Microbiome may hold key to identifying HPV-infected women at risk for pre-cancer

March 26, 2020

Gardnerella bacteria in the cervicovaginal microbiome may serve as a biomarker to identify women infected with human papillomavirus (HPV) who are at risk for progression to precancer, according to a study published March 26 in the open-access journal PLOS Pathogens by Robert Burk and Mykhaylo Usyk of the Albert Einstein College of Medicine, and colleagues. According to the authors, the findings could lead to therapeutic strategies that manipulate the microbiome to prevent disease progression.

HPV infection is one of the most common sexually transmitted infections and the causal agent of cervical cancer. But it is still not clear why only a small proportion of high-risk HPV infections progress to cervical cancer. To investigate the potential role of the cervicovaginal microbiome, Burk, Usyk and their collaborators evaluated cervical samples from 273 women who had high-risk HPV infection and were participating in the Costa Rica HPV Vaccine Trial.

They found that the abundance of Lactobacillus iners was associated with clearance of high-risk HPV infections. By contrast, Gardnerella bacteria were the dominant biomarker for progression of a high-risk HPV. Additional analyses revealed that the effect of Gardnerella is mediated by increased cervicovaginal bacterial diversity directly preceding the progression of a persistent infection to precancer. The findings suggest that monitoring the presence of Gardnerella and the subsequent elevation in microbial diversity could be used to identify women with persistent high-risk HPV infection at risk for progression to precancer. If future studies support a causal role of the cervicovaginal microbiome and disease progression, then it might be possible to manipulate the cervicovaginal microbiome in a manner to activate a local immune response and prevent disease progression.

The authors add, "The investigators prospectively demonstrate that progression of a persistent high-risk HPV infection to cervical precancer is in part explained by unique features of the cervicovaginal microbiota."
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Research Article

Funding: The Costa Rica HPV Vaccine Trial is a long-standing collaboration between investigators in Costa Rica and the NCI. The trial is sponsored and funded by the NCI (contract N01-CP-11005), with funding support from the National Institutes of Health Office of Research on Women's Health. GlaxoSmithKline Biologicals (GSK) provided vaccine and support for aspects of the trial associated with regulatory submission needs of the company under a Clinical Trials Agreement (FDA BB-IND 7920) during the four-year, randomized blinded phase of our study. MU, RDB, CPZ and AG were funded by the National Cancer Institute (NCI) (U01 CA78527). The original Costa Rica vaccine trial was sponsored and funded by the NCI (contract N01-CP-11005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: I have read the journal's policy and have the following conflicts: John T. Schiller and Douglas R. Lowy report that they are named inventors on US Government-owned HPV vaccine patents that are licensed to GlaxoSmithKline and Merck and for which the National Cancer Institute receives licensing fees. They are entitled to limited royalties as specified by federal law.

Citation: Usyk M, Zolnik CP, Castle PE, Porras C, Herrero R, Gradissimo A, et al. (2020) Cervicovaginal microbiome and natural history of HPV in a longitudinal study. PLoS Pathog 16(3): e1008376. https://doi.org/10.1371/journal.ppat.1008376

Author Affiliations:

Department of Pediatrics (Genetic Medicine), Albert Einstein College of Medicine, Bronx, New York, United States of America

Department of Epidemiology and Population Health, NYU School of Medicine, New York, New York, United States of America

Department of Biology, Long Island University, Brooklyn, New York, United States of America

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, United States of America

Agencia Costarricense de Investigaciones Biomédicas (ACIB), formerly Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, San José, Costa Rica

Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, France

Roche Molecular Diagnostics, Pleasanton, California, United States of America

Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute, NIH, Bethesda, Maryland, United States of America

Departments of Microbiology and Immunology, and Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, New York, United States of America

PLOS

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