Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions.

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10-8) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10-5). Fine mapping identified 4,008 CCVs in these regions, of which 1,452 CCVs were located in ovarian cancer-related chromatin marks with significant enrichment in active enhancers, active promoters, and active regions for CCVs from each EOC histotype. Transcriptome-wide association and colocalization analyses across histotypes using tissue-specific and cross-tissue datasets identified 86 candidate susceptibility genes in known EOC risk regions and 32 genes in 23 additional genomic regions that may represent novel EOC risk loci (false discovery rate <0.05). Finally, by integrating genome-wide HiChIP interactome analysis with transcriptome-wide association study (TWAS), variant effect predictor, transcription factor ChIP-seq, and motifbreakR data, we identified candidate gene-CCV interactions at each locus. This included risk loci where TWAS identified one or more candidate susceptibility genes (e.g., HOXD-AS2, HOXD8, and HOXD3 at 2q31) and other loci where no candidate gene was identified (e.g., MYC and PVT1 at 8q24) by TWAS. In summary, this study describes a functional framework and provides a greater understanding of the biological significance of risk alleles and candidate gene targets at EOC susceptibility loci identified by a genome-wide association study.

chromMAGMA: regulatory element-centric interrogation of risk variants.

Candidate causal risk variants from genome-wide association studies reside almost exclusively in noncoding regions of the genome and innovative approaches are necessary to understand their biological function. Multi-marker analysis of genomic annotation (MAGMA) is a widely used program that nominates candidate risk genes by mapping single-nucleotide polymorphism summary statistics from genome-wide association studies to gene bodies. We augmented MAGMA to create chromatin-MAGMA (chromMAGMA), a method to nominate candidate risk genes based on the presence of risk variants within noncoding regulatory elements (REs). We applied chromMAGMA to a genetic susceptibility dataset for epithelial ovarian cancer (EOC), a rare gynecologic malignancy characterized by high mortality. This identified 155 unique candidate EOC risk genes across five EOC histotypes; 83% (105/127) of high-grade serous ovarian cancer risk genes had not previously been implicated in this EOC histotype. Risk genes nominated by chromMAGMA converged on mRNA splicing and transcriptional dysregulation pathways. chromMAGMA is a pipeline that nominates candidate risk genes through a gene regulation-focused approach and helps interpret the biological mechanism of noncoding risk variants for complex diseases.

Polygenic risk modeling for prediction of epithelial ovarian cancer risk.

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.

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.

High-depth African genomes inform human migration and health.

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals-comprising 50 ethnolinguistic groups, including previously unsampled populations-to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon-but in other genes, variants denoted as 'likely pathogenic' in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health.

Ovarian Cancer Risk Variants Are Enriched in Histotype-Specific Enhancers and Disrupt Transcription Factor Binding Sites.

Quantifying the functional effects of complex disease risk variants can provide insights into mechanisms underlying disease biology. Genome-wide association studies have identified 39 regions associated with risk of epithelial ovarian cancer (EOC). The vast majority of these variants lie in the non-coding genome, where they likely function through interaction with gene regulatory elements. In this study we first estimated the heritability explained by known common low penetrance risk alleles for EOC. The narrow sense heritability (hg2) of EOC overall and high-grade serous ovarian cancer (HGSOCs) were estimated to be 5%-6%. Partitioned SNP heritability across broad functional categories indicated a significant contribution of regulatory elements to EOC heritability. We collated epigenomic profiling data for 77 cell and tissue types from Roadmap Epigenomics and ENCODE, and from H3K27Ac ChIP-seq data generated in 26 ovarian cancer and precursor-related cell and tissue types. We identified significant enrichment of risk single-nucleotide polymorphisms (SNPs) in active regulatory elements marked by H3K27Ac in HGSOCs. To further investigate how risk SNPs in active regulatory elements influence predisposition to ovarian cancer, we used motifbreakR to predict the disruption of transcription factor binding sites. We identified 469 candidate causal risk variants in H3K27Ac peaks that are predicted to significantly break transcription factor (TF) motifs. The most frequently broken motif was REST (p value = 0.0028), which has been reported as both a tumor suppressor and an oncogene. Overall, these systematic functional annotations with epigenomic data improve interpretation of EOC risk variants and shed light on likely cells of origin.

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.

Secular trend in interobserver agreement of VIA diagnosis for cervical cancer screening in Nigeria.

OBJECTIVE: In low resource settings, visual inspection with acetic acid (VIA) by allied health workers, has been suggested as an alternative for cervical cancer screening. However, there are concerns about the objectivity and time to diagnostic concordance with specialists. We evaluated the secular trend in interobserver agreement between nurse providers and a gynecologist/colposcopist over a five-year period. METHODS: Nurses provided VIA screening with digital cervivography to 4,961 participants in five screening clinics from October 2010 to May 2014 in Nigeria in this observational study. Cervigraphs were reviewed at meetings where a gynaecologist/colposcopist made an assessment from the cervigraphs. We used weighted kappa statistics to calculate agreement in diagnosis between nurse providers and the gynecologist/colposcopist; linear regression models to examine overall trend and investigate potential clinic characteristics that may influence agreement; and time series models to characterize month to month variations. RESULTS: Mean age of participants was 37±8 years. Overall agreement was 0.89 at Site D, 0.78 and 0.73 at Sites A and C respectively, 0.50 for Site E and 0.34 for Site C. The number of trainings attended by nurse providers(ß = 0.47,95%CI:0.02-0.93, p = 0.04), high level of engagement by site gynecologists(ß = 0.11,95%CI:0.01-0.21,p = 0.04) were associated with increased agreement; while increasing distance from the coordinating site(ß = -0.47,95%CI:-0.92-0.02,p = 0.04) was associated with decreased agreement. There were no associations between number of years screening clinics were operational(ß = 0.01,95%CI: -0.01-0.03,p = 0.29), cumulative experience of nurse providers(ß = 0.04,95%CI:-0.03-0.12,p = 0.19) and agreement. There were no significant increases in weighted kappa statistics over time for all sites considered. Monthly variations were significant for only one of two sites considered in time series models (AR1 term = -0.40, 95%CI:-0.71-0.09,p = 0.01). CONCLUSION: Our results showed a lack of objectivity, persistent variation and lack of convergence of diagnostic capabilities of nurse led VIA cervical cancer screening with the diagnostic capabilities of a specialist in a cervical cancer screening program in Nigeria.

Clearance of Type-Specific, Low-Risk, and High-Risk Cervical Human Papillomavirus Infections in HIV-Negative and HIV-Positive Women.

Purpose There is a dearth of data on clearance of cervical human papillomavirus (HPV) infection among women in West Africa. We examined the clearance of low-risk (lr) and high-risk (hr) cervical HPV infections, and the factors associated with these measures in HIV-negative and HIV-positive women. Methods We studied 630 Nigerian women involved in a study of HPV infection using short polymerase chain reaction fragment-10 assay and line probe assay-25. Research nurses used a cervical brush to collect samples of exfoliated cervical cells from all the study participants. Cox proportional hazards models were used to estimate associations between HIV and HPV infections. Results The mean age of the study participants was 38 (standard deviation, ± 8) years; 51% were HIV positive. The rate of clearing any HPV infection was 2.0% per month among all women in the study population, 2.5% per month among HIV-negative women, and 1.6% per month, among HIV-positive women. The clearance rate per 1,000 person-months of observation for any lrHPV infection and any hrHPV infection were 9.21 and 8.83, respectively, for HIV-negative women, and 9.38 and 9.37, respectively, for HIV-positive women. In multivariate models, the hazard ratios for HIV-positive compared with HIV-negative women were 0.85 (95% CI, 0.51 to 1.43; P = .55) and 0.95 (95% CI, 0.54 to 1.65; P = .85) for cleared infections with any lrHPV and any hrHPV, respectively. The hazard ratio for HIV-positive compared with HIV-negative women was 0.39 (95% CI, 0.17 to 0.88; P = .02) for cleared infections with any multiple HPV and 0.13 (95% CI, 0.03 to 0.58; P = .007) for cleared infections with multiple hrHPV. Conclusion In this study population, we observed that HIV-positive women were less likely to clear infections with multiple hrHPV types.

Age, HIV status, and research context determined attrition in a longitudinal cohort in Nigeria.

OBJECTIVES: We explored determinants of attrition in a longitudinal cohort study in Nigeria. STUDY DESIGN AND SETTING: We enrolled 1,020 women into a prospective study. Of these, 973 were eligible to return for follow-up. We investigated the determinants of attrition among eligible women using a sequential mixed methods design. We used logistic regression models to compare the baseline characteristics of responders and nonresponders. At the end of the parent study, we conducted four focus group discussions and eight key informant interviews with nonresponders. RESULTS: Of the 973 women included in the quantitative analysis, 26% were nonresponders. From quantitative analysis, older women were less likely to drop out than younger women (reference: women ≤30 years; OR 0.46; 95% confidence interval [CI] 0.30-0.70, P < 0.001 women 31-44 years; and OR 0.31; 95% CI 0.17-0.56, P < 0.001 women ≥45 years). HIV-positive women were also less likely to drop out of the study (OR 0.45; 95% CI 0.33-0.63, P < 0.001). From qualitative analysis, contextual factors that influenced attrition were high cost of participation, therapeutic misconceptions, inaccurate expectations, spousal disapproval, unpleasant side effects, challenges in maintaining contact with participants, and participant difficulties in locating the study clinic. CONCLUSION: Several participant-, research-, and environment-related factors influence attrition. Retention strategies that address these barriers are important to minimize attrition.

Implementation of genomics research in Africa: challenges and recommendations.

BACKGROUND: There is exponential growth in the interest and implementation of genomics research in Africa. This growth has been facilitated by the Human Hereditary and Health in Africa (H3Africa) initiative, which aims to promote a contemporary research approach to the study of genomics and environmental determinants of common diseases in African populations. OBJECTIVE: The purpose of this article is to describe important challenges affecting genomics research implementation in Africa. METHODS: The observations, challenges and recommendations presented in this article were obtained through discussions by African scientists at teleconferences and face-to-face meetings, seminars at consortium conferences and in-depth individual discussions. RESULTS: Challenges affecting genomics research implementation in Africa, which are related to limited resources include ill-equipped facilities, poor accessibility to research centers, lack of expertise and an enabling environment for research activities in local hospitals. Challenges related to the research study include delayed funding, extensive procedures and interventions requiring multiple visits, delays setting up research teams and insufficient staff training, language barriers and an underappreciation of cultural norms. While many African countries are struggling to initiate genomics projects, others have set up genomics research facilities that meet international standards. CONCLUSIONS: The lessons learned in implementing successful genomics projects in Africa are recommended as strategies to overcome these challenges. These recommendations may guide the development and application of new research programs in low-resource settings.

Cancers Attributable to Alcohol Consumption in Nigeria: 2012-2014.

INTRODUCTION: Alcohol consumption has been identified as a risk factor for many cancers but less attention has been paid to the fraction of those cancers that are attributable to alcohol consumption. In this study, we evaluated the incidence and population attributable fraction (PAF) of cancers associated with alcohol consumption in Nigeria. METHODS: We obtained data on incidence of cancers from two population-based cancer registries (PBCRs) in Nigeria and identified cancer sites for which there is strong evidence of an association with alcohol consumption based on the International Agency for Research on Cancer Monograph 100E. We computed the PAF for each cancer site by age and sex, using prevalence and relative risk estimates from previous studies. RESULTS: Between 2012 and 2014 study period, the PBCRs reported 4,336 cancer cases of which 1,627 occurred in males, and 2,709 occurred in females. Of these, a total of 1,808 cancer cases, 339 in males and 1,469 in females, were associated with alcohol intake. The age standardized incidence rate (ASR) of alcohol associated cancers was 77.3 per 100,000. Only 4.3% (186/4,336) of all cancer cases or 10.3% (186/1,808) of alcohol associated cancers were attributable to alcohol consumption. Some 42.5% (79/186) of these cancers occurred in males while 57.5% (107/186) occurred in females. The ASR of cancers attributable to alcohol in this population was 7.2 per 100,000. The commonest cancers attributable to alcohol consumption were cancers of the oral cavity and pharynx in men and cancer of the breast in women. CONCLUSION: Our study shows that 4.3% of incident cancers in Nigeria can be prevented by avoiding alcohol consumption. While the incidence of cancers associated with alcohol intake is high, the proportion attributable to alcohol consumption is much lower suggesting that the number of cancers that may be prevented by eliminating alcohol intake in this population is relatively low.

Attitude to Human Papillomavirus Deoxyribonucleic Acid-Based Cervical Cancer Screening in Antenatal Care in Nigeria: A Qualitative Study.

OBJECTIVES: Human papillomavirus (HPV) deoxyribonucleic acid (DNA)-based testing is increasingly used for cervical cancer screening in developed countries, but the best approach to utilizing it in low- and middle-income countries (LMIC) is unclear. Incorporation of HPV DNA-based testing into routine antenatal care (ANC) is a potential yet poorly explored strategy for cervical cancer screening in LMIC. We explored the attitude of health care workers and pregnant women to the incorporation of HPV DNA-based tests into routine ANC in Nigeria. METHODS: We conducted nine focus group discussions with 82 pregnant women and 13 in-depth interviews with obstetricians and midwives at four health care facilities in Abuja, Nigeria. We used qualitative content analysis to analyze the data and the theory of planned behavior as a theoretical framework to examine the responses. RESULTS: Pregnant women expressed a favorable attitude toward HPV DNA testing for cervical cancer screening as part of routine ANC. Acceptability of this approach was motivated by the expected benefits from early detection and treatment of cervical cancer. The factors most commonly cited as likely to influence acceptability and uptake of HPV DNA-based tests are recommendations by their care providers and mandating testing as part of ANC services. Discussants mentioned lack of awareness and affordability as factors that may inhibit uptake of HPV DNA-based cervical cancer screening. Midwives expressed concerns about the safety of sampling procedure in pregnancy, while obstetricians fully support the integration of HPV DNA-based testing into routine ANC. CONCLUSION: Our results show that incorporating HPV DN-based cervical cancer screening into routine ANC is acceptable to pregnant women and health care providers. Making the test affordable and educating health care workers on its efficacy and safety if performed during ANC will enhance their willingness to recommend it and increase its uptake.

Test-Retest Reliability of Self-Reported Sexual Behavior History in Urbanized Nigerian Women.

BACKGROUND: Studies assessing risk of sexual behavior and disease are often plagued by questions about the reliability of self-reported sexual behavior. In this study, we evaluated the reliability of self-reported sexual history among urbanized women in a prospective study of cervical HPV infections in Nigeria. METHODS: We examined test-retest reliability of sexual practices using questionnaires administered at study entry and at follow-up visits. We used the root mean squared approach to calculate within-person coefficient of variation (CVw) and calculated the intra-class correlation coefficient (ICC) using two way, mixed effects models for continuous variables and [Formula: see text] statistics for discrete variables. To evaluate the potential predictors of reliability, we used linear regression and log binomial regression models for the continuous and categorical variables, respectively. RESULTS: We found that self-reported sexual history was generally reliable, with overall ICC ranging from 0.7 to 0.9; however, the reliability varied by nature of sexual behavior evaluated. Frequency reports of non-vaginal sex (agreement = 63.9%, 95% CI: 47.5-77.6%) were more reliable than those of vaginal sex (agreement = 59.1%, 95% CI: 55.2-62.8%). Reports of time-invariant behaviors were also more reliable than frequency reports. The CVw for age at sexual debut was 10.7 (95% CI: 10.6-10.7) compared with the CVw for lifetime number of vaginal sex partners, which was 35.2 (95% CI: 35.1-35.3). The test-retest interval was an important predictor of reliability of responses, with longer intervals resulting in increased inconsistency (average change in unreliability for each 1 month increase = 0.04, 95% CI = 0.07-0.38, p = 0.005). CONCLUSION: Our findings suggest that overall, the self-reported sexual history among urbanized Nigeran women is reliable.

Persistent Low-Risk and High-Risk Human Papillomavirus Infections of the Uterine Cervix in HIV-Negative and HIV-Positive Women.

BACKGROUND: The prevalence, persistence, and multiplicity of human papillomavirus (HPV) infection appears different comparing HIV-positive to HIV-negative women. In this study, we examined prevalent, persistent, and multiple low- and high-risk cervical HPV infections in HIV-negative and HIV-positive women. METHODS: We studied 1,020 women involved in a study of HPV infection using SPF25/LiPA10. Two study visits were scheduled, at enrollment and 6 months afterward. At each study visit, research nurses used a cervical brush to collect samples of exfoliated cervical cells from the cervical os, from all the study participants. Exact logistic regression models were used to estimate associations between HIV and HPV infections. RESULTS: The mean (SD) age of the study participants was 38 (8) years, 56% were HIV-negative and 44% were HIV-positive. Among HIV-negative women at baseline, single low-risk HPV (lrHPV) infections occurred in 12%; multiple lrHPV in 2%; single high-risk human papillomavirus (hrHPV) infections in 9%, and multiple hrHPV infections in 2%. Single lrHPV infections were persistent in 6%, but there was no persistent multiple lrHPV infections. Single hrHPV infections were persistent in 4% while multiple hrHPV infections were persistent in 0.3%. Among HIV-positive women at baseline, single lrHPV infections occurred in 19%, multiple lrHPV in 6%, single hrHPV infections in 17%, and multiple hrHPV infections occurred in 12%. Single lrHPV infections were persistent in 9%, multiple lrHPV infections in 0.6%, single hrHPV infections in 13%, while multiple hrHPV were persistent in 3%. Prevalent, persistent, and multiple infections were more common in HIV-positive women, compared to HIV-negative women. In multivariate models adjusted for age, marital status, socioeconomic status, age at sexual initiation, and douching, the odds ratios comparing HIV-positive to HIV-negative women, were 2.09 (95% CI 1.47-2.97, p < 0.001) for prevalent lrHPV, 1.26 (95% CI 0.66-2.40, p 0.47) for persistent lrHPV infections, 3.38 (95% CI 2.34-4.87, p < 0.001) for prevalent hrHPV, and 4.49 (95% CI 2.26-8.91, p < 0.001) for persistent hrHPV infections. CONCLUSION: HIV infection was associated with higher prevalence of lrHPV, hrHPV, and persistence hrHPV infections, but not persistent lrHPV infections.

Burden of Cancers Attributable to Infectious Agents in Nigeria: 2012-2014.

INTRODUCTION: Infections by certain viruses, bacteria, and parasites have been identified as risk factors for some cancers. In Nigeria, like many other developing countries, infections remain a leading cause of morbidity and mortality. While there are data on the incidence of different cancers in Nigeria, there has been no study of cancers attributable to infections. This study was carried out to determine the burden of cancers attributable to infections using data from two population-based cancer registries (PBCRs) in Nigeria. METHODS: We obtained data on cancers associated with EBV, human papillomavirus (HPV), hepatitis B and C, HIV, HHV8, Helicobacter pylori, and Schistosoma spp. from the databases of Abuja and Enugu cancer registries in Nigeria. We used population-attributable fraction for infections-associated cancers in developing countries that are based on prevalence data and relative risk estimates from previous studies. RESULTS: The PBCRs reported 4,336 incident cancer cases [age standardized incidence rate (ASR) 113.9 per 100,000] from 2012 to 2014, of which 1,627 (37.5%) were in males and 2,709 (62.5%) were in females. Some 1,030 (23.8%) of these cancers were associated with infections (ASR 44.4 per 100,000), while 951 (22.0%) were attributable to infections (ASR 41.6 per 100,000). Cancers of the cervix (n = 392, ASR 28.3 per 100,000) and liver (n = 145, ASR 3.4 per 100,000); and non-Hodgkin's lymphoma (n = 110, ASR 2.5 per 100,000) were the commonest infections-associated cancers overall. The commonest infectious agents associated with cancers in this population were HPV, EBV, hepatitis B and C, HIV, and HHV8. CONCLUSION: Our results suggest that 23.8% of incident cancer cases in this population were associated with infections, while 22.0% were attributable to infections. The infections attributable cancers are potentially preventable with strategies, such as vaccination, risk factor modification, or anti-infective treatment.

Recurrence of cervical intraepithelial lesions after thermo-coagulation in HIV-positive and HIV-negative Nigerian women.

BACKGROUND: The burden of cervical cancer remains huge globally, more so in sub-Saharan Africa. Effectiveness of screening, rates of recurrence following treatment and factors driving these in Africans have not been sufficiently studied. The purpose of this study therefore was to investigate factors associated with recurrence of cervical intraepithelial lesions following thermo-coagulation in HIV-positive and HIV-negative Nigerian women using Visual Inspection with Acetic Acid (VIA) or Lugol's Iodine (VILI) for diagnosis. METHODS: A retrospective cohort study was conducted, recruiting participants from the cervical cancer "see and treat" program of IHVN. Data from 6 sites collected over a 4-year period was used. Inclusion criteria were: age ≥18 years, baseline HIV status known, VIA or VILI positive and thermo-coagulation done. Logistic regression was performed to examine the proportion of women with recurrence and to examine factors associated with recurrence. RESULTS: Out of 177 women included in study, 67.8 % (120/177) were HIV-positive and 32.2 % (57/177) were HIV-negative. Recurrence occurred in 16.4 % (29/177) of participants; this was 18.3 % (22/120) in HIV-positive women compared to 12.3 % (7/57) in HIV-negative women but this difference was not statistically significant (p-value 0.31). Women aged ≥30 years were much less likely to develop recurrence, adjusted OR = 0.34 (95 % CI = 0.13, 0.92). Among HIV-positive women, CD4 count <200cells/mm(3) was associated with recurrence, adjusted OR = 5.47 (95 % CI = 1.24, 24.18). CONCLUSION: Recurrence of VIA or VILI positive lesions after thermo-coagulation occurs in a significant proportion of women. HIV-positive women with low CD4 counts are at increased risk of recurrent lesions and may be related to immunosuppression.