Association between Serum Folate and Vaginal High-Risk Human Papillomavirus Infections in United States Women.

BACKGROUND: Serum concentration of folate was inversely associated with cervical intraepithelial neoplasia and cervical cancer in some studies. The association between folate and human papillomavirus (HPV) infection, a necessary cause of cervical cancer, has not been well elucidated. OBJECTIVES: We evaluated whether serum folate concentrations were associated with high-risk HPV (hrHPV) infection. METHODS: The study population was 11,801 females, aged 18-59 y, enrolled in the National Health and Nutrition Examination Survey (NHANES), from 2003 to 2016, in the United States. In this cross-sectional study, prevalence ratios (PRs) of vaginal hrHPV were calculated using logistic regression models, by quintiles of serum folate. RESULTS: Females in the lowest quintile had <21.3 nmol/L of folate. Approximately 23% of the females (2733/11,801) were hrHPV positive. In age-adjusted models, folate was significantly associated with hrHPV infection. The PRs and 95% confidence intervals (CIs) were (PR: 1.52; 95% CI: 1.37, 1.70) for the first, (PR: 1.29; 95% CI: 1.15, 1.44) for the second, (PR: 1.19; 95% CI: 1.06, 1.34) for the third, and (PR: 1.09; 95% CI: 0.96, 1.23) for the fourth quintiles, compared with the females in the highest quintile, with a significant P value for trend, <0.0001. The association remained statistically significant after the models were further adjusted for lifestyle and sexual risk factors for hrHPV infection; the females in the lowest quintile were more likely to have hrHPV infection than those in the highest quintile (PR: 1.40; 95% CI: 1.11, 1.53). CONCLUSIONS: Results from this sample of females in the United States suggest that serum folate concentration is inversely associated with hrHPV infection.

Prevalence of vaginal HPV infection among adolescent and early adult girls in Jos, North-Central Nigeria.

PURPOSE: Knowledge of the prevalence of HPV infection among adolescent and early adult girls is essential to determining the best age for the introduction of HPV vaccine, monitoring vaccine efficacy, and giving insight into determinants of persistent high-risk HPV infection, a necessary cause of cervical cancer. Yet, there have been limited studies of HPV infection among adolescent and early adult girls in low-and-middle-income countries. METHODS: In this cross-sectional study, we randomly selected 205 girls, aged 9-20 years, from 10 schools in central Nigeria. We obtained informed consent and assent, collected data, and trained participants to self-collect vaginal samples using swab stick. We genotyped HPV using SPF10-DEIA/LiPA25 and analyzed data using Stata 14®. RESULTS: The mean (SD) age of the girls was 14.9 (2.3) years. We found HPV in 13.2% of vaginal swabs. The earliest age at which anyHPV and hrHPV infections were detected was 10 and 12 years respectively. The prevalence of any HPV peaked at 16 and 17 years, hrHPV at 16 years, lrHPV at 17 and 18 years and multiple hrHPV 18 years of age. The prevalence of hrHPV infection was 1.5% among the 9-12 years age group, 2.9% among 13-16 years and 3.4% among 17-20 years old. The commonest hrHPV types detected were 52 (3.9%), 18 (1.5%) and 51 (2.4%). The most common lrHPV types was 6 (2.9%). CONCLUSION: The prevalence of HPV infection in these urbanized young girls in Nigeria is high and commences after 9 years of age. HPV vaccination in this population should start at 9 years of age or younger to prevent the establishment of persistent HPV infection.

Genome-wide association study of prevalent and persistent cervical high-risk human papillomavirus (HPV) infection.

BACKGROUND: Genetic factors may influence the susceptibility to high-risk (hr) human papillomavirus (HPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence. METHODS: Participants were 517 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF10/LiPA25. hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done for hrHPV infection (125 cases/392 controls) and for persistent hrHPV infection (51 cases/355 controls) under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes. RESULTS: The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. No single variant reached genome-wide significance (p < 5 X 10- 8). The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p = 1.43 × 10- 6). The top variants associated with cervical hrHPV persistence were in DAP (OR: 6.86, p = 7.15 × 10- 8), NR5A2 (OR: 3.65, p = 2.03 × 10- 7) and MIR365-2 (OR: 7.71, p = 2.63 × 10- 7) gene regions. CONCLUSIONS: This exploratory GWAS yielded suggestive candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.

Qualitative study of comprehension of heritability in genomics studies among the Yoruba in Nigeria.

BACKGROUND: With growth of genomics research in Africa, concern has arisen about comprehension and adequacy of informed consent given the highly technical terms used in this field. We therefore decided to study whether there are linguistic and cultural concepts used to communicate heritability of characters, traits and diseases in an indigenous African population. METHODS: We conducted Focus Group Discussions among 115 participants stratified by sex, age and socio-economic status and Key Informant Interviews among 25 stakeholders and Key Opinion Leaders among Yoruba living in Ibadan, Nigeria. We used Atlas-ti v.8.3.17 software to analyze the data, using thematic approach. RESULTS: The study participants identified several linguistic and cultural concepts including words, proverbs, and aphorisms that are used to describe heritable characters, traits and diseases in their local dialect. These included words that can be appropriated to describe dominant and recessive traits, variations in penetrance and dilution of strength of heritable characteristics by time and inter-marriage. They also suggested that these traits are transmitted by "blood", and specific partner's blood may be stronger than the other regardless of sex. CONCLUSIONS: Indigenous Yoruba populations have words and linguistic concepts that describe the heritability of characters, traits and diseases which can be appropriated to improve comprehension and adequacy of informed consent in genomics research. Our methods are openly available and can be used by genomic researchers in other African communities.

Prevalence and incidence of genital warts and cervical Human Papillomavirus infections in Nigerian women.

BACKGROUND: Genital warts are important causes of morbidity and their prevalence and incidence can be used to evaluate the impact of HPV vaccination in a population. METHODS: We enrolled 1020 women in a prospective cohort study in Nigeria and followed them for a mean (SD) of 9 (4) months. Nurses conducted pelvic examinations and collected ectocervical samples for HPV testing. We used exact logistic regression models to identify risk factors for genital warts. RESULTS: The mean age of study participants was 38 years, 56% (535/962) were HIV-negative and 44% (427/962) were HIV-positive. Prevalence of genital warts at enrolment was 1% (4/535) among HIV-negative women, and 5% (23/427) among HIV-positive women. Of 614 women (307 HIV negative and 307 HIV positive women) for whom we could compute genital wart incidence, it was 515 (95% CI:13-2872) per 100,000 person-years in HIV-negative and 1370 (95% CI:283-4033) per 100,000 person-years in HIV-positive women. HIV was associated with higher risk of prevalent genital warts (OR:7.14, 95% CI:2.41-28.7, p < 0.001) while higher number of sex partners in the past year was associated with increased risk of incident genital warts (OR:2.86, 95% CI:1.04-6.47. p = 0.04). HPV11 was the only HPV associated with prevalent genital warts in this population (OR:8.21, 95% CI:2.47-27.3, p = 0.001). CONCLUSION: Genital warts are common in Nigeria and our results provide important parameters for monitoring the impact of future HPV vaccination programs in the country. HIV infection and number of sexual partners in past year were important risk factors for prevalent and incident genital warts respectively.

Neurodevelopmental Outcomes of Twins Compared With Singleton Children: A Systematic Review.

More than 200 million children aged <5 years fail to reach their full cognitive potential, and children born as twins are particularly at risk. In this article, we review studies that examined differences in the neurodevelopmental outcomes of twins compared to singletons. We searched the Medline database for articles on twins, singletons, neuro, and cognitive development. We also inspected bibliographies of relevant publications to identify related articles from 2011 to 2017. Our search criteria yielded 162 studies, 8 of which met the inclusion criteria. Of the eight studies examined, four were prospective follow-up studies, three were cross-sectional studies, and one was a randomized controlled trial. Five of these studies were carried out in developed countries, and they found no statistically significant difference in neurodevelopmental outcomes among twins and singletons. However, two of the three studies carried out in developing countries found a difference with singletons having significantly higher academic ratings than twins. Studies in which neurodevelopmental outcomes were measured early in life (1-5 years) showed no significant twin-singleton differences, while those in which it was measured later in life showed mixed twin-singleton differences. Overall, these studies may have been underpowered and may not have been optimally designed and implemented. There is need for studies with adequate sample sizes, good design, and optimal measurement of all relevant covariates in order to resolve the conflicting reports in the literature.

A comprehensive examination of breast cancer risk loci in African American women.

Genome-wide association studies have identified 73 breast cancer risk variants mainly in European populations. Given considerable differences in linkage disequilibrium structure between populations of European and African ancestry, the known risk variants may not be informative for risk in African ancestry populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in four regions that better captured risk associations in African American women. In this study of breast cancer in African American women (3016 cases, 2745 controls), we tested an additional 54 novel breast cancer risk variants. Thirty-eight variants (70%) were found to have an association with breast cancer in the same direction as previously reported, with eight (15%) replicating at P < 0.05. Through fine-mapping, in three regions (1q32, 3p24, 10q25), we identified variants that better captured associations with overall breast cancer or estrogen receptor positive disease. We also observed suggestive associations with variants (at P < 5 × 10(-6)) in three separate regions (6q25, 14q13, 22q12) that may represent novel risk variants. Directional consistency of association observed for ∼65-70% of currently known genetic variants for breast cancer in women of African ancestry implies a shared functional common variant at most loci. To validate and enhance the spectrum of alleles that define associations at the known breast cancer risk loci, as well as genome-wide, will require even larger collaborative efforts in women of African ancestry.

Moderate Alcohol Consumption and Chronic Disease: The Case for a Long-Term Trial.

Drinking within recommended limits is highly prevalent in much of the world, and strong epidemiological associations exist between moderate alcohol consumption and risk of several major chronic diseases, including coronary heart disease, diabetes, and breast cancer. In many cases, plausible biological mediators for these associations have been identified in randomized trials, but gold standard evidence that moderate drinking causes or prevents any chronic disease remains elusive and important concerns about available evidence have been raised. Although long-term randomized trials to test the observed associations have been termed impossible, clinical investigators have now successfully completed randomized trials of complex nutritional interventions in a variety of settings, along with trials of alcohol consumption itself of up to 2 years duration. The successful completion of these trials suggests that objections to the execution of a full-scale, long-term clinical trial of moderate drinking on chronic disease are increasingly untenable. We present potential lessons learned for such a trial and discuss key features to maximize its feasibility and value.

Prevalence and correlates of leisure-time physical activity among Nigerians.

BACKGROUND: Physical inactivity levels are rising in many countries with major implications for the prevalence of non-communicable diseases and the general health of the population worldwide. We conducted this study to examine leisure-time physical activity levels among African adults in an urban setting. METHODS: We conducted a cross-sectional study among a random sample of 1,058 adults at a government worksite, in Abuja, an urban Nigerian city. We used log-binomial regression models to estimate the multivariable-adjusted associations of correlates of physical activity. RESULTS: The mean age of the study population was 42 ± 9.3 years, 60% were men and 40% were women. The mean metabolic equivalent hours per week for all the participants was 6.8 ± 7.2. In univariate analysis comparing the lowest to highest tertiles of physical activity, the prevalence ratio (PR) and (95% confidence interval, CI) was 0.95 (0.81-1.11) p = 0.49, comparing women to men; compared to those aged <30 years the PR (95% CI) was 0.70 (0.57-0.86), 0.70 (0.58-0.85) and 0.78 (0.63-0.96) for age 30-39, 40-49 and ≥50 years respectively, p for trend = 0.03; compared to those who were normal weight, the PR was 0.93 (0.79-1.10) and 0.90 (0.74-1.09) for overweight and obese persons respectively, p = 0.26. The PR for age was attenuated to non-significant levels in multivariable analyses. Being married was a statistically significant correlate of higher physical activity levels, the PR comparing unmarried to married persons in multivariate analysis was 0.81 (0.67-0.97), p = 0.03. CONCLUSIONS: More than 80% of urban, professional Nigerian adults do not meet the WHO recommendations of physical activity. Urbanized Africans in this study population had low levels of leisure-time physical activity, independent of age, sex and body-mass index. This has major implications for the prevalence of non-communicable diseases in this population.

Obesity epidemic has emerged among Nigerians.

BACKGROUND: Data from the WHO shows that the prevalence of overweight and obesity increased by ~20% between 2002 and 2010 in Nigeria. We conducted this study to examine the correlates of this fast growing epidemic. METHODS: We conducted a cross-sectional study among a random sample of 1058 adults, who were visitors and staff of a government worksite in Abuja, an urban city in Nigeria. The study participants had varying socio-economic status and a wide range of occupations, including skilled labor and professionals. Log-binomial regression models were used to estimate the multivariable-adjusted associations of potential determinants with the prevalence of overweight and obesity. RESULT: The mean age and body-mass index of the study population were 42 years ± (9.3) and 27 kg/m2 ± (4.8). The overall prevalence of overweight or obesity (body-mass index ≥ 25 kg/m2) was 64% (74% of the women and 57% of the men). For women compared to men, the prevalence ratio (PR) and (95% confidence interval, CI) was 1.24 (95% CI 1.08, 1.43, p = 0.004), for overweight, and 2.54 (95% CI 2.08, 3.10, p = <0.0001), for obesity. Individuals aged 40 - 49 years were more likely to be overweight or obese. The PR for overweight and obesity was 1.45 (95% CI 1.07, 1.97), p for age trend = 0.002 and 8.07(95% CI 3.01, 21.66, p for age trend = <0.0001) for those aged 40 - 49 years, compared with those aged <30 years. Compared with the individuals in the lower socio-economic status, the PR for obesity among those in the middle and high socio-economic statuses, were 1.39 (95% CI 1.13, 1.72) and 1.24 (95% CI 0.97, 1.59) respectively, p for trend = 0.003. CONCLUSION: About two-thirds of urban, professional, high socio-economic status Nigerian adults are either overweight or obese. The prevalence of overweight and obesity among this population of adult Nigerians, is as high as it is in the United Kingdom. Female gender and older age were independent predictors of overweight and obesity; while middle or high socio-economic status were independently associated with obesity.

Age-specific prevalence of human papilloma virus infection among Nigerian women.

BACKGROUND: Inconsistent trends in HPV prevalence by age have been described in Africa. We examined the age prevalence pattern and distribution of 37 HPV-DNA types among urban Nigerian women. METHODS: The study population was a sample of 278 women who presented to cervical cancer screening programs in Abuja, Nigeria, between April and August 2012. Using a nurse administered questionnaire, information on demographic characteristics and risk factors of cervical cancer was collected and samples of cervical exfoliated cells were obtained from all participants. Roche Linear Array HPV Genotyping Test® was used to characterize prevalent HPV and log-binomial regression models were used to examine the association between potential correlates and the prevalence of HPV infection. RESULTS: The mean age (SD) of the women enrolled was 38 (8) years. The overall prevalence of HPV was 37%. HPV 35 was the most prevalent HPV type in the study population. Among women age ≤ 30 years, 52% had HPV infection compared to 23% of those women who were older than 45 years (p = 0.006). We observed a significant linear association between age and the prevalence of HPV infections. The prevalence ratio (PR) and 95% confidence interval (CI) was 2.26 (1.17, 4.34) for any HPV infection, 3.83 (1.23, 11.94) for Group 1 HPV (definite carcinogens), and 2.19 (0.99, 4.84) for Group 2a or 2b HPV (probable or possible carcinogens) types, among women aged 18-30 years, compared to women who were older than 45 years. CONCLUSION: The prevalence of HPV infection was highest among younger women and decreased steadily with age among this population of urban Nigerian women.

Voluntary participation and comprehension of informed consent in a genetic epidemiological study of breast cancer in Nigeria.

BACKGROUND: Studies on informed consent to medical research conducted in low or middle-income settings have increased, including empirical investigations of consent to genetic research. We investigated voluntary participation and comprehension of informed consent among women involved in a genetic epidemiological study on breast cancer in an urban setting of Nigeria comparing women in the case and control groups. METHODS: Surveys were administered in face-to-face interviews with 215 participants following their enrollment in the genetic study (106 patients, 109 controls). Audio-taped in-depth interviews were conducted with a sub-sample of 17 (8%) women who completed the survey. RESULTS: The majority of all participants reported being told that participation in the genetic study was voluntary (97%), that they did not feel pressured to participate in the study (99%), and that they could withdraw from the study (81%). The majority of the breast cancer patients (83%) compared to 58% of women in the control group reported that the study purpose was to learn about the genetic inheritance of breast cancer (OR 3.44; 95% CI =1.66, 7.14, p value = 0.001). Most participants reported being told about study procedures (95%) and study benefits (98%). Sixty-eight percent of the patients, compared to 47% of the control group reported being told about study risks (p-value <0.001). Of the 165 married women, 19% reported asking permission from their husbands to enroll in the breast cancer study; no one sought permission from local elders. In-depth interviews highlight the use of persuasion and negotiation between a wife and her husband regarding study participation. CONCLUSIONS: The global expansion of genetic and genomic research highlights our need to understand informed consent practices for studies in ethnically diverse cultural environments such as Africa. Quantitative and qualitative empirical investigations of the informed consent process for genetic and genomic research will further our knowledge of complex issues associated with communication of information, comprehension, decisional authority and voluntary participation. In the future, the development and testing of innovative strategies to promote voluntary participation and comprehension of the goals of genomic research will contribute to our understanding of strategies that enhance the consent process.

Validity and Reproducibility of a Semiquantitative Food Frequency Questionnaire and Food Picture Book in Nigeria.

Background: Increasing noncommunicable diseases in Nigeria are partly related to dietary factors. However, the lack of validated nutrition assessment tools hinders the conduct of nutritional epidemiology research in this population. Objectives: To develop a Food Frequency Questionnaire (FFQ) and Food Picture Book (FPB) for Nigerian adults, and to assess its reproducibility and validity compared with 24-h dietary recalls (24DRs) during different seasons in the year. Methods: We compiled 202 foods for the FFQ through focus groups and consultations with local dietitians. We created an FPB with standardized food portion images to enhance the accuracy of reports of dietary intakes. We administered the FFQs to 205 purposively selected adults in Ibadan, Nigeria at ∼6 monthly intervals between November 2018 and October 2020. We evaluated the FFQ's reproducibility and validity compared with 24DR across the dry and rainy seasons by examining the consumption of common food and mixed dishes. We computed the Spearman's correlation coefficients (SCC), intraclass correlation coefficients (ICC), and Wilcoxon signed-rank tests, and generated Bland and Altman plots. Results: Overall, we studied 110 women (53.7%) and 95 men (46.3%) with a mean age of 45.0 ± 13.4 y (mean ± SD). The reproducibility tests showed a mean ± SD SCC of 0.39 ± 0.14 and mean ± SD ICC of 0.32 ± 0.12. Higher mean ± SD SCC values were noted for cereal products (0.43 ± 0.09), starchy roots and tubers (0.45 ± 0.17), and soups (0.44 ± 0.20). Conversely, lower mean ± SD SCC values were observed for milk products (0.29 ± 0.02), solid fats (0.29 ± 0.26), and fish (0.22 ± 0.19). Regarding validity tests, the overall mean ± SD SCC was 0.27 ± 0.16 and mean ± SD ICC was 0.26 ± 0.16. We observed seasonal variations in intakes of fruits, cassava flour-based products, and nuts, although most foods did not show significant differences in intakes between seasons. Conclusions: Our FFQ and FPB demonstrated moderate correlations and seasonal variations in intakes of certain foods, emphasizing the need to account for seasonality in dietary intakes in nutritional studies in Nigeria and similar countries.

Association Between Cervical Inflammatory Mediators and Prevalent Cervical Human Papillomavirus Infection.

PURPOSE: Inflammatory mediators are important regulators of immune response and can modulate the inflammation caused by viral infections, including human papillomavirus (HPV). In this study, we evaluated the association between cervical immune mediators, including chemokines, cytokines, and growth factors with HPV infections. MATERIALS AND METHODS: We used a nonmagnetic bead-based multiplex assay to determine 27 immune mediators in cervical secretions collected from 275 women in a prospective longitudinal cohort design. All the study participants were age 18 years or older, had a history of vaginal sexual intercourse, were not currently pregnant, and had no history of cervical disease or hysterectomy. RESULTS: The mean (±standard deviation) age of the participants was 41 (±8) years, and about half (51% [141/275]) were HPV-positive, of whom 7% (10/141) had low-risk HPV (lrHPV), 61% (86/141) had high-risk HPV (hrHPV), and 32% (45/141) had both lrHPV and hrHPV infections. Higher concentrations of some immune mediators were associated with HPV infections, including eotaxin, interferon-gamma, interleukin (IL)-1ß, IL-2, IL-4, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, macrophage inflammatory protein (MIP)-1α, MIP-1ß, regulated upon activation normal T-cell expressed and secreted (RANTES), and tumor necrosis factor (TNF)-α and any HPV; IL-2, IL-4, IL-5, IL-7, IL-10, IL-12p70, and IL-13 and lrHPV; and eotaxin, interferon, IL-1B, IL-4, IL-7, IL-8, IL-9, IL-10, IL-13, IL-15, MIP-1α, MIP-1ß, RANTES, TNF-α concentrations, and hrHPV infections. Higher concentrations of granulocyte macrophage colony-stimulating factor, IL-1 receptor antagonist (IL-1Ra), and monocyte chemotactic protein-1 (MCP-1) were associated with reduced odds of any HPV, while IL-1Ra and MCP-1 were associated with reduced odds of hrHPV infections. CONCLUSION: Several chemokines, cytokines, and growth factors are associated with group-specific HPV infections in this population of women. These important findings contribute to the understanding of the immune response to HPV, cytokine profiles and their potential implications for cervical pathogenesis, and can guide future research in this field.

Correction: A Randomized Controlled Trial to Examine the Relationship Between Peer Mentoring for Physical Activity and Cardiometabolic Health.

[This corrects the article DOI: 10.5334/joc.1268.].

Genome, HLA and polygenic risk score analyses for prevalent and persistent cervical human papillomavirus (HPV) infections.

Genetic variants that underlie susceptibility to cervical high-risk human papillomavirus (hrHPV) infections are largely unknown. We conducted discovery genome-wide association studies (GWAS), replication, meta-analysis and colocalization, generated polygenic risk scores (PRS) and examined the association of classical HLA alleles and cervical hrHPV infections in a cohort of over 10,000 women. We identified genome-wide significant variants for prevalent hrHPV around LDB2 and for persistent hrHPV near TPTE2, SMAD2, and CDH12, which code for proteins that are significantly expressed in the human endocervix. Genetic variants associated with persistent hrHPV are in genes enriched for the antigen processing and presentation gene set. HLA-DRB1*13:02, HLA-DQB1*05:02 and HLA-DRB1*03:01 were associated with increased risk, and HLA-DRB1*15:03 was associated with decreased risk of persistent hrHPV. The analyses of peptide binding predictions showed that HLA-DRB1 alleles that were positively associated with persistent hrHPV showed weaker binding with peptides derived from hrHPV proteins and vice versa. The PRS for persistent hrHPV with the best model fit, had a P-value threshold (PT) of 0.001 and a p-value of 0.06 (-log10(0.06) = 1.22). The findings of this study expand our understanding of genetic risk factors for hrHPV infection and persistence and highlight the roles of MHC class II molecules in hrHPV infection.

Untargeted metabolomic profiling reveals molecular signatures associated with type 2 diabetes in Nigerians.

BACKGROUND: Type 2 diabetes (T2D) has reached epidemic proportions globally, including in Africa. However, molecular studies to understand the pathophysiology of T2D remain scarce outside Europe and North America. The aims of this study are to use an untargeted metabolomics approach to identify: (a) metabolites that are differentially expressed between individuals with and without T2D and (b) a metabolic signature associated with T2D in a population of Sub-Saharan Africa (SSA). METHODS: A total of 580 adult Nigerians from the Africa America Diabetes Mellitus (AADM) study were studied. The discovery study included 310 individuals (210 without T2D, 100 with T2D). Metabolites in plasma were assessed by reverse phase, ultra-performance liquid chromatography and mass spectrometry (RP)/UPLC-MS/MS methods on the Metabolon Platform. Welch's two-sample t-test was used to identify differentially expressed metabolites (DEMs), followed by the construction of a biomarker panel using a random forest (RF) algorithm. The biomarker panel was evaluated in a replication sample of 270 individuals (110 without T2D and 160 with T2D) from the same study. RESULTS: Untargeted metabolomic analyses revealed 280 DEMs between individuals with and without T2D. The DEMs predominantly belonged to the lipid (51%, 142/280), amino acid (21%, 59/280), xenobiotics (13%, 35/280), carbohydrate (4%, 10/280) and nucleotide (4%, 10/280) super pathways. At the sub-pathway level, glycolysis, free fatty acid, bile metabolism, and branched chain amino acid catabolism were altered in T2D individuals. A 10-metabolite biomarker panel including glucose, gluconate, mannose, mannonate, 1,5-anhydroglucitol, fructose, fructosyl-lysine, 1-carboxylethylleucine, metformin, and methyl-glucopyranoside predicted T2D with an area under the curve (AUC) of 0.924 (95% CI: 0.845-0.966) and a predicted accuracy of 89.3%. The panel was validated with a similar AUC (0.935, 95% CI 0.906-0.958) in the replication cohort. The 10 metabolites in the biomarker panel correlated significantly with several T2D-related glycemic indices, including Hba1C, insulin resistance (HOMA-IR), and diabetes duration. CONCLUSIONS: We demonstrate that metabolomic dysregulation associated with T2D in Nigerians affects multiple processes, including glycolysis, free fatty acid and bile metabolism, and branched chain amino acid catabolism. Our study replicated previous findings in other populations and identified a metabolic signature that could be used as a biomarker panel of T2D risk and glycemic control thus enhancing our knowledge of molecular pathophysiologic changes in T2D. The metabolomics dataset generated in this study represents an invaluable addition to publicly available multi-omics data on understudied African ancestry populations.

HIV associated high-risk HPV infection among Nigerian women.

BACKGROUND: In developed countries, the incidence of cervical cancer has remained stable in HIV+ women but the prevalence and multiplicity of high-risk HPV (hrHPV) infection, a necessary cause of cervical cancer, appears different comparing HIV+ to HIV- women. Little is known about HIV and HPV co-infection in Africa. METHODS: We enrolled women presenting at our cervical cancer screening program in Abuja, Nigeria between April and August 2012, and collected information on demographic characteristics, risk factors of HPV infection and samples of exfoliated cervical cells. We used Roche Linear Array HPV Genotyping Test® to characterize prevalent HPV and logistic regression models to estimate the association between HIV and the risk of hrHPV infection. RESULTS: There were 278 participants, 54% (151) were HIV+, 40% (111) were HIV-, and 6% (16) had unknown HIV status. Of these, data from 149 HIV+ and 108 HIV- women were available for analysis. The mean ages (± SD) were 37.6 (± 7.7) years for HIV+ and 36.6 (± 7.9) years for HIV- women (p-value = 0.34). Among the HIV+ women, HPV35 (8.7%) and HPV56 (7.4%) were the most prevalent hrHPV, while HPV52 and HPV68 (2.8%, each) were the most prevalent hrHPV types among HIV- women. The multivariate prevalence ratio for any hrHPV and multiple hrHPV infections were 4.18 (95% CI 2.05 - 8.49, p-value <0.0001) and 6.6 (95% CI 1.49 - 29.64, p-value 0.01) respectively, comparing HIV + to HIV- women, adjusted for age, and educational level. CONCLUSIONS: HIV infection was associated with increased risk of any HPV, hrHPV and multiple HPV infections. Oncogenic HPV types 35, 52, 56 and 68 may be more important risk factors for cervical pre-cancer and cancer among women in Africa. Polyvalent hrHPV vaccines meant for African populations should protect against other hrHPV types, in addition to 16 and 18.

Mastectomy for management of breast cancer in Ibadan, Nigeria.

BACKGROUND: Modified radical mastectomy remains the standard therapeutic surgical operation for breast cancer in most parts of the world. This retrospective study reviews mastectomy for management of breast cancer in a surgical oncology division over a ten year period. METHODS: We reviewed the case records of consecutive breast cancer patients who underwent mastectomy at the Surgical Oncology Division, University College Hospital (UCH) Ibadan between November 1999 and October 2009. RESULTS: Of the 1226 newly diagnosed breast cancer patients over the study period, 431 (35.2%) patients underwent mastectomy making an average of 43 mastectomies per year. Most patients were young women, premenopausal, had invasive ductal carcinoma and underwent modified radical mastectomy as the definitive surgical treatment. Prior to mastectomy, locally advanced tumors were down staged in about half of the patients that received neo-adjuvant combination chemotherapy. Surgical complication rate was low. The most frequent operative complication was seroma collection in six percent of patients. The average hospital stay was ten days and most patients were followed up at the surgical outpatients department for about two years post-surgery. CONCLUSIONS: There was low rate of mastectomy in this cohort which could partly be attributable to late presentation of many patients with inoperable local or metastatic tumors necessitating only palliative or terminal care. Tumor down-staging with neo-adjuvant chemotherapy enhanced surgical loco-regional tumor control in some patients. The overall morbidity and the rates of postoperative events were minimal. Long-term post-operative out-patients follow-up was not achieved as many patients were lost to follow up after two years of mastectomy.

Pattern of dietary carbohydrate intake among urbanized adult Nigerians.

As the nutrition transition continues in Africa, it is crucial to identify population-specific dietary patterns. Healthy diets may then be promoted for prevention and alleviation of the chronic disease burden associated with nutrition. Using a semi-quantitate food frequency questionnaire, we conducted a cross-sectional study and computed the proportions of foods commonly consumed, and collected data on anthropometric characteristics. The median total energy intake per day from these carbohydrate sources was 1034 kcal (interquartile range (IOR) 621.5-1738.6 kcal). The main carbohydrate food eaten was rice (48.6%) followed by fufu (30.5%) and bread (13.1%). The prevalence of overweight and obesity was 63%, and 73% of the women in the study were either overweight or obese compared to 56% of men. Our study showed that parboiled long grain white rice is now the most commonly consumed carbohydrate by urbanized Nigerians. Other traditional carbohydrate foods are still consumed frequently and remain quite popular.