Introduction: 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.

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.

PURPOSEIn Botswana, a see-and-treat approach to cervical cancer screening is taken. Our objective was to determine the number of loop electrosurgical excision procedures (LEEPs) performed for cervical intraepithelial neoplasia (CIN) 2/3 in Botswana, and follow-up rates and outcomes, among women with positive cervical margins.METHODSData (patient age, HIV status, margin status, follow-up, and recurrence) from women who underwent LEEP with histologically confirmed CIN 2/3 between January 2014 and December 2015 were analyzed retrospectively. Histopathologic reports were reviewed at a central laboratory in Gaborone, Botswana. Follow-up and recurrence rates were summarized descriptively and compared according to HIV and margin statuses using chi-squared tests.RESULTSIn total, 779 women (median age, 39.2 years) underwent LEEP showing CIN2/3; 638 (81.9%) women had CIN3 and 390 (50.1%) had positive LEEP margins (ectocervical, 186 [47.7%]; endocervical [including with ectocervical], 204 [52.4%]). Margin positivity was not associated with HIV status. Of women with positive endocervical margins followed at ≤1 and >1 year, 9.6% and 48.3%, respectively, had persistent CIN2/3 on repeat LEEP. Forty percent (90 of 204) of women with positive endocervical margins had no re-excision documented.CONCLUSIONMost women who underwent LEEP had CIN3 and positive margins. Almost half with positive margins followed at >1 year after initial LEEP had CIN2/3 recurrence warranting further treatment; two thirds were not followed. Resources are needed to improve post-LEEP follow-up for women with margin positivity who require additional ablative/excisional procedures to reduce the cervical cancer burden in Botswana.

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.

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.

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.

PURPOSEPatients 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).METHODSThis 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.RESULTSIn 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.CONCLUSIONPatients 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.

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.

Globally, the prevalence of noncommunicable diseases (NCDs), such as cancer and cardiovascular disease, is on the rise, placing burdens on economic growth and health systems in resource-limited settings. In sub-Saharan Africa, the situation is exacerbated by the increasing prevalence of HIV and the associated infectious diseases. In this article, we describe the impact of a Mentoring Core funded through a grant from the US National Cancer Institute of the National Institutes of Health (NIH) that focuses on North-South collaborations to build research capacity in Botswana, Africa, in topics related to HIV and cancer. We describe the goals of the mentoring program, two research projects awarded through pilot grant funding, and discuss how individual junior faculty members at the University of Botswana benefited from the mentorship and collaborations that helped them gain research skills in HIV and cancer.

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.

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.

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.