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.
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.
Persistent high-risk HPV infection is a necessary cause of cervical cancer. HPV DNA testing is now the primary WHO recommended approach to cervical cancer screening. Cervical cancer screening uptake ...remains abysmally low in Nigeria and in other low and middle income countries (LMIC). Antenatal care-based HPV DNA testing is a largely unexplored strategy to increase uptake of cervical cancer screening in LMIC. Up to 70% of women in Africa attend ANC at least once during their pregnancy and many attend at least twice. We evaluated the acceptability of HPV DNA testing as part of routine antenatal care among pregnant women and healthcare workers in Nigeria. We conducted focus group discussions (FGD) among pregnant women and Key Informant Interviews among healthcare providers at a hospital facility in Abuja, Nigeria. A total of 24 muslim and christian pregnant women were invited for the focus groups and each group comprised of 6-10 participants. Obstetric/Gynaecologists (O&G) and ANC nurses were interviewed. We used content analysis method for data analysis. Coding sheets were developed to summarize findings. Our study showed fair level of knowledge and awareness of cervical cancer and cervical cancer screening among the pregnant women, however, practice was poor, as none of the women had ever been screened for cervical cancer. Lack of awareness about cervical cancer screening, costs, and fear of screening outcome were commonly cited as barriers to uptake. The nurses interviewed expressed reservations about the willingness of pregnant women to participate in screening but there was a high level of willingness among the pregnant women to be screened during the ANC period. Their religion and parity played no role in determining the acceptance of HPV DNA testing in ANC. The O&G specialists expressed full support for integrating HPV DNA testing into routine ANC services. Our results show the need to explore more innovative public health interventions to reduce cervical cancer burden in LMIC.
Cervical cancer is the second commonest cancer in Africa. Much remains unknown about the prevalence and pathogenicity of human papilloma virus (HPV) types, mechanism of disease and there is a need ...for new biomarkers for screening programs. ACCME is a multicenter prospective cohort study of host germline, somatic and HPV genomics and epigenomics, and vaginal microenvironment; and their association with cervical cancer in 10,000 HIV negative women in Nigeria. Data on demography, lifestyle, medical history, serum, germline DNA, HPV genotype and vaginal pH are collected at baseline and during follow- up visits every 6 months. Samples of exfoliated cervical cells are analyzed for high-risk HPV with Roche LINEAR ARRAY and vaginal bacterial composition and abundance are characterized by deep sequencing of barcoded 16S rRNA gene fragments (V4) on Illumina MiSeq platform. Colposcopy and biopsy are conducted on participants with clinical lesions and those with persistent high risk HPV infections. By July 2015, ~8500 participants had been enrolled unto the cohort. The mean (SD) age of the study participants at baseline was 40 (10) years. Most of the participants were married (76%), attended university (44%) and had professional jobs (37%). All the study participants have had vaginal sex, 17% have had oral sex and only 2% have ever had anal sex. We found 30% of the study participants were HPV positive and 70% were HPV negative. The mean (SD) vaginal pH in the study population was 5.2 (0.5). Further analyses to characterize high-risk HPV types and determine persistence are ongoing. Also, characterization of cervical cytokines and vaginal microbiome are underway. ACCME is a paradigm for translational research in biomarker discovery that addresses high impact public health challenges affecting women's health in Africa and the rest of the world.
Persistent infection with high risk HPV is associated with increased risk of cervical cancer. Therefore understanding the predictors of persistence may provide some insights in characterizing ...infections that may have clinical significance. From August 2012 to December 2013, we recruited women at our cervical cancer screening clinics in Abuja. Nurses collected ecto-cervical samples for HPV determination which was performed using Roche Linear Array (for 278 baseline samples) and SPF10 DEIA, LiPA25 version 1 for all other samples. Relative risks were estimated using Poisson regression models with robust error variance. Of the 1020 women enrolled, (aged 18-61 years), 727 (71.1%) returned for follow up after mean (SD) 8.6 (4.0) months. Some 42.4% (432/1020) of the participants were HIV positive. Baseline prevalence of any HPV infection was 41.2% (401/973) and of these, 256 women returned for follow-up. Some 62.1% (159/256) remained persistently positive for any HPV. The RR (95% CI, P-value) for an association with prevalent any HPV were 0.99 (0.98 to 0.99, 0.02) for age, 1.23 (1.12 to 1.35, <0.001) for HIV infection, 1.26 (0.97 to 1.63, 0.08) for presence of other STIs, and 1.59 (1.28 to 1.99, <0.001) for abnormal VIA results. The RR (95% CI, P-value) for persistent infection with any HPV were 1.67 (1.39 to 2.01, <0.001) for HIV infection and 2.26 (1.64 to 3.11, <0.001) for abnormal baseline VIA. This preliminary data suggest a high level of persistence of any HPV infection among women with prevalent any HPV infection. Significant predictors of persistence included HIV infection and an abnormal VIA result at baseline. Updated analysis, by HPV genotype, will be available in September.
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