Women of sub-Saharan African descent have disproportionately higher incidence of Triple Negative Breast Cancer (TNBC), and TNBC-specific mortality. Population comparative studies show racial differences in TNBC biology, including higher prevalence of basal-like and Quadruple-Negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily United States (US) populations. Due to heterogenous genetic admixture, and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNAseq on an international cohort of AAs, west and east Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed tumor-associated immunological profiles are distinct in patients of African descent.

Background. Human papilloma virus (HPV) is involved in the development of cancer of the cervix, mouth and throat, anus, penis, vulva, or vagina, but it has not been much considered as a cause of breast cancer. Recently, a number of investigations have linked breast cancer to viral infections. High-risk HPV types, predominantly HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59, are established as carcinogens in humans. In this study we aimed to detect 19 high-risk and 9 low-risk HPVs from archived breast tumor tissue among Ethiopian women. Methods. In this study, 75 breast cancer patients from Tikur Anbassa Specialized Hospital in Addis Ababa (Ethiopia) were included. HPV detection and genotyping were done using the novel Anyplex™ II HPV28 Detection Assay at the Orebro University Hospital, Sweden. The Anyplex™ II PCR System detects 19 high-risk HPV types (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 69, 73, and 82) and 9 low-risk HPV types (6, 11, 40, 42, 43, 44, 54, 61, and 70). IHC for p16 was done using an automated system, the Dako Autostainer Link. Results. Out of the 75 valid tests, two were found to be positive (2.7%) for HPV. One of the cases was positive for the high-risk HPV16 genotype while the other was positive both for the high-risk HPV39 and the low-risk HPV6. The cell cycle protein p16 was highly expressed in the case positive for the high-risk HPV16, but it was not expressed in the case positive for HPV39. Conclusion. The prevalence of HPV is low in Ethiopian breast cancer patients, but the role played by HPV in breast carcinogenesis among Ethiopian breast cancer patients cannot be commented based on these observations.

Summary: In order to accurately detect and prevent racial disparities, self-reported race (SRR) and ethnicity remain valuable tools; however, inaccurate capture of patient identity and broad aggregation of minoritized race groups present challenges for data interpretation. Also, although SRR is a proxy for shared social/cultural experience, it is not an accurate representation of shared endogenous factors. Biological investigations into cancer disparities, particularly those involving genetic features, should be framed in the context of genetic background or ancestry, as these are heritable aspects of population health. In reality, both genetics and environment work in concert to influence cancer risk and clinical outcomes. The best opportunity to define actionable means for reducing health disparities is in rigorous and comprehensive generation of rich data sets that characterize environmental, biological, and genetic components of disparate disease burden. To translate this pivotal disparities research into clinical tools and improved policies, we describe a diversity, equity, inclusion, and accessibility (DEIA) framework, which will increase participation from diverse backgrounds, reexamine previous research with a rigorous evaluation of appropriate SRR groupings, and engage community leaders to ensure that future research addresses the needs of communities at increased risk. On this path forward, we may finally end cancer disparities.

Background: Triple-negative breast cancer (TNBC) remains the most aggressive molecular subtype of breast cancer, with worse survival outcomes compared to other breast cancer subtypes. TNBC prevalence is highest among women of African descent worldwide, and through our previous work we have established a connection between West African ancestry (WAa) and higher rates of TNBC. Specifically, we have shown that prevalence rates of TNBC among West African and African American women are similar and higher than that of East African and White American women. We have also shown that quantified African ancestry is higher among TNBC cases compared to non-TNBC cases. To determine the influence African ancestry on the TNBC tumor environment, we sought to determine any differences in gene expression profiles of Ghanaian (West African) compared to Ethiopian (East African) women. Methods: RNA was extracted and sequenced from a pilot cohort of archival FFPE tumor tissue among Ghanaian (n = 19) and Ethiopian (n = 20) women. RNAseq reads were aligned, and quality of alignments were assessed, where de-duplicated samples with counts above 10M reads were included in the final analysis. Genetic ancestry was quantified by obtaining SNVs called from the RNAseq alignments, using GATK best practices. Differentially expressed genes lists were determined comparing Ghanaian vs. Ethiopian TNBC tumors, and also by identifying genes that were associated with increasing African ancestry. These gene lists, and log-fold change between comparison groups, were used as input for Ingenuity Pathway Analysis (IPA), to identify canonical pathways and de novo networks that are specific to Ghanaian or Ethiopian TNBC tumors. Results: Using 1KG populations as our reference to quantify genetic ancestry, we show that Ghanaian samples have >94% AFR ancestry, specifically matching population groups representative of WAa. The Ethiopian samples showed between 37-48% AFR ancestry, primarily represented by East African groups. Interestingly, there seems to be a significant proportion of EUR ancestry among the Ethiopians samples (30-49%), primarily represented by Italian ancestry. We have conducted the differential gene expression analysis in two ways. First, we have compared gene expression profiles between Ghanaian and Ethiopian tumors. In our preliminary analysis, we identified >600 genes (p < 0.01) that were differentially expressed between Ghanaian and Ethiopian TNBC tumors. Second, we used AFR ancestry as a continuous variable, where we conducted a linear regression analysis to identify genes associated with AFR ancestry. We identified >900 genes associated with AFR ancestry (p < 0.01), and this gene signature distinguished Ghanaian from Ethiopian tumors in an unsupervised hierarchical clustering. In comparing the differentially expressed gene lists from these two approaches, approximately 200 genes were shared, indicating the distinct value of both analyses. Using these gene lists as input for IPA analysis, we have begun to identify canonical pathways that have been altered by our differentially expressed genes, alongside de novo networks that differ between our Ghanaian and Ethiopian tumors. In our overlapping gene list, we see predicted differences in functions such as quantity of T lymphocytes, where genes downregulated in Ethiopian tumors may indicated reduced presence of these immune cells. Using CIBERSORT and xCell deconvolution methods, validation of these findings are ongoing. Conclusions and Ongoing work: This work highlights how ancestry-specific gene regulation can delineate differences in the tumor microenvironment among a cohort of African tumors. We are currently evaluating distribution of TNBC subtypes and estimation of immune cell populations in these tumors, to determine ancestry-specific differences in tumor heterogeneity and immune response. Citation Format: Rachel Martini, Endale Gebregzabher, Princesca Dorsaint, Timothy Chu, Kanika Arora, Lee Gibbs, Zarko Manojlovic, Nicolas Robine, Andrea Sboner, Olivier Elemento, John Carpten, Lisa Newman, Melissa Davis. Gene expression profiles of Ghanaian and Ethiopian triple-negative breast tumors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SS1-07.

Background: HPV have been implicated in the development of cancer of the cervix, mouth and throat, anus, penis, vulva, or vagina, but it has not been much considered as a cause of breast cancer. However, a growing number of investigations have linked breast cancer to viral infections. High-risk HPV types, predominantly (HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, and -59) are established as carcinogens in humans, while HPV-68 is probably carcinogenic. In this study we aimed to detect 19 high risk and 9 low risk HPVs from archived breast tumor tissue among Ethiopian women.Methods: In this study, 75 breast cancer patients from Tikur Anbassa Specialized Hospital in Addis Ababa (Ethiopia) were included. HPV detection and genotyping were done using the novel Anyplex™ II HPV-28 Detection Assay at the Orebro University Hospital, Sweden. The AnyplexTMII PCR System detects 19 high-risk HPV types (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 69, 73, 82) and 9 low-risk HPV types(6, 11, 40, 42, 43, 44, 54, 61, 70). IHC for p16 was done in automated system using the Dako Autostainer Link.Results: Out of the 75 valid tests 2 were found to be positive (2.7%) for HPV. One of the cases were positive for high risk HPV16 genotype while the other were positive both for high risk HPV39 and low risk HPV6. The cell cycle protein p16 was highly expressed in the case positive for the high risk HPV16 but it was not expressed in the case positive for HPV39.Conclusion: With limited number of cases positive for HPV in this study, it is our conclusion that cervical cancer prevention strategies may help protection of breast cancer only in small groups of patients. Due to limitation of the number of participants in the study as well as possible other mechanisms of carcinogenesis, our observation should be reconfirmed using a larger set of patients and in case-control design.

Background Continuing professional development (CPD) is required for health workers in practice to update knowledge and skills regularly to match the changing complexity of healthcare needs. The objective of this study was to identify the training needs of Medical Laboratory professionals in Ethiopia. Methods A total of 457 medical laboratory professionals from five regions and two city administrations were involved in the study. Data were collected from August 02 to 21, 2021 with structured self-administered online tool with five-point Likert scale. The tool had consent, demography, cross-cutting issues, and main activity area specific to medical laboratory. Results Majority of the participants were male (80.1%). Participants from Amhara region 110 (24.1%) were the largest groups in the survey followed by Oromia 105 (23%) and Addis Ababa 101 (22.1%). The study participants comprised 54.7% with a bachelor’s degree, 31.3% with a diploma (associate degree), and 14% with a master’s degree. The participants had varying years of service, ranging from less than one year to over 10 years of experience. Most of the participants work as generalists (24.1%) followed by working in microbiology (17.5%) and parasitology (16%). The majority (96.9%) were working in a public sector or training institutions and the rest were employed in the private sector. Our study showed that the three most important topics selected for training in the cross-cutting health issues were health and emerging technology, computer skills and medico-legal issues. Topics under microbiology, clinical chemistry and molecular diagnostics were selected as the most preferred technical areas for training. Participants have also selected priority topics under research skill and pathophysiology. When the laboratory specific issues were regrouped based on areas of application as technical competence, research skill and pathophysiology, thirteen topics under technical competence, four topics under research skill and three topics under pathophysiology were picked as priority areas. Conclusion In conclusion, our study identified that CPD programs should focus on topics that address technical competence in microbiology, clinical chemistry and molecular diagnostics. Additionally competencies in research skill and updating knowledge in pathophysiology should also receive due attention in designing trainings.

Introduction/Objective Continuing professional development (CPD) is required for health workers in practice to update knowledge and skills regularly to match the changing complexity of healthcare needs. The objective of this study was to identify the training needs of Medical Laboratory professionals in Ethiopia. Methods/Case Report A total of 457 Medical Laboratory professionals from five region and two city administrations were involved in the study. Data was collected from August 02 to 21, 2021 with structured self-administered online tool with five-point Likert scale. The tool had consent, demography, cross-cutting issues, and main activity area specific to medical laboratory. Results (if a Case Study enter NA) Majority of the participants were male (80.1%). Participants from Amhara region 110 (24.1%) were the largest groups in the survey followed by Oromia 105(23%) and Addis Ababa 101(22.1%). The study participants comprised of 54.7% with a Bachelor degree, 31.3% with a diploma (Associate degree), and 14% with a Master’s degree. The participants had varying years of service, ranging from less than one year to over 10 years of experience. Most of the participants work as generalists (24.1%) followed by working in microbiology (17.5%) and Parasitology (16%). The majority (96.9%) was working in a public sector or training institutions and the rest were employed in the private sector. Our study showed that the three most important topics selected for training in the cross cutting health issues were health and emerging technology, computer skills and medico-legal issues. Topics under microbiology, clinical chemistry and molecular diagnostics were selected as the most preferred technical areas for training. Participants have also selected topics under research skill and pathophysiology. When the laboratory specific issues were regrouped based on areas of application as technical competence, research skill and pathophysiology, thirteen topics under technical competence, four topics under research skill and three topics under pathophysiology were picked as priority areas. Conclusion In conclusion, our study identified that CPD programs should focus on topics that address technical competence in microbiology, clinical chemistry and molecular diagnostics. Additionally competencies in research skill and updating knowledge in pathophysiology should also receive due attention in designing trainings.

Women of sub-Saharan African ancestry have disproportionately higher incidence of aggressive, early-onset Triple Negative Breast Cancer (TNBC), and TNBC mortality across all race groups. Population-based comparative studies show racial differences in TNBC tumor biology, with higher prevalence of basal-like and Quadruple-Negative subtypes in African Americans (AA). However, most investigations relied on self-reported race (SRR) of primarily United States (US) populations. However, given that genetic admixture in AAs is extremely heterogenous, and race-correlated social determinants can translate into biological differences, the true association of African ancestry with TNBC biology and gene expression is currently unclear. To address this, we conducted RNAseq on an international cohort of AAs, west and east Africans with TNBC. Using genetic ancestry estimation in this African-enriched cohort, we identified 613 genes associated with African ancestry and more than 2200 genes associated with regional-level African ancestry. Functional enrichment and deconvolution revealed tumor-associated immune cell infiltration and activity.