Prevalence and Associated Factors of High-Risk Human Papillomavirus Infections among Human Immunodeficiency Virus-Infected Women in Lagos, Nigeria.

Background: Given the synergistic relationship between human immunodeficiency virus (HIV) and human papillomavirus (HPV) infections, knowledge of the genotypic prevalence and associated factors of high-risk HPV (HR-HPV) among HIV-infected women is crucial for developing targeted interventions such as appropriate screening tests and effective genotype-specific vaccination. Objectives: We determined the prevalence of any HR-HPV and multiple HR-HPV infections and identified associated factors among a cohort of women living with HIV infections (WLHIV) in Lagos, Nigeria. Methods: This descriptive cross-sectional study analysed the data of 516 WLHIV who underwent cervical cancer screening as part of the COMPASS-DUST study at the HIV treatment centre of Lagos University Teaching Hospital from July 2023 to March 2024. Multivariable binary logistic regression models were performed to explore factors associated with HR-HPV and multiple HR-HPV infections. Results: Among the 516 WLHIV enrolled (mean age, 46.5±7.3 years), the overall HR-HPV prevalence was 13.4% (95% CI, 10.6-16.6), disaggregated as 3.3% for HPV16/18 (95% CI, 1.9-5.2) and 11.6% for other HR-HPV genotypes (95% CI, 9.0-14.7). Nineteen women (3.7%; 95% CI, 2.2-5.7)had multiple HR-HPV genotype infections. Having a recent serum CD4+ cell count ≤560 cells/µL (adjusted OR 3.32; 95% CI 1.06-10.38) and HPV 16/18 genotype infections (adjusted OR 38.98; 95% CI 11.93-127.37) were independently associated with an increased risk of multiple HR-HPV infections. Conclusion: The findings of this study provide valuable insights into the epidemiology of HR-HPV infections and highlight the need for tailored interventions and continuous monitoring. By addressing these challenges through targeted screening, effective ART management, and vaccination programs, we can improve health outcomes and reduce the burden of cervical cancer in this vulnerable population.

Comparative Assessment of p16/Ki-67 Dual Staining Technology for cervical cancer screening in women living with HIV (COMPASS-DUST)-Study protocol.

The risk of progression of low-grade (CIN1) to high-grade cervical intraepithelial neoplasia (CIN2/3) is 3-5 times higher for women living with HIV (WLHIV) than for HIV-negative women. Evidence suggests that the current cervical cancer screening methods perform less effectively in WLHIV. An emerging screening method-p16/Ki-67 dual staining technology (DUST) is a safe and rapid assay that could be used to detect CIN2/3 with higher sensitivity and specificity. The study in this protocol will evaluate the performance of DUST in cervical cancer screening among WLHIV. We will conduct an intra-participant comparative study (Phase 1) to enrol n = 1,123 sexually active WLHIV aged 25-65 years at two accredited adult HIV treatment centres in Lagos, Nigeria to compare the performance of DUST to the currently used screening methods (Pap smear, hr-HPV DNA, or VIA testing) in detecting high-grade CIN and cancer (CIN2+). Subsequently, a prospective cohort study (Phase 2) will be conducted by enrolling all the WLHIV who are diagnosed as having low-grade CIN (CIN1) in Phase 1 for a 6-monthly follow-up for 2 years to detect the persistence and progression of CIN1 to CIN2+. The findings of this study may provide evidence of the existence of a better performance screening method for the primary and triage detection of CIN2+ in WLHIV. It may also demonstrate that this high-performance test can improve the long-term predictive accuracy of screening by extending the intervals between evaluations and thus decrease the overall cost and increase screening uptake and follow-up compliance in WLHIV.

Distribution of Cancer and Cancer Screening and Treatment Services in Lagos: A 10-Year Review of Hospital Records.

PURPOSE: In Lagos State, Nigeria, the population distribution of cancers is poorly described because studies are conducted at a few tertiary hospitals. Therefore, this study aims to map all health facilities where cancer screening takes place and describe the cases of cancer screened for and treated. METHODS: A cross-sectional survey to identify facilities involved in screening and management of cancers was performed followed by extraction of data on individual cases of cancer screened for and treated at these facilities from 2011 to 2020. All health care facilities in the state were visited, and the survey was performed using standardized national tools modified to capture additional information on cancer screening and treatment. Data analysis was performed using STATA version 14 and R version 3.6.3. RESULTS: Cervical cancer was the commonest cancer, accounting for 55% of 2,420 cancers screened, followed by breast (41%), prostate (4%), and colorectal cancers (0.2%). Of the 7,682 cancers treated among Lagos residents, the top five were breast (45%), colorectal (8%), cervical (8%), prostate (5%), and ovarian (4%). The female:male ratio of cancer cases was 3:1. The peak age for cancer among females and males was in the 40- to 49-year age group and 60- to 69-year age group, respectively. The Ikorodu local government area had the highest rate of reported cancer per million population. CONCLUSION: Cancer screening is poor with a significant gap in screening for breast cancer since it is the commonest cancer in the state. The findings indicate the urgent need for the establishment of organized screening programs for the predominant cancers in the state and the prioritization of cancer research that addresses key policy and program questions.

Analysis of the genomic landscapes of Barbadian and Nigerian women with triple negative breast cancer.

PURPOSE: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately affects women of African ancestry (WAA) and is often associated with poor survival. Although there is a high prevalence of TNBC across West Africa and in women of the African diaspora, there has been no comprehensive genomics study to investigate the mutational profile of ancestrally related women across the Caribbean and West Africa. METHODS: This multisite cross-sectional study used 31 formalin-fixed paraffin-embedded (FFPE) samples from Barbadian and Nigerian TNBC participants. High-resolution whole exome sequencing (WES) was performed on the Barbadian and Nigerian TNBC samples to identify their mutational profiles and comparisons were made to African American, European American and Asian American sequencing data obtained from The Cancer Genome Atlas (TCGA). Whole exome sequencing was conducted on tumors with an average of 382 × coverage and 4335 × coverage for pooled germline non-tumor samples. RESULTS: Variants detected at high frequency in our WAA cohorts were found in the following genes NBPF12, PLIN4, TP53 and BRCA1. In the TCGA TNBC cases, these genes had a lower mutation rate, except for TP53 (32% in our cohort; 63% in TCGA-African American; 67% in TCGA-European American; 63% in TCGA-Asian). For all altered genes, there were no differences in frequency of mutations between WAA TNBC groups including the TCGA-African American cohort. For copy number variants, high frequency alterations were observed in PIK3CA, TP53, FGFR2 and HIF1AN genes. CONCLUSION: This study provides novel insights into the underlying genomic alterations in WAA TNBC samples and shines light on the importance of inclusion of under-represented populations in cancer genomics and biomarker studies.

Primary vaginal leiomyosarcoma: case report of a rare gynaecological malignancy and diagnostic challenge in a resource-constraint setting.

Primary vaginal leiomyosarcoma (VLMS) is an extremely rare variant of primary vaginal cancers with very poor prognosis irrespective of the stage at presentation and the type of treatment received. It is easily recurrent and has a high propensity for haematogenous spread especially to the lungs. We present the case of a 34-year-old Para 1 + 1 (1 alive) woman with recurrent vaginal mass of 8 years duration after two surgical excisions without histological evaluation. She had examination under anaesthesia and a wide local excision of the vaginal mass. Histological examination of the mass revealed poorly differentiated VLMS with positive surgical margins and she was commenced on adjuvant chemo-radiation. Histological evaluation remains the hallmark for diagnosing rare malignancies like VLMS, which unfortunately is not a standard practice in some resource-constraint settings.

Evaluating Barriers and Opportunities in Delivering High-Quality Oncology Care in a Resource-Limited Setting Using a Comprehensive Needs Assessment Tool.

PURPOSE: Despite recognition of both the growing cancer burden in low- and middle-income countries and the disproportionately high mortality rates in these settings, delivery of high-quality cancer care remains a challenge. The disparities in cancer care outcomes for many geographic regions result from barriers that are likely complex and understudied. This study describes the development and use of a streamlined needs assessment questionnaire (NAQ) to understand the barriers to providing quality cancer care, identifies areas for improvement, and formulates recommendations for implementation. METHODS: Using a comprehensive NAQ, in-depth interviews were conducted with 17 hospital staff involved in cancer care at two teaching hospitals in Nigeria. Data were analyzed using content analysis and organized into a framework with preset codes and emergent codes, where applicable. RESULTS: Data from the interviews were organized into six broad themes: staff, stuff, system, space, lack of palliative care, and provider bias, with key barriers within themes including: financial, infrastructural, lack of awareness, limited human capacity resources, lack of palliative care, and provider perspective on patient-related barriers to cancer care. Specific solutions based on ability to reasonably implement were subcategorized into short-, medium-, and long-term goals. CONCLUSION: This study provides a framework for a streamlined initial needs assessment and a unique discussion on the barriers to high-quality oncology care that are prevalent in resource-constrained settings. We report the feasibility of collecting and organizing data using a streamlined NAQ and provide a thorough and in-depth understanding of the challenges in this setting. Knowledge gained from the assessments will inform steps to improve oncology cancer in these settings.

Kaiso is highly expressed in TNBC tissues of women of African ancestry compared to Caucasian women.

PURPOSE: Triple-negative breast cancer (TNBC) is most prevalent in young women of African ancestry (WAA) compared to women of other ethnicities. Recent studies found a correlation between high expression of the transcription factor Kaiso, TNBC aggressiveness, and ethnicity. However, little is known about Kaiso expression and localization patterns in TNBC tissues of WAA. Herein, we analyze Kaiso expression patterns in TNBC tissues of African (Nigerian), Caribbean (Barbados), African American (AA), and Caucasian American (CA) women. METHODS: Formalin-fixed and paraffin embedded (FFPE) TNBC tissue blocks from Nigeria and Barbados were utilized to construct a Nigerian/Barbadian tissue microarray (NB-TMA). This NB-TMA and a commercially available TMA comprising AA and CA TNBC tissues (AA-CA-YTMA) were subjected to immunohistochemistry to assess Kaiso expression and subcellular localization patterns, and correlate Kaiso expression with TNBC clinical features. RESULTS: Nigerian and Barbadian women in our study were diagnosed with TNBC at a younger age than AA and CA women. Nuclear and cytoplasmic Kaiso expression was observed in all tissues analyzed. Analysis of Kaiso expression in the NB-TMA and AA-CA-YTMA revealed that nuclear Kaiso H scores were significantly higher in Nigerian, Barbadian, and AA women compared with CA women. However, there was no statistically significant difference in nuclear Kaiso expression between Nigerian versus Barbadian women, or Barbadian versus AA women. CONCLUSIONS: High levels of nuclear Kaiso expression were detected in patients with a higher degree of African heritage compared to their Caucasian counterparts, suggesting a role for Kaiso in TNBC racial disparity.

Clinicopathological and molecular characteristics of Ku 70/80 expression in Nigerian breast cancer and its potential therapeutic implications.

Ku 70/80 is a regulator of the Non-Homologous End Joining (NHEJ) roles in clinicopathological features, and has prognostic significance in breast cancer (BC) in Caucasian populations. However, its significance in the Nigerian BC population, which is characterized by a higher rate of the triple-negative and basal phenotype, p53 mutation rate and BRCA1 deficiency, still needs to be investigated. We hypothesize that Ku70/80 expression shows adverse expression in Nigerian BC and, furthermore, that it is likely to have a therapeutic implication for Black BC management. This study investigated the biological, clinicopathological and prognostic significance of Ku 70/80 expression in a BC cohort from a Nigerian population. Ku 70/80 expression was determined in 188 well-characterized formalin-fixed, paraffin-embedded (FFPE) BC samples using tissue microarray and immunohistochemistry. Ku 70/80 expression was correlated with clinicopathological, molecular and prognostic characteristics of patients. Ku 70/80 was expressed in 113 (60.1%) tumors, and was positively associated with metastatic disease, triple-negative and basal phenotype, BRCA1 down regulators (MTA-1 and ID4), p-cadherin, PI3KCA and p53 expression. It inversely correlated with BRCA1, BRCA2, BARD1 and p27. Ku 70/80 was predictive of breast cancer-specific survival in multivariate analysis, but not of disease-free interval. This study demonstrated that Ku 70/80 expression is associated with triple negativity and down-regulation of the homologous recombination pathway of DNA repair. Therefore, the development of novel drugs to target KU70/80 may improve the patients' outcome in the treatment of Black BC.

Expression of the SIBLINGs and their MMP partners in human benign and malignant prostate neoplasms.

The small integrin binding ligands n-linked glycoproteins (SIBLINGs) have emerged as potential diagnostic and prognostic indices, and as key targets, in cancer therapy. Three members of the SIBLING family: bone sialoprotein (BSP); osteopontin (OPN); and dentin matrix protein1 (DMP1), bind and interact with specific matrix metalloproteinases (MMPs): BSP-MMP2; OPN-MMP3; DMP1-MMP9, in biochemical and biologic systems. The other two family members are dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). The specific SIBLING-MMP pairing reported in some cancers have not been reported in prostate neoplasms. In this study, we investigated SIBLING-MMP expression and potential interaction in prostate neoplasms. Chi square analysis of immunohistochemistry results showed significant upregulation of OPN (X2=25.710/p<0.001), BSP (X2=19.546/p<0.001), and DSPP (X2=8.720/p=0.003) in prostate adenocarcinoma (pAdC). MEPE was significantly upregulated in benign prostate hyperplasia (BPH; X2=44.153/p<0.001). There were no significant differences in MMP expression between BPH and pAdC. Western blot analysis showed significantly elevated BSP and DSPP in prostate cancer-derived cells. Immunofluorescence studies confirmed BSP-MMP2, OPN-MMP3, and DMP1-MMP9 coexpression in two cancer-derived cell lines, whereas in situ proximity ligation assays confirmed potential BSP-MMP2, OPN-MMP3, and DMP1-MMP9 interactions in BPH and pAdC. Our reports provide evidence that SIBLING-MMP interaction may play a role in the progression of BPH to pAdC.

Breast Cancer Reporting in Lagos, Nigeria: Implications for Training and Education in Africa.

PURPOSE: To assess the completeness and accuracy of breast cancer pathologic reporting in Nigeria. MATERIALS AND METHODS: The histologic parameters provided in breast cancer pathology reports at a large teaching hospital in Nigeria were assessed. The corresponding slides were reviewed after the United Kingdom Royal College of Pathologists guidelines, and results were compared. RESULTS: Out of 115 breast cancer cases, histologic type of breast carcinoma was concordant with the review type in 53.1% of cases and discordant in 46.9%. Grading was stated in 89.62% of cases, of which 50.5% were correctly graded, 35.8% were under-graded, and 8.5% were over-graded. Poor fixation and omission of the mitotic count were the main reasons for discordant grades. A comment on lymph node status was included in 40% of cases, and lymphovascular invasion was not commented on in 97.4% of cases. Only 26% of the tumors had hormone receptors and/or HER2 tested. CONCLUSION: Some essential histologic parameters were absent from the histologic reports, and where present, a proportion were inaccurate. Attention to specimen fixation and method of grading and familiarity with uncommon breast cancer types are required; all can be facilitated by education and training. The use of a template/proforma is recommended to ensure cancer data set parameters are included in the pathology reports.

Molecular profiling of breast cancer in Nigerian women identifies an altered p53 pathway as a major mechanism underlying its poor prognosis compared with British counterpart.

BACKGROUND: Advances in breast cancer (BC) research have demonstrated differences between black and white women with regarding tumour behaviour, patient outcome and response to treatment which can be explained by underlying genetic changes. The tumour suppressor gene p53 has been speculated to be involved in tumour biology of triple negative and/or basal -like BC and more commonly observed in black than caucasian women. MATERIALS AND METHODS: In this study, the protein expression of p53 was investigated in tissue samples from a series of 308 Nigerian women, prepared as a tissue microarray (TMA), using immunohistochemistry. Clinicopathological parameters, biomarkers of functional significance in BC and patient outcome of tumours expressing p53 in Nigerian women were correlated with UK grade matched series. RESULTS: A significantly large proportion of BC from Nigerian women showed high p53 expression compared with UK women (p<0.001). In those tumours showing positive p53 in the Nigerian series, a significant proportion were premenopausal, diagnosed before 50 years, larger in size, with evidence of metastasis into lymphatic vessels ( all p<0.001). In addition, p53 positive expression was also significantly correlated with negative expression of ER and PgR (p<0.001, p<0.03 respectively), BRCA1, MDM2 (all p<0.001), p21 (p=0.006) and E-cadherin (p=0.001) and positively associated with P-cadherin (p=0.001), triple negative phenotype, basal cytokeratin (CK) 5/6 expression (p<0.04) and basal phenotype compared with the UK series (p<0.001). Survival analyses showed Nigerian women with BC were significantly associated with poor BC specific survival (p<0.001, but no significant association with disease free interval was observed. CONCLUSION: In this study, protein expressions of p53 pathways are different between Nigerian and UK BC women and this may also contribute to differences in tumour biology. Therefore, targeting these p53 pathways for therapeutic usage might improve the poor outcome observed in Black Nigerian women.

Histopathological patterns of ovarian tumours seen in Lagos University Teaching Hospital: a ten year retrospective study.

BACKGROUND: Among gynaecological cancers, ovarian malignancy is the most lethal, largely due to the fact that it is not diagnosed until late stage. Information concerning the frequency and pattern of ovarian tumours in Lagos is scant. OBJECTIVE: To present a 10 year retrospective histologic study of ovarian tumours in Lagos, Nigeria. The aim is to document the histologic pattern, prevalence and age distribution of ovarian tumours. METHOD: The materials consisted slides, paraffin embedded tissue blocks, patients' case files and histology request forms of all ovarian biopsies received at the Morbid Anatomy department of Lagos University Teaching Hospital Idi-Araba, Lagos from 1991 to 2000. RESULTS: A total of 486 ovarian biopsies were studied out of which 203 specimens were true ovarian neoplasms. One hundred and sixty three (80.3%) of the true neoplasms were benign while malignant ovarian tumours constituted 40 (19.7%). Ovarian malignancy constituted about 7% of 203 gynaecological malignant tumours in the 10 year period under review. Tumours of germ cell origin were the commonest, accounting for 107 (52.7%) of the true ovarian neoplasm seen. Surface epithelial tumours constituted 56 (27.6%), while sex cord-stromal tumours contributed 32 (15.8%). Mature teratoma was the commonest benign tumour, accounting for 98 (60.1%) cases of benign ovarian tumours. It showed a wide age range of occurrence, with peak occurrence between 20 and 29 years. Serous cystadenocarcinoma (42.5%) was the commonest ovarian malignancy. Serous cystadenocarcinoma occurred between the ages of 20 and 69 years with highest frequency in 30-39 years age group, CONCLUSION: The germ cell tumours were the commonest ovarian neoplasm followed by surface epithelial tumours. This pattern is seen in most parts of Nigeria and Africa.