The vaginal microbiome of reproductive-age women is an indicator of cervical human papillomavirus infection
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Data
2020-02-19
Autores
Morales, Julia Andrade Pessoa
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Universidade Estadual Paulista (Unesp)
Resumo
Introdução: O entendimento do papel desempenhado pela microbiota vaginal para a saúde reprodutiva tem ganhado destaque na literatura mundial, especialmente no que se refere à associação com a infecção pelo Papilomavírus Humano (HPV). Diversos fatores de risco para a infecção por HPV já foram identificados, com destaque para a vaginose bacteriana (VB). Apesar de tal associação já ter sido demonstrada, diversos aspectos dessa relação permanecem desconhecidos, dada a diversidade microbiana presente no ambiente vaginal. Embora a recente caracterização do microbioma vaginal tenha permitido o conhecimento da real composição microbiana nesse ambiente, a relação entre componentes do microbioma vaginal e a infecção por HPV permanece por ser elucidada. Objetivo: O objetivo desse estudo é avaliar a associação entre componentes do microbioma vaginal e a infecção cervical por genótipos de alto risco oncogênico do HPV (hrHPV). Pacientes e Métodos: Trata-se de estudo transversal incluindo 546 mulheres oriundas das 5 macrorregiões brasileiras incluídas em estudo prévio intitulado “Caracterização do microbioma vaginal de mulheres brasileiras em idade reprodutiva”. O microbioma vaginal foi determinado pelo sequenciamento das regiões V3-V4 do gene bacteriano RNAr 16S em equipamento MiSeq Plataforma 300PE (Illumina, San Diego, CA) e agrupados em community- state types (CSTs). Amostras cervicais foram submetidas à pequisa e genotipagem de HPV empregando-se o kit Linear Array HPV genotyping (Roche Molecular Systems, Pleasanton, CA). Modelos de regressão logística stepwise (forward, P<0,15) foram utilizados para a construção de dois escores lineares para predizer a positividade para hrHPV: um baseado exclusivamente na presença dos taxons bacterianos identificados (microbiome-based [MB] score) e o outro baseado exclusivamente em características sociodemográficas, comportamentais e clínicas (SBC score). O MB score combinou coeficientes de 30 (de 116) espécies retidas no modelo. O SBC score reteu 6 (idade, estatus marital, nova parceria sexual, uso de contraceptivo hormonal, índice de massa corporal, e tabagismo) de 25 variáveis candidatas. Foram construídas curvas ROC para os escores para a correlação com hrHPV e comparadas suas AUC e 95% IC para inferir a diferença em suas performances de predição. Resultados: A prevalência de hrHPV foi 15,8% (n=86) e 143 (26,2%) participantes tiverem microbioma com depleção de predomínio lactobacilar. As AUC foram 0,8022 (IC: 0.7517-0.8527) para o MB score e 0,7027 (IC: 0.6419-0.7636) para o SBC score (P=0,0163 para a diferença entre AUCs). Conclusão: O estudo demonstra a forte correlação entre 8 componentes do microbioma vaginal e a infecção por hrHPV, propondo a utilidade dos componentes do microbioma como indicador da infecção por hrHPV, aqui demonstrados através do MB score. A utilidade clínica do score como ferramenta preditora da infecção por hrHPV deve ser validada posteriormente em estudos longitudinais.
Background: The understanding of the role played by vaginal microbiome on reproductive health has gained prominence in literature recently, specially regarding to its association to human papillomavirus (HPV) infection. Several risk factors for cervical HPV infection were already identified, highlighting bacterial vaginosis (BV). Despite the association between HPV and BV is well recognized, most aspects of this relation remain unknown. This is in part due to the great heterogeneity present in vaginal environment. Although the recent vaginal microbiome characterization has allowed the understanding of the real microbial composition in that local, the relation between vaginal microbiome components and HPV infection is to be elucidated. Aim: The aim of this study it to evaluate the association between vaginal microbiome components and cervical high-risk HPV (hrHPV) infection. Patients and Methods: We cross-sectionally enrolled 546 women from the five macro-regions of Brazil in previous study entitled “Characterization of the vaginal microbiome in Brazilian women of reproductive-age”. Vaginal microbiome was then determined by sequencing V3-V4 regions of bacterial rRNA 16S gene through MiSeq Platform 300PE (Illumina, San Diego, CA) and clustered in community-state types (CSTs). Cervical samples were subjected to HPV detection and genotyping using Linear Array HPV genotyping kit (Roche Molecular Systems, Pleasanton, CA). We used stepwise (forward, p<0.15) logistic regression to construct two linear scores to predict hrHPV positivity: one based exclusively on the presence of individual bacterial taxa (microbiom-base [MB] score) and the other exclusively on participants’ sociodemographic, behavioral and clinical (SBC) characteristics. The MB score combined coefficients of 30 (out of 116) species retained in the model. The SBC score retained six (age, marital status, new sex partner, hormonal contraceptive use, body mass index and smoking) out of 25 candidate variables. We constructed receiver operating characteristic curves for the scores as hrHPV correlates and compared the areas under the curve (AUC) and 95% confidence intervals (CI) to infer the difference in predictive performance. Results: The prevalence of hrHPV was 15.8% (n=86), and 143 (26.2%) participants had Lactobacillus-depleted vaginal microbiome. The AUCs were 0.8022 (CI: 0.7517-0.8527) for the MB score and 0.7027 (CI: 0.6419-0.7636) for the SBC score (P=0.0163 for the difference between AUCs). Conclusions: Our findings demonstrate the strong correlation between vaginal microbiome components and 10 hrHPV positivity, here demonstrated by MB score, warranting further validation of its clinical utility as a hrHPV infection predictor via longitudinal studies.
Background: The understanding of the role played by vaginal microbiome on reproductive health has gained prominence in literature recently, specially regarding to its association to human papillomavirus (HPV) infection. Several risk factors for cervical HPV infection were already identified, highlighting bacterial vaginosis (BV). Despite the association between HPV and BV is well recognized, most aspects of this relation remain unknown. This is in part due to the great heterogeneity present in vaginal environment. Although the recent vaginal microbiome characterization has allowed the understanding of the real microbial composition in that local, the relation between vaginal microbiome components and HPV infection is to be elucidated. Aim: The aim of this study it to evaluate the association between vaginal microbiome components and cervical high-risk HPV (hrHPV) infection. Patients and Methods: We cross-sectionally enrolled 546 women from the five macro-regions of Brazil in previous study entitled “Characterization of the vaginal microbiome in Brazilian women of reproductive-age”. Vaginal microbiome was then determined by sequencing V3-V4 regions of bacterial rRNA 16S gene through MiSeq Platform 300PE (Illumina, San Diego, CA) and clustered in community-state types (CSTs). Cervical samples were subjected to HPV detection and genotyping using Linear Array HPV genotyping kit (Roche Molecular Systems, Pleasanton, CA). We used stepwise (forward, p<0.15) logistic regression to construct two linear scores to predict hrHPV positivity: one based exclusively on the presence of individual bacterial taxa (microbiom-base [MB] score) and the other exclusively on participants’ sociodemographic, behavioral and clinical (SBC) characteristics. The MB score combined coefficients of 30 (out of 116) species retained in the model. The SBC score retained six (age, marital status, new sex partner, hormonal contraceptive use, body mass index and smoking) out of 25 candidate variables. We constructed receiver operating characteristic curves for the scores as hrHPV correlates and compared the areas under the curve (AUC) and 95% confidence intervals (CI) to infer the difference in predictive performance. Results: The prevalence of hrHPV was 15.8% (n=86), and 143 (26.2%) participants had Lactobacillus-depleted vaginal microbiome. The AUCs were 0.8022 (CI: 0.7517-0.8527) for the MB score and 0.7027 (CI: 0.6419-0.7636) for the SBC score (P=0.0163 for the difference between AUCs). Conclusions: Our findings demonstrate the strong correlation between vaginal microbiome components and 10 hrHPV positivity, here demonstrated by MB score, warranting further validation of its clinical utility as a hrHPV infection predictor via longitudinal studies.
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Palavras-chave
Papillomaviridae, Microbiota, Aparelho genital feminino