical oncologist, radiation oncologist, palliative care specialist, and nurse coordinator., Results: Between May 2015 and December 2015, 135 patients were seen in the MDT clinic. The mean age of the patients was 49 years. Most (60%) of the patients were HIV positive. The most common diagnosis was cervical cancer (60%), followed by high-grade cervical intraepithelial neoplastic lesions (12%) and vulvar cancer (11%). Only data up to September 2015 were assessed for treatment delays. It was found that only 38% of patients needed more than one visit for care coordination before treatment initiation. Among patients with cervical cancer, the median delay from date of biopsy to start of radiation treatment was 39 days (interquartile range, 34 to 57 days) for patients treated after MDT initiation, compared with 108 days (interquartile range, 71 to 147 days) for patients treated before MDT initiation ( P < .001)., Conclusion: Implementation of MDT clinics in LMICs is feasible and can help reduce delays in treatment initiation, as demonstrated by a gynecologic MDT clinic in Botswana. Streamlining care through MDT clinics can enhance care coordination and improve clinical outcomes. This model can apply to cancer care in other LMICs., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc. Surbhi GroverNo relationship to discloseSebathu Philip ChiyapoNo relationship to disclosePriya PuriNo relationship to discloseMohan NarasimhamurthyNo relationship to discloseBabe Eunice GaolebaleNo relationship to discloseNeo TapelaNo relationship to discloseDoreen Ramogola-MasireNo relationship to discloseMukendi K.A. KayembeNo relationship to discloseThabo MoloiNo relationship to disclosePonatshego Andrew GaolebaleNo relationship to disclose

Background: Kidney donor outcomes are gaining attention, particularly as donor eligibility criteria continue to expand. Kidney size, a useful predictor of recipient kidney function, also likely correlates with donor outcomes. Although donor evaluation includes donor kidney size measurements, the association between kidney size and outcomes are poorly defined., Methods: We examined the relationship between kidney size (body surface area-adjusted total volume, cortical volume and length) and renal outcomes (post-operative recovery and longer-term kidney function) among 85 kidney donors using general linear models and time-to-chronic kidney disease data., Results: Donors with the largest adjusted cortical volume were more likely to achieve an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m 2 over a median 24-month follow-up than those with smaller cortical volumes (P <0.001), had a shorter duration of renal recovery (1.3-2.2 versus 32.5 days) and started with a higher eGFR at pre-donation (107-110 versus 91 mL/min/1.73 m 2 ) and immediately post-nephrectomy (∼63 versus 50-51 mL/min/1.73 m 2 ). Similar findings were seen with adjusted total volume and length., Conclusions: Larger kidney donors were more likely to achieve an eGFR ≥60 mL/min/1.73 m 2 with renal recovery over a shorter duration due to higher pre-donation and initial post-nephrectomy eGFRs.

Cervical cancer is the leading cause of cancer-related mortality in the developing world, where HIV and Mycobacterium tuberculosis (TB) infection are also endemic. HIV infection is independently associated with increased morbidity and mortality among women with cervical cancer. TB is believed to increase the risk of malignancies and could cause chronic inflammation in the gynecologic tract. However, the relationship between cervical cancer and TB in settings hyperendemic for HIV is unknown. We found that 18 (10%) of a cohort of 180 women with cervical cancer in Botswana had a history of TB disease. Age and HIV infection were also associated with a history of TB disease. Our data show that prior TB disease is highly prevalent among patients with cervical cancer infected with HIV. The coexistence of cervical cancer, HIV infection, and prior TB infection might be higher than expected in the general population. Prospective studies are needed to better determine the impact of the collision of these three world health epidemics., Competing Interests: Authors’ disclosures of potential conflicts of interest and contributions are found at the end of this article. The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Nicola M. ZetolaNo relationship to discloseSurbhi GroverNo relationship to discloseChawangwa ModongoNo relationship to discloseSebathu P. ChiyapoNo relationship to discloseMemory Nsingo-BvochoraSpeakers' Bureau: AstraZeneca Travel, Accommodations, Expenses: Roche, AstraZenecaMohan NarasimhamurthyNo relationship to discloseLilie L. LinSpeakers' Bureau: Varian Medical Systems Research Funding: Varian Medical SystemsJoseph JarvisResearch Funding: Gilead SciencesSanghyuk S. ShinEmployment: Beckman CoulterErle RobertsonNo relationship to disclose

Objective: The microbiology and epidemiology of UTI pathogens are largely unknown in Botswana, a high prevalence HIV setting. Using laboratory data from the largest referral hospital and a private hospital, we describe the major pathogens causing UTI and their antimicrobial resistance patterns., Methods: This retrospective study examined antimicrobial susceptibility data for urine samples collected at Princess Marina Hospital (PMH), Bokamoso Private Hospital (BPH), or one of their affiliated outpatient clinics. A urine sample was included in our dataset if it demonstrated pure growth of a single organism and accompanying antimicrobial susceptibility and subject demographic data were available., Results: A total of 744 samples were included. Greater than 10% resistance was observed for amoxicillin, co-trimoxazole, amoxicillin-clavulanate, and ciprofloxacin. Resistance of E. coli isolates to ampicillin and co-trimoxazole was greater than 60% in all settings. HIV status did not significantly impact the microbiology of UTIs, but did impact antimicrobial resistance to co-trimoxazole., Conclusions: Data suggests that antimicrobial resistance has already emerged to most oral antibiotics, making empiric management of outpatient UTIs challenging. Ampicillin, co-trimoxazole, and ciprofloxacin should not be used as empiric treatment for UTI in this context. Nitrofurantoin could be used for simple cystitis; aminoglycosides for uncomplicated UTI in inpatients.