The Impact of Conventional Stroke Risk Factors on Early and Late Onset Ischemic Stroke: a Mendelian Randomization Study.

Objective: Although stroke incidence is decreasing in older ages, it is increasing in young adults. While these divergent trends in stroke incidence are at least partially attributable to diverging prevalence trends in stoke risk factors, age-dependent differences in the impact of stroke risk factors on stroke may also contribute. To address this issue, we utilized Mendelian Randomization (MR) to assess differences in the association of stroke risk factors between early onset ischemic stroke (EOS) and late onset ischemic stroke (LOS). Methods: We employed a two-sample MR design with inverse variance weighting as the primary method of analysis. Using large publicly available genome-wide association summary results, we calculated MR estimates for conventional stroke risk factors (body mass index, total, HDL-and LDL-cholesterol, triglycerides, type 2 diabetes, systolic and diastolic blood pressure, and smoking) in EOS cases (onset 18-59 years, n = 6,728) and controls from the Early Onset Stroke Consortium and in LOS cases (onset ≥ 60 years, n = 9,272) and controls from the Stroke Genetics Network. We then compared odds ratios between EOS and LOS, stratified by TOAST subtypes, to determine if any differences observed between effect sizes could be attributed to differences in the distribution of stroke subtypes. Results: EOS was significantly associated with all risk factors except for total cholesterol levels, and LOS was associated with all risk factors except for triglyceride and total cholesterol levels. The associations of BMI, DBP, SBP, and HDL-cholesterol were significantly stronger in EOS than LOS (all p < 0.004). The differential distribution of stroke subtypes could not explain the difference in effect size observed between EOS and LOS. Conclusion: These results suggest that interventions targeted at lowering body mass index and blood pressure may be particularly important for reducing stroke risk in young adults.

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.

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.

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.

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.

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.

Leisure-time physical activity is associated with reduced risks of breast cancer and triple negative breast cancer in Nigerian women.

BACKGROUND: Leisure-time physical activity(LTPA) is associated with a reduced risk of breast cancer, but this has less been investigated by cancer subtypes in Africans living in Sub-Saharan Africa(SSA). We examined the associations between LTPA and breast cancer including its subtypes in Nigerian women and explored the effect modification of body size on such associations. METHODS: The sample included 508 newly diagnosed primary invasive breast cancer cases and 892 controls from the Nigerian Integrative Epidemiology of Breast Cancer(NIBBLE) Study. Immunohistochemical(IHC) analysis was available for 294 cases. Total metabolic equivalents(METs) per hour/week of LTPA were calculated and divided by quartiles(Q1 <3.75, Q2:3.75-6.69, Q3:6.70-14.74, Q4:14.75 ≤). We applied logistic regressions to estimate the adjusted Odds Ratios(ORs) between LTPA and breast cancer and by its molecular subtypes and whether age-adjusted associations are modified by BMI. RESULTS: The mean age(Mean±SD) of cases vs. controls(45.5 ± 11.1vs.40.1 ± 9.0) was higher, and the mean total METs hour/week was higher in controls vs. cases(11.9 ± 14.9vs.8.3 ± 11.1,p-value<0.001). Overall, 43.2%(N = 127/294) were classified as HRP, and 41.8%(N = 123/294) as TNBC. Women in the higher LTPA quartiles(Q3-Q4) vs. Q1 had lower odds of having breast cancer(ORQ4vs.Q1=0.51,95%CI:0.35-0.74) and TNBC(ORQ4vs.Q1=0.51, 95%CI:0.27-0.96), but not HRP(ORQ4vs.Q1=0.61,95%CI:0.34-1.09) after adjusting for age, age at first menarche, body size, breastfeeding, menopausal, parity, contraceptives, demographics, alcohol, smoking, and physical activity at home and work. Lastly, LTPA and its age-adjusted association with breast cancer was more pronounced in women with BMI< 30 vs. BMI 30 + . CONCLUSIONS: LTPA may reduce the risk of breast cancer, especially TNBC, which is the more aggressive and prevalent molecular subtype of breast cancer in SSA.

Different human papillomavirus types share early natural history transitions in immunocompetent women.

Necessary stages of cervical carcinogenesis include acquisition of a carcinogenic human papillomavirus (HPV) type, persistence associated with the development of precancerous lesions, and invasion. Using prospective data from immunocompetent women in the Guanacaste HPV Natural History Study (NHS), the ASCUS-LSIL Triage Study (ALTS) and the Costa Rica HPV Vaccine Trial (CVT), we compared the early natural history of HPV types to inform transition probabilities for health decision models. We excluded women with evidence of high-grade cervical abnormalities at any point during follow-up and restricted the analysis to incident infections in all women and prevalent infections in young women (aged <30 years). We used survival approaches accounting for interval-censoring to estimate the time to clearance distribution for 20 529 HPV infections (64% were incident and 51% were carcinogenic). Time to clearance was similar across HPV types and risk classes (HPV16, HPV18/45, HPV31/33/35/52/58, HPV 39/51/56/59 and noncarcinogenic HPV types); and by age group (18-29, 30-44 and 45-54 years), among carcinogenic and noncarcinogenic infections. Similar time to clearance across HPV types suggests that relative prevalence can predict relative incidence. We confirmed that there was a uniform linear association between incident and prevalent infections for all HPV types within each study cohort. In the absence of progression to precancer, we observed similar time to clearance for incident infections across HPV types and risk classes. A singular clearance function for incident HPV infections has important implications for the refinement of microsimulation models used to evaluate the cost-effectiveness of novel prevention technologies.

A matched case-control study of bean intake and breast cancer risk in urbanized Nigerian women.

PURPOSE: Bean intake has been associated with reduced risk of breast cancer, however; only a few studies considered molecular subtypes status and none in African women living in Sub-Saharan Africa (SSA). Therefore, the purpose of this study was to examine the associations between dietary intake of beans and breast cancer including its subtypes in Nigerian women. METHODS: Overall, 472 newly diagnosed patients with primary invasive breast cancer were age-matched (± 5 years) with 472 controls from the Nigerian Integrative Epidemiology of Breast Cancer (NIBBLE) Study from 01/2014 to 07/2016. We collected the dietary intake of beans using a food frequency questionnaire (FFQ). Beans_alone intake was categorized into three levels never (never in the past year), low (≤ 1 portion/week), and high intake (> 1 portion/week). We used conditional and unconditional logistic regression models to estimate the Odds Ratio (OR) and 95% Confidence Intervals (CI) of beans_alone intake and the risk of breast cancer and by its molecular subtypes, respectively. RESULTS: The mean (SD) age of cases was 44.4(10.0) and of controls was 43.5(9.5) years. In the case group, more than half (51.1%) have never consumed beans_alone in the past year compared to 39.0% in the control group. The multivariable models showed inverse associations between beans_alone (high vs. none) and breast cancer (OR = 0.55; 95%CI: 0.36-0.86, p-trend = 0.03), triple-negative (OR = 0.51 95%CI: 0.28-0.95, p-trend = 0.02) and marginally associated with hormone receptor-positive (OR = 0.53, 95%CI: 0.29-0.96, p-trend = 0.06). CONCLUSION: Dietary intake of beans_alone may play a significant role in reducing the incidence of breast cancer, particularly of the more aggressive molecular subtype, triple-negative, in African women living in SSA.

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.

Dietary Intake and Cancer in Sub-Saharan Africa: A Critical Review of Epidemiological Studies.

Cancer incidence is rising rapidly in Sub-Saharan Africa (SSA). Dietary intake is an established risk factor for certain cancers but only a few epidemiological studies have been conducted in SSA. This study systematically reviewed and summarized the published literature on this issue and identified gaps that can be addressed in future research. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and literature searched was conducted until 11/2/2021. Out of the 5,457 potential references, we reviewed 19 eligible studies: 17 case-controls, two cross-sectionals and no cohort study. South Africa and Kenya conducted the majorities of the studies. The commonest studied cancers were esophageal (9/19), colorectal (4/19) and breast (4/19). Only four studies utilized a validated Food Frequency Questionnaire (FFQ). Although most studies (16/19) reported associations between dietary intake and cancer risks, they were lacking important confounders including total energy intake, multivitamin intake, body fat measures, physical-activity, smoking, and alcohol. Despite rapidly expanding cases of cancer associated with diet, the existent evidence on diet-cancer relationship is too scarce to deduce solid conclusions. There is a need for large cohorts with comprehensive datasets, validated dietary instruments while using advanced statistical analyses that can provide further insights into the imperative links between African diet and cancer risk.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2022.2032217 .

A proposed new generation of evidence-based microsimulation models to inform global control of cervical cancer.

Health decision models are the only available tools designed to consider the lifetime natural history of human papillomavirus (HPV) infection and pathogenesis of cervical cancer, and the estimated long-term impact of preventive interventions. Yet health decision modeling results are often considered a lesser form of scientific evidence due to the inherent needs to rely on imperfect data and make numerous assumptions and extrapolations regarding complex processes. We propose a new health decision modeling framework that de-emphasizes cytologic-colposcopic-histologic diagnoses due to their subjectivity and lack of reproducibility, relying instead on HPV type and duration of infection as the major determinants of subsequent transition probabilities. We posit that the new model health states (normal, carcinogenic HPV infection, precancer, cancer) and corollary transitions are universal, but that the probabilities of transitioning between states may vary by population. Evidence for this variability in host response to HPV infections can be inferred from HPV prevalence patterns in different regions across the lifespan, and might be linked to different average population levels of immunologic control of HPV infections. By prioritizing direct estimation of model transition probabilities from longitudinal data (and limiting reliance on model-fitting techniques that may propagate error when applied to multiple transitions), we aim to reduce the number of assumptions for greater transparency and reliability. We propose this new microsimulation model for critique and discussion, hoping to contribute to models that maximally inform efficient strategies towards global cervical cancer elimination.

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.

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.

The Moderate Alcohol and Cardiovascular Health Trial (MACH15): Design and methods for a randomized trial of moderate alcohol consumption and cardiometabolic risk.

BACKGROUND: Observational studies have documented lower risks of coronary heart disease and diabetes among moderate alcohol consumers relative to abstainers, but only a randomized clinical trial can provide conclusive evidence for or against these associations. AIM: The purpose of this study was to describe the rationale and design of the Moderate Alcohol and Cardiovascular Health Trial, aimed to assess the cardiometabolic effects of one alcoholic drink daily over an average of six years among adults 50 years or older. METHODS: This multicenter, parallel-arm randomized trial was designed to compare the effects of one standard serving (∼11-15 g) daily of a preferred alcoholic beverage to abstention. The trial aimed to enroll 7800 people at high risk of cardiovascular disease. The primary composite endpoint comprised time to the first occurrence of non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalized angina, coronary/carotid revascularization, or total mortality. The trial was designed to provide >80% power to detect a 15% reduction in the risk of the primary outcome. Secondary outcomes included diabetes. Adverse effects of special interest included injuries, congestive heart failure, alcohol use disorders, and cancer. RESULTS: We describe the design, governance, masking issues, and data handling. In three months of field center activity until termination by the funder, the trial randomized 32 participants, successfully screened another 70, and identified ∼400 additional interested individuals. CONCLUSIONS: We describe a feasible design for a long-term randomized trial of moderate alcohol consumption. Such a study will provide the highest level of evidence for the effects of moderate alcohol consumption on cardiovascular disease and diabetes, and will directly inform clinical and public health guidelines.

Cancers Attributable to Overweight and Obesity From 2012 to 2014 in Nigeria: A Population-Based Cancer Registry Study.

Background: Overweight and obesity are known risk factors for chronic diseases including cancers. In this study, we evaluated the age standardized incidence rates (ASR) and proportion of cancers attributable to overweight and obesity in Nigeria. Methods: We obtained incidence data from the databases of two population-based cancer registries (PBCRs) in Nigeria (Abuja and Enugu cancer registries), on cancer site for which there is established evidence of an association with overweight or obesity based on the International Agency for Research on Cancer (IARC) and the World Cancer Research Fund (WCRF) classification. We analyzed the data using population attributable fraction (PAF) for overweight or obesity associated cancers calculated using prevalence data and relative risk estimates in previous studies. Results: The two PBCRs reported 4,336 new cancer cases (ASR 113.9 per 100,000) from 2012 to 2014. Some 21% of these cancers were associated with overweight and obesity. The ASR for overweight and obesity associated cancers was 24.5 per 100,000; 40.7 per 100,000 in women and 8.2 per 100,000 in men. Overall, only 1.4% of incident cancers were attributable to overweight and obesity. The ASR of cancers attributable to overweight and obesity was 2.0 per 100,000. Postmenopausal breast cancer was the most common cancer attributable to overweight and obesity (n = 25; ASR 1.2 per 100,000). Conclusion: Our results suggest that a small proportion of incident cancer cases in Nigeria are potentially preventable by maintaining normal body weight. The burden of cancer attributed to overweight and obesity in Nigeria is relatively small, but it may increase in future.