Ayotunde Famooto

Prevalent high-risk HPV infection and vaginal microbiota in Nigerian women.

SUMMARY In this study, we evaluated the association between high-risk human papillomavirus (hrHPV) and the vaginal microbiome. Participants were recruited in Nigeria between April and August 2012. Vaginal bacterial composition was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V4) on Illumina MiSeq and HPV was identified using the Roche Linear Array® HPV genotyping test. We used exact logistic regression models to evaluate the association between community state types (CSTs) of vaginal microbiota and hrHPV infection, weighted UniFrac distances to compare the vaginal microbiota of individuals with prevalent hrHPV to those without prevalent hrHPV infection, and the Linear Discriminant Analysis effect size (LEfSe) algorithm to characterize bacteria associated with prevalent hrHPV infection. We observed four CSTs: CST IV-B with a low relative abundance of Lactobacillus spp. in 50% of participants; CST III (dominated by L. iners) in 39·2%; CST I (dominated by L. crispatus) in 7·9%; and CST VI (dominated by proteobacteria) in 2·9% of participants. LEfSe analysis suggested an association between prevalent hrHPV infection and a decreased abundance of Lactobacillus sp. with increased abundance of anaerobes particularly of the genera Prevotella and Leptotrichia in HIV-negative women (P < 0·05). These results are hypothesis generating and further studies are required.

HIV associated high-risk HPV infection among Nigerian women

BackgroundIn developed countries, the incidence of cervical cancer has remained stable in HIV+ women but the prevalence and multiplicity of high-risk HPV (hrHPV) infection, a necessary cause of cervical cancer, appears different comparing HIV+ to HIV- women. Little is known about HIV and HPV co-infection in Africa.MethodsWe enrolled women presenting at our cervical cancer screening program in Abuja, Nigeria between April and August 2012, and collected information on demographic characteristics, risk factors of HPV infection and samples of exfoliated cervical cells. We used Roche Linear Array HPV Genotyping Test® to characterize prevalent HPV and logistic regression models to estimate the association between HIV and the risk of hrHPV infection.ResultsThere were 278 participants, 54% (151) were HIV+, 40% (111) were HIV-, and 6% (16) had unknown HIV status. Of these, data from 149 HIV+ and 108 HIV- women were available for analysis. The mean ages (±SD) were 37.6 (±7.7) years for HIV+ and 36.6 (±7.9) years for HIV- women (p-value = 0.34). Among the HIV+ women, HPV35 (8.7%) and HPV56 (7.4%) were the most prevalent hrHPV, while HPV52 and HPV68 (2.8%, each) were the most prevalent hrHPV types among HIV- women. The multivariate prevalence ratio for any hrHPV and multiple hrHPV infections were 4.18 (95% CI 2.05 – 8.49, p-value <0.0001) and 6.6 (95% CI 1.49 – 29.64, p-value 0.01) respectively, comparing HIV + to HIV- women, adjusted for age, and educational level.ConclusionsHIV infection was associated with increased risk of any HPV, hrHPV and multiple HPV infections. Oncogenic HPV types 35, 52, 56 and 68 may be more important risk factors for cervical pre-cancer and cancer among women in Africa. Polyvalent hrHPV vaccines meant for African populations should protect against other hrHPV types, in addition to 16 and 18.

Mycoplasma hominis and Mycoplasma genitalium in the Vaginal Microbiota and Persistent High-Risk Human Papillomavirus Infection

Background Recent studies have suggested that the vaginal microenvironment plays a role in persistence of high-risk human papillomavirus (hrHPV) infection and thus cervical carcinogenesis. Furthermore, it has been shown that some mycoplasmas are efficient methylators and may facilitate carcinogenesis through methylation of hrHPV and cervical somatic cells. We examined associations between prevalence and persistence of Mycoplasma spp. in the vaginal microbiota, and prevalent as well as persistent hrHPV infections. Methods We examined 194 Nigerian women who were tested for hrHPV infection using SPF25/LiPA10 and we identified Mycoplasma genitalium and Mycoplasma hominis in their vaginal microbiota established by sequencing the V3–V4 hypervariable regions of the 16S rRNA gene. We defined the prevalence of M. genitalium, M. hominis, and hrHPV based on positive result of baseline tests, while persistence was defined as positive results from two consecutive tests. We used exact logistic regression models to estimate associations between Mycoplasma spp. and hrHPV infections. Results The mean (SD) age of the study participants was 38 (8) years, 71% were HIV positive, 30% M. genitalium positive, 45% M. hominis positive, and 40% hrHPV positive at baseline. At follow-up, 16% of the women remained positive for M. genitalium, 30% for M. hominis, and 31% for hrHPV. There was a significant association between persistent M. hominis and persistent hrHPV (OR 8.78, 95% CI 1.49–51.6, p 0.01). Women who were positive for HIV and had persistent M. hominis had threefold increase in the odds of having persistent hrHPV infection (OR 3.28, 95% CI 1.31–8.74, p 0.008), compared to women who were negative for both. Conclusion We found significant association between persistent M. hominis in the vaginal microbiota and persistent hrHPV in this study, but we could not rule out reverse causation. Our findings need to be replicated in larger, longitudinal studies and if confirmed, could have important diagnostic and therapeutic implications.

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.

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.

Incidence, Persistence, and Determinants of Human Papillomavirus: A Prospective Cohort Study of HIV-Negative Nigerian Women

Abstract 63Background:Cervical cancer is the second most common cancer in Africa. Persistent high-risk human papillomavirus (HRHPV) infection is a necessary cause but little is known about the persistence and associated risk factors of HRHPV infection in African women. We undertook this work to determine risk factors and the 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 in the cohort and are being observed every 6 months. We used SPF25/LiPA10 to characterize HPV infection and defined persistent infection as two consecutive positive tests performed at least 12 months apart. Logistic regression models were used to estimate associations between risk factors and persistent HPV.Results:The mean (± standard deviation) age of study participants at baseline...

Cohort Profile: African Collaborative Center for Microbiome and Genomics Research’s (ACCME's) Human Papillomavirus (HPV) and Cervical Cancer Study

Cohort Profile: African Collaborative Center for Microbiome and Genomics Research’s (ACCME’s) Human Papillomavirus (HPV) and Cervical Cancer Study Sally N Adebamowo,* Eileen O Dareng, Ayotunde O Famooto, Richard Offiong, Olayinka Olaniyan, Kayode Obende, Amos Adebayo, Sanni Ologun, Bunmi Alabi, Peter Achara, Rasheed A Bakare, Michael Odutola, Oluwatoyosi Olawande, James Okuma, George Odonye, Ruxton Adebiyi, Patrick Dakum and Clement A Adebamowo,; ACCME Research Group as part of the H3Africa Consortium

Cohort Profile: African Collaborative Center for Microbiome and Genomics Research (ACCME)

Abstract 65Background:Cervical cancer is the second most common cancer in Africa. Much remains unknown about the prevalence and pathogenicity of human papillomavirus (HPV) types and the mechanism of disease, and there is a need for new biomarkers for screening programs.Methods: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 demographic, 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 a Illumina MiSeq platform. Colposcopies and biopsies are conducted on participants with clinical lesions and those with persistent...

Risk, Persistence and Multiplicity of HPV Infections among HIV Negative and HIV Positive Nigerian Women

Abstract 64Background:The incidence, prevalence, persistence, and multiplicity of high-risk HPV infection is different between HIV positive and HIV negative women. We examined the association between HIV, prevalent HPV, and persistent HPV infections among women in a prospective cohort in Nigeria.Methods:We enrolled women presenting at cervical cancer screening programs in Abuja, Nigeria, between 2012 and 2014 and collected information on their demographic characteristics, risk factors of HPV infection, and cervical exfoliated cells samples at baseline, 6 month and 12 month follow-up visits. DNA enzyme immunoassay (DEIA) and Roche Linear Array HPV Genotyping Test were used to characterize HPV. Persistent HPV infection was defined as a positive result on 2 consecutive DEIA tests. We used logistic regression models to estimate the association between HIV and risk of HPV infection.Results:Among the 1,020 women enrolled, the mean age (±SD) was 37(8), and 44% and 56% were HIV+ and HIV-, respectively. HPV52 and ...

P-B17 Persistent human papillomavirus infection in a cohort of Nigerian women

Objectives: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. Methods: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. Results: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. Conclusions: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.