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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

Keneuoe Cecilia Nthontho,1,2 Andrew Khulekani Ndlovu,1 Kirthana Sharma,3 Ishmael Kasvosve,1 Daniel Louis Hertz,4 Giacomo Maria Paganotti2,5,6 1School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana; 2Botswana-University of Pennsylvania Partnership, Gaborone, Botswana; 3Rutgers Global Health Institute, New Brunswick, NJ, USA; 4Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA; 5Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 6Department of Biomedical Sciences, Faculty of Medicine, University of Botswana, Gaborone, BotswanaCorrespondence: Giacomo Maria Paganotti, Botswana-University of Pennsylvania Partnership, PO Box 45498, Riverwalk Gaborone, Botswana, Tel +267 3555375, Email paganottig@bup.org.bwAbstract: Breast cancer is the most frequent cause of cancer death in low- and middle-income countries, in particular among sub-Saharan African women, where response to available anticancer treatment therapy is often limited by the recurrent breast tumours and metastasis, ultimately resulting in decreased overall survival rate. This can also be attributed to African genomes that contain more variation than those from other parts of the world. The purpose of this review is to summarize published evidence on pharmacogenetic and pharmacokinetic aspects related to specific available treatments and the known genetic variabilities associated with metabolism and/or transport of breast cancer drugs, and treatment outcomes when possible. The emphasis is on the African genetic variation and focuses on the genes with the highest strength of evidence, with a close look on CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5, CYP19A1, UGT1A4, UGT2B7, UGT2B15, SLC22A16, SLC38A7, FcγR, DPYD, ABCB1, and SULT1A1, which are the genes known to play major roles in the metabolism and/or elimination of the respective anti-breast cancer drugs given to the patients. The genetic variability of their metabolism could be associated with different metabolic phenotypes that may cause reduced patients’ adherence because of toxicity or sub-therapeutic doses. Finally, this knowledge enhances possible personalized treatment approaches, with the possibility of improving survival outcomes in patients with breast cancer.Keywords: breast cancer, genetic variability, inter-ethnic differences, pharmacogenetics, sub-Saharan Africa, toxicity

Background: Cervical cancer remains a public health problem despite heavy global investment in health systems especially in low-and-middle-income countries (LMIC). Prophylactic vaccines against the most commonly detected human papillomavirus (HPV) types in cervical cancers are available and decisions on the selection of vaccine design depends on the prevalence of high-risk (hr) HPV genotypes for a particular region. In 2015, Botswana adopted the use of a quadrivalent HPV vaccine as a primary prevention strategy. Secondary prevention includes cervical smear screening whose uptake remains notably low among indigenous and marginalized communities despite efforts to improve access., Aim: To determine the prevalence of hrHPV genotypes and cervical lesions' burden in women from the indigenous and marginalized communities of Botswana., Methods: This prospective survey enrolled 171 non-HPV vaccinated women aged 21 years and older. Face-to-face interviews, Pap smear screening, hr-HPV and Human Immuno-deficiency virus (HIV) testing were carried out. Conventional Papanicolau smears were analyzed and cervical brushes were preserved for hrHPV testing using the Ampfire Multiplex HR-HPV protocol which detects the following genotypes: HPV 16, 18, 31, 35, 39, 45, 51, 52, 53, 56, 58, 59 and 68., Results: In this study, 168/171 (98.6%) of the women consented to HIV testing; 53/171 (31%) were living with HIV and self-reported enrolment on antiretroviral therapy. Among the women examined, 23/171 (13.5%) had cervical dysplasia with most presenting with Atypical Squamous Cells of Undetermined Significance 8/23 (35%), Low-Grade Squamous Intraepithelial Lesions 8/23 (35%), Atypical Squamous Cells-High Grade 4/23 (17%), Atypical Endocervical Cells 2/23 (9%) and Atypical Endocervical Cell favoring neoplasia 1/23(4%). However, no High-Grade Squamous Intraepithelial Lesions (HSIL) or squamous cell carcinoma (SCC) were detected. Overall hrHPV prevalence in this study was at 56/171 (32.7%). The most commonly detected hrHPV genotypes in women with cervical dysplasia were HPV39 (6.25%), HPV51 (14.5%), HPV52 (12.5%) and HPV56 (4%). Notably, HPV 16 and 18 were not found in women with cervical dysplasia., Conclusions: Our study provides valuable insights into the prevalence and distribution of hrHPV genotypes in indigenous and marginalized communities in Botswana, and the need for further investigation of their potential role in cervical carcinogenesis in this population. These results may also serve as baseline data to facilitate future evaluation of the HPV vaccine needs., (© 2024. The Author(s).)

Cervical cancer is the fourth most common malignancy in women of reproductive age globally. The burden of this disease is highest in low-income and middle-income countries, especially among women living with HIV. In 2018, WHO launched a global strategy to accelerate cervical cancer elimination through rapid scale-up of prophylactic vaccination, cervical screening, and treatment of precancers and cancers. This initiative was key in raising a call for action to address the stark global disparities in cervical cancer burden. However, achieving elimination of cervical cancer among women with HIV requires consideration of biological and social issues affecting this population. This Position Paper shows specific challenges and uncertainties on the way to cervical cancer elimination for women living with HIV and highlights the scarcity of evidence for the effect of interventions in this population. We argue that reaching equity of outcomes for women with HIV will require substantial advances in approaches to HPV vaccination and improved understanding of the long-term effectiveness of HPV vaccines in settings with high HIV burden cervical cancer, just as HIV, is affected by social and structural factors such as poverty, stigma, and gender discrimination, that place the elimination strategy at risk. Global efforts must, therefore, be galvanised to ensure women living with HIV have optimised interventions, given their substantial risk of this preventable malignancy., Competing Interests: Declaration of interests SMG is a recipient of funds from Merck educational grants; receives consulting fees from Merck as a member of the Global Advisory Board for HPV; and receives honoraria and travel support for meetings from Merck Sharp & Dohme. SMG holds an unpaid position as the President of the International Papillomavirus Society; is an honorary board member of the Asia Oceania Research Organization on Genital Infections and Neoplasia; and is also a co-Chair of the Asia Pacific HPV Coalition. AJV is a recipient of funding from the Global Alliance for Chronic Diseases (GNT2009196)/National Health & Medical Research Council Australia, Minderoo Foundation (PS64872), and the NHMRC (Leadership Investigator Grant GNT2007901); and reports donated goods and materials from Cepheid USA outside of the submitted work. HR is a member of the WHO Strategic Advisory Group of Experts HPV Working Group and co-Chair of the HPV Single Dose Vaccine Evaluation Consortium; and is Chair of the South African Health Products Regulatory Board. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)