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.
Uptake into cervical cancer screening programs in developing countries is poor. We explored prevailing beliefs and attitudes towards cervical cancer among two religious groups in Nigeria. We ...conducted 4 focus group discussions (FGDs) among Muslim and Christian women. Discussions were conducted in 2 hospitals, one in the South West and the other in the North Central region of Nigeria. Data analysis was done using a combination of deductive and inductive processes using Atlas.ti version 7.5. Results were obtained using the query tools and Boolean operators to interrogate the codes. Most participants in the FGDs had heard about cervical cancer except Muslim women in the South Western Nigeria focus group who had never heard about cervical cancer. Participants believed that wizardry, multiple sexual partners and inserting herbs into the vagina cause cervical cancer. Only one participant knew about the Human Papillomavirus. Among the Christian women, majority of respondents had heard about cervical cancer screening and believed that it could be used to prevent cervical cancer. Participants mentioned religious and cultural obligations of modesty, gender of healthcare providers, fear of disclosure of results, fear of nosocomial infections, lack of awareness, discrimination at hospitals and need for spousal approval as barriers to uptake of screening. These barriers varied by religion across the geographical regions. Barriers to cervical cancer screening vary by religious affiliations. Interventions to increase cervical cancer awareness and screening uptake in multi-cultural and multi-religious communities need to take into consideration the varying cultural and religious beliefs in order to design and implement effective intervention programs.
HPV are the commonest STIs and are the causative agents for genital warts. In this study, we determine the prevalence and incidence of genital warts, its risk factors and the HPV types associated ...with it in HIV+ and HIV- women. We recruited 852 women attending cervical cancer screening clinics in Nigeria between April 2012 and August 2013 and collected information on demographics and behavioral characteristics. Nurses conducted pelvic examinations and performed Visual Inspection with Acetic Acid/Lugol's Iodine. HPV testing was done on cervical exfoliated cells using Roche Linear Array Genotyping Kit. Logistic regression models were used to identify risk factors. The point prevalence of genital warts at baseline was 2.7% (23/852). The baseline prevalence rates were significantly higher among HIV+ women (5.2%, 19/363) than HIV- women (0.8%, 4/489) (OR 6.70, 95% CI: 2.19 to 27.3, P = 0.0001). Risk factors for prevalent genital warts were HIV infection, abnormal cervical morphology on VIA/VILI and inconsistent use of condoms during sexual intercourse. Baseline HPV genotyping result is available on 278 participants of whom 9 (3.2%) had prevalent genital warts. hrHPV was detected in 5 participants, of whom 2 had multiple hrHPV infection. lrHPV was detected in 5 participants with multiple lrHPV infection in 4. Of the 5 individuals infected with hrHPV, 4 were co-infected with lrHPV. Among 239 women followed up over 6 months (contributing 1598 person months), incidence rate of genital warts was 3,003 cases per 100 000 person years (95% CI: 2,897 to 3,112). There was no association between incident genital warts and HIV status in this study (Incident risk ratio 3.23, 95% CI: 0.34 to 30.7, P = 0.28) Genital warts are common among the population sampled. Several participants with genital warts had multiple low risk and high risk HPV infections. Given that genital warts are risk factors for ano-genital malignancies, further research is needed to guide policies on effective prevention and control of genital warts.
Though persistent high risk HPV infection is a necessary cause for cervical cancer, there are few studies in African populations. We previously reported the point prevalence of hrHPV infection to be ...25% among HIV+ and HIV- women attending cervical cancer screening in Nigeria. Here we report on persistence of hrHPV infections in this population. One thousand participants presenting at our cervical cancer screening program were enrolled between April and August 2013 and are being followed up. We present results for 278 women who had HPV testing at baseline and returned for a scheduled follow up visit. Demographics and risk factor information was collected using questionnaires. Roche Linear Array HPV Genotyping Test was used to determine HPV infection from ectocervical cell samples collected at baseline and follow up visits. The duration between first and second HPV testing was 10.5 +/- 5.4 (mean +/-SD) months. Of the 68 participants who had hrHPV at baseline, 49 were re-tested and 10% (5/49) had persistent infection. Of these, 60% (3/5) had type specific persistence (same genotypes present at baseline were present at follow up) and 40% (2/5) had group specific persistence. All participants (5/5) with persistent hrHPV infection were HIV+. Testing of additional participants' samples are continuing and updated results will be presented at the conference. Although this study is limited by the sample size, hrHPV persistence rates in the population sampled is similar to that reported from other populations. Further studies on larger populations are required to elucidate the risk factors of persistent high risk HPV infection among Nigerian women.
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Background: Cervical cancer is the second commonest cancer in Africa. Persistent High-risk HPV (HRHPV) infection is a necessary cause but little is known about the persistence and ...associated risk factors of HRHPV infection in African women. The aim of this study was to determine risk factors and incidence of HPV infection in Nigerian women. Methods: ACCME is a multicenter prospective cohort study of host germline, cervical somatic and HRHPV genomics, epigenomics, and vaginal microenvironment; and their association with HPV. From February/2014 to January/2016, 10,000 HIV-negative women were enrolled into the cohort and are being followed up every 6 months. We used SPF
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/LiPA
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to characterize HPV infection and defined persistent infection as 2 consecutive positive tests done at least 12 months apart. Logistic regression models were used to estimate the associations between risk factors and persistent HPV. Results: The mean (SD) age of the study participants at baseline was 40 (10) years and the mean (SD) vaginal pH was 5.2 (0.6). About 42% of the participants were positive for any HPV positive and 21% had persistence of any HPV infections. Some, 35% of the participants had multiple infections with any HPV. About 54% of those with persistent any HPV infections had HRHPV; HPV types 52 (25%) and 18 (15%) were the most prevalent and persistent HRHPV types. The incidence of any HPV infection was 6.6/1,000 person-months while that of HRHPV was 2.6/1,000 person-months. Age, body mass index, level of education, marital and socio-economic status and total number of lifetime sexual partners were associated with HPV infection in these women. Conclusions: We defined the incidence, risk factors and commonest types of HRHPV in a large cohort of women in West Africa.
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.
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.
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).
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.
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