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.

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.].

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.

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.

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.

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.

Population-based study of the reproductive risk factors for transvaginal ultrasound diagnosed uterine fibroids in Nigerian women.

There has been no previous systematic, epidemiological study of the reproductive risk factors for uterine fibroids (UF) in African populations despite African women having the highest burden of UF in the world. Improved knowledge of the associations between UF and reproductive factors would contribute to better understanding of the etiology of UF and may suggest novel opportunities for prevention and therapeutic interventions. We used nurse administered questionnaires to survey the demographic and reproductive risk factors of UF among 484 women who are members of the African Collaborative Center for Microbiome and Genomics Research (ACCME) Study Cohort in central Nigeria, and who had transvaginal ultrasound diagnosis (TVUS). We used logistic regression models to the evaluate associations between reproductive risk factors and UF, adjusted for significant covariates. In our multivariable logistic regression models, we found inverse associations with number of children (OR = 0.83, 95%CI = 0.74-0.93, p-value = 0.002), parity (OR = 0.41, 95%CI = 0.24-0.73, p-value = 0.002), history of any type of abortion (OR = 0.53, 95%CI = 0.35-0.82, p-value = 0.004), duration of use of Depot Medroxyprogesterone Acetate (DMPA) (p-value for trend = 0.02), menopausal status (OR = 0.48, 95%CI = 0.27-0.84, p-value = 0.01), and a non-linear positive association with age (OR = 1.04, 95%CI = 1.01-1.07, p-value = 0.003). Other reproductive risk factors that have been reported in other populations (age at menarche and menopause, and oral contraceptives) were not associated with UF in this study. Our study confirms some of the reproductive risk factors for UF that have been found in other populations and shows that some of them are stronger in the Nigerian population. The associations we found with DMPA suggest opportunities for further research to understand the mechanisms of action of progesterone and its analogues in the etiology of UF, their potential use for prevention and treatment of UF.

Dataset for vaginal human papillomavirus infection among adolescent and early adult girls in Jos, Nigeria.

OBJECTIVES: To assess risk factors for HPV infection, determine knowledge about HPV vaccines, assess willingness to receive the HPV vaccine among adolescent and early adult girls in Nigeria, we administered a structured questionnaire. We also collected samples to determine the prevalence and patterns of HPV infections. DATA DESCRIPTION: The dataset contains the responses of 205 participants from 10 randomly selected public and private secondary schools in Jos, Nigeria. The data includes information on risk factors for HPV infections such as sexual behaviours, knowledge about HPV vaccine and willingness to receive the vaccine. This is valuable information that can be compared to data from studies in other environments or to determine changes in the pattern of risk factors and HPV prevalence in this population over time.

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

Background: Studies examining the effect of peer mentoring on physical activity levels have been conducted in mostly elderly and young populations, and the results have been inconsistent. This study examined the impact of one-on-one peer mentoring on physical activity and cardiometabolic parameters in urban adults. Methods: The study participants were 353 overweight or obese adults residing in Abuja, Nigeria. They were randomized into two groups, peer-mentored (n = 128) and a control (n = 225) group. All the participants received nutritional counseling and were invited to attend instructor-led physical activity sessions each week for six months. Differences in the frequency, duration, and intensity of physical activity and cardiometabolic parameters, including body fat, muscle mass and lipids, were evaluated within and between the groups with t and rank sum tests. Results: At the end of the study period, the average time spent on physical activity increased significantly by 14% (p = 0.006), and the average time spent on vigorous physical activity increased by 99% (p = 0.003) compared to baseline for participants in the peer-mentored group. For those in the control group, the average time spent on physical activity decreased significantly by 7% (p = 0.03), while the average time spent on vigorous physical activity increased by 30%, but this was not statistically significant (p = 0.34). In both groups, there were significant improvements in the total cholesterol, low- and high-density lipoproteins and triglycerides levels, at the end of the study period, compared to baseline. Conclusions: In these overweight or obese adults, we observed that peer mentoring was positively associated with increased physical activity. Peer mentoring also holds great promise for improving cardiometabolic health and promoting a healthy lifestyle in adults.

The promise of data science for health research in Africa.

Data science health research promises tremendous benefits for African populations, but its implementation is fraught with substantial ethical governance risks that could thwart the delivery of these anticipated benefits. We discuss emerging efforts to build ethical governance frameworks for data science health research in Africa and the opportunities to advance these through investments by African governments and institutions, international funding organizations and collaborations for research and capacity development.

Population-based study of the reproductive risk factors for Transvaginal Ultrasound diagnosed Uterine Fibroids in Nigerian women.

Objective: There has been no previous systematic, epidemiological study of the reproductive risk factors for uterine fibroids (UF) in African populations despite African women having the highest burden of UF in the world. Improved knowledge of the associations between UF and reproductive factors would contribute to better understanding of the etiology of UF and may suggest novel opportunities for prevention and therapeutic interventions. Design: We used nurse administered questionnaires to survey the demographic and reproductive risk factors of UF among 484 women who are members of the African Collaborative Center for Microbiome and Genomics Research (ACCME) Study Cohort in central Nigeria, and who had transvaginal ultrasound diagnosis (TVUS). We used logistic regression models to the evaluate associations between reproductive risk factors and UF, adjusted for significant covariates. Results: In our multivariable logistic regression models, we found inverse associations with number of children (OR = 0.83, 95%CI = 0.74-0.93, p-value = 0.002), parity (OR = 0.41, 95%CI = 0.24-0.73, p-value = 0.02), history of any type of abortion (OR = 0.53, 95%CI = 0.35-0.82, p-value = 0.004), duration of use of Depot Medroxyprogesterone Acetate (DMPA) (p-value for trend = 0.02), menopausal status (OR = 0.48, 95%CI = 0.27-0.84, p-value = 0.01), and a non-linear positive association with age (OR = 1.04, 95%CI = 1.01-1.07, p-value = 0.003). Other reproductive risk factors that have been reported in other populations (age at menarche and menopause, and oral contraceptives) were not associated with UF in this study. Conclusion: Our study confirms the reproductive risk factors for UF that have been found in other populations and shows that some of them are stronger in the Nigerian population. The associations we found with DMPA suggest opportunities for further research to understand the mechanisms of action of progesterone and its analogues in the etiology of UF, their potential use for prevention and treatment of UF.

Validation of self-report of uterine fibroid diagnosis using a transvaginal ultrasound scan.

Self-report of uterine fibroids (UF) has been used for epidemiologic research in different environments. Given the dearth of studies on the epidemiology of UF in Sub-Saharan Africa (SSA), it is valuable to evaluate its performance as a potential tool for much needed research on this common neoplasm in SSA women. We conducted a cross-sectional study of self-report of UF compared with transvaginal ultrasound diagnosis (TVUS) among 486 women who are members of the African Collaborative Center for Microbiome and Genomics Research (ACCME) Study Cohort in central Nigeria. We used log-binomial regression models to compute the classification, sensitivity, specificity, and predictive values of self-report compared to TVUS, adjusted for significant covariates. The prevalence of UF on TVUS was 45.1% (219/486) compared to 5.4% (26/486) based on self-report of abdominal ultrasound scan and 7.2% (35/486) based on report of healthcare practitioner's diagnosis. Self-report correctly classified 39.5% of the women compared to TVUS in multivariable adjusted models. The multivariable adjusted sensitivity of self-report of healthcare worker diagnosis was 38.8%, specificity was 74.5%, positive predictive value (PPV) was 55.6%, and negative predictive value (NPV) was 59.8%. For self-reported abdominal ultrasound diagnosis, the multivariable adjusted sensitivity was 40.6%, specificity was 75.3%, PPV was 57.4%, and NPV was 60.6%. Self-report significantly underestimates the prevalence of UF and is not accurate enough for epidemiological research on UF. Future studies of UF should use population-based designs and more accurate diagnostic tools such as TVUS.

Dataset for Vaginal Human Papillomavirus infection among adolescent and early adult girls in Jos, Nigeria.

Objectives: To assess risk factors for HPV infection, determine knowledge about HPV vaccines, assess willingness to receive the HPV vaccine among adolescent and early adult girls in Nigeria, we administered a structured questionnaire. We also collected samples to determine the prevalence and patterns of HPV infections. Data description: The dataset contains the responses of 205 participants from 10 randomly selected public and private secondary schools in Jos, Nigeria. The data includes information on risk factors for HPV infections such as sexual behaviours, knowledge about HPV vaccine and willingness to receive the vaccine. This is valuable information that can be compared to data from studies in other environments or to determine changes in the pattern of risk factors and HPV prevalence in this population over time.

Epidemiology of uterine fibroid in black African women: a systematic scoping review.

OBJECTIVE: Studies, mainly from high-income countries, suggest that there are ethnic and racial variations in prevalence of uterine fibroids (UF). However, there have been few studies of the epidemiology of UF in sub-Saharan Africa (SSA). We reviewed published articles on the epidemiology of UF in SSA. DESIGN: This was a scoping review of literature. SETTINGS: We searched three databases (PubMed, African Wide Information (EBSCO) and African Journals OnLine (AJOL)). The search for eligible articles was conducted between December 2019 and January 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: To describe the reported prevalence/incidence of, and risk factors for UF in SSA. RESULTS: Of the 1052 articles retrieved, 9 met the inclusion criteria for review. The articles were from Nigeria (4/9), Ghana (2/9), Cameroon (1/9), Kenya (1/9) and South Africa (1/9). Two studies from pathology departments and three studies from radiology departments reported prevalence of UF. We did not find any study on the incidence or genomics of UF in SSA. Of the three studies that reported on the risk factors of UF, only one case-control study that was conducted using retrospective data of attendees at a gynaecological clinic conducted multivariable analysis. CONCLUSION: There is lack of robust epidemiological studies of the prevalence, incidence and risk factors of UF in SSA. There is urgent need to study epidemiological and genomics risk factors of UF in SSA because UF is the most common gynaecological neoplasm in this population where it is associated with significant morbidity and occasional, usually perioperative, mortality.

The African Female Breast Cancer Epidemiology Study Protocol.

Breast cancer is now the commonest cancer in most sub-Saharan African countries. Few studies of the epidemiology and genomics of breast cancer and its molecular subtypes in these countries have been done. The African Female Breast Cancer Epidemiology (AFBRECANE) study, a part of the Human Heredity and Health in Africa (H3Africa) initiative, is designed to study the genomics and epidemiology of breast cancer and its molecular subtypes in Nigerian women. We link recruitment of breast cancer cases at study sites with population-based cancer registries activities to enable ascertainment of the incidence of breast cancer and its molecular subtypes. We use centralized laboratory processing to characterize the histopathological and molecular diagnosis of breast cancer and its subtypes using multiple technologies. By combining genome-wide association study (GWAS) data from this study with that generated from 12,000 women participating in our prospective cohort study of cervical cancer, we conduct GWAS of breast cancer in an entirely indigenous African population. We test associations between dietary intakes and breast cancer and focus on vitamin D which we measure using dietary intakes, serum vitamin D, and Mendelian randomization. This paper describes the AFBRECANE project, its design, objectives and anticipated contributions to knowledge and understanding of breast cancer.

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.

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.

Vaginal microbiota diversity and paucity of Lactobacillus species are associated with persistent hrHPV infection in HIV negative but not in HIV positive women.

The vaginal microbiota is thought to play a role in modulating risk of high-risk human papillomavirus (hrHPV) infection. We examined the relationship between the vaginal microbiota and persistent hrHPV infection in HIV-negative and HIV-positive women. We used 16S-rRNA sequencing to characterize the vaginal microbiota of two serial samples taken six months apart from 211 Nigerian women (67%, 142/211 HIV-positive and 33%, 69/211 HIV-negative) and evaluated the association between the vaginal microbiota and persistent hrHPV infection using generalized estimating equation logistic regression models and linear discriminant analysis effect size (LEfSe) algorithm to identify phylotypic biomarkers of persistent hrHPV infection. The high diversity microbiota, Community State Type IV-B, was the most prevalent in both HIV-negative (38% at baseline, 30% at the follow-up visit) and HIV-positive (27% at baseline, 35% at the follow-up visit) women. The relationship between the vaginal microbiota and persistent hrHPV was modified by HIV status. In HIV-negative women, women with Lactobacillus dominant microbiota had lower odds (OR: 0.35, 95% CI 0.14-0.89, p = 0.03) of persistent hrHPV compared to women with Lactobacillus deficient microbiota. While among HIV-positive women, the odds of being persistently infected with hrHPV was higher in women with Lactobacillus dominant microbiota (OR: 1.25, 95% CI 0.73-2.14 p = 0.41). This difference in effect estimates by HIV was statistically significant (p = 0.02). A high diversity vaginal microbial community with paucity of Lactobacillus species was associated with persistent hrHPV infection in HIV-negative women but not in HIV-positive women.

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.