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.

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.

Introduction: Cervical cancer, a malignancy caused by infection with oncogenic human papillomavirus, disproportionally affects women from low resource settings. Persistence of human papillomavirus infection may mediate an association between tobacco use and cervical cancer. In limited resource settings, women from indigenous communities are often marginalized and do not benefit from evidence-based interventions to prevent tobacco use or cervical cancer due to the limited reach of mainstream healthcare services to these communities. This study determined the association between smoking and high-risk human papillomavirus infection among women from indigenous communities in western Botswana. Methods: A cross-sectional study of women in indigenous communities was conducted between June and October 2022. Demographic, clinical and self-reported smoking data were collected. Cervical cytology and HPV DNA testing for high-risk human papillomavirus genotypes were performed. Multilevel multivariable logistic regression models were fit to evaluate the association between smoking and high-risk human papillomavirus infection while adjusting for potential confounders. Results: A total of 171 participants with a median (interquartile range) age of 40 (31–50) years from three settlements and two villages were recruited for the study. Of these, 17% were current smokers, 32.8% were living with HIV and high-risk human papillomavirus DNA was detected in 32.8% of the cervical specimens. Women who were current smokers, were nearly twice as likely to have cervical high-risk human papillomavirus infection compared to non-smokers (Adjusted Odds Ratio (95% CI); 1.74(1.09, 2.79)) after controlling for confounders. Conclusion: These data underscore the need for effective tobacco control to help mitigate cervical cancer risk in this setting. These findings can help inform decisions about targeted cervical cancer prevention and tobacco cessation interventions for women from indigenous communities.

Breast cancer remains the most diagnosed cancer among women world-wide and a leading cause of cancer-related deaths accounting for 15% of deaths in 2018. Worldwide, the incidence increased from 1.4 million in 2011 to over 2 million in 2018 with a concomitant increase in mortality from 458,400 to 626,679 in the same period. Low- and middle-income countries, such as Botswana, have a disproportionate burden of breast cancer incidence and mortality and there is an urgent need to characterise the unique tumour molecular profiles that may be influencing mortality in these populations. Methods A retrospective study of 125 archived mastectomy specimens (from 2006 to 2009) from women with breast cancer in Botswana was conducted. We determined molecular characteristics of breast cancers by carrying out four immunohistochemistry (IHC)classification (PR, ER, HER2 receptors and Ki 67), cytokeratin 5/6 and EGFR1.Statistical software STATA and SPSS were used to determine the relationship between histology, IHC of biomarkers of interest. Results Out of 125 breast cancer tissues, the distribution of molecular subtypes were as follows: Luminal A (44/125; 35.2%), Luminal B (and TNBC (23/125; 18,4%), HER2 Enriched (17/125; 13.6%), and Luminal B HER2 Enriched (9/125; 7.2%), Basal (9/125; 7.2%), and CK5/6 was expressed by 12.8% (16/125) of tumours. Furthermore 6% of the tumours were basal positive luminal tumours. Morphological 76% of tumours were IDC-NOS and 24% were special type, majority were grade 2 (40%) followed by grade 1(30.4%), grade 3 (23.2%) was and mucinous types were 6.4%. Clinical staging and tumour involvement data were incomplete. Conclusion The discovery of basal positive luminal breast tumours in women from Botswana original not accounted for in the four distinct molecular subtype calls for an expanded antibody panel 6-IHC panel) in order to stratify women of African descent patients into good/poor prognostic groups. Characterising tumour subtypes will better inform optimal therapeutic regimens for women with breast cancer in Botswana.

Background/Objective: High-risk human papillomavirus (hrHPV) is an established causative agent for the malignant transformation of cervical cells that can be detected using the Papanicolaou (Pap) smear test. A call by the World Health Organization (WHO) for global collective efforts towards eliminating cervical cancer has endorsed hrHPV DNA testing as an alternative screening test. The objective of this study was to determine the diagnostic utility of hrHPV DNA testing in detecting high-grade cervical intraepithelial lesions (HSILs) in unvaccinated women with abnormal Pap smears and histopathologically confirmed CIN3 and carcinoma. Methods: This study included 111 cervical tissues with a histopathological confirmation of the cervical intraepithelial neoplasia grade (CIN3) and malignancy. Tissues were sectioned, dewaxed, and digested, and DNA was extracted and tested for hrHPV using the Abbott RealTime HR HPV assay. Pap smear results associated with the tissue samples were extracted from corresponding clinical records, and data was analyzed using R-statistical software. Results: Extracted Pap smear records for the 111 cervical tissue samples indicated that 89 (80.2%) had a high-grade intraepithelial lesion (Pap-HSIL), 20 (18%) had squamous cell carcinoma (Pap-SCC), and two (1.8%) had Pap-adenocarcinoma. A total of 68/89 (76.4%) of Pap-HSIL, 15/20 (75%) of Pap-SCC, and ½ (50%) of Pap-adenocarcinoma cases had detectable hrHPV DNA. Conclusions: This study’s findings demonstrate that the Pap smear is still a valuable screening test especially for detecting both hrHPV-dependent and -independent cervical dysplasia in unvaccinated populations. While considerations are made to improve cervical cancer screening, including the introduction of hrHPV DNA testing in national cervical cancer screening programs, there is a need for the careful interpretation of molecular testing results for clinical intervention. This is especially important for hrHPV-independent cervical dysplasia screening, since this can have dire implications for clinically asymptomatic women.