molBV reveals immune landscape of bacterial vaginosis and predicts human papillomavirus infection natural history

Mykhaylo Usyk, Nicolas F. Schlecht, Sarah Pickering, LaShanda Williams, Christopher C. Sollecito, Ana Gradissimo, Carolina Porras, Mahboobeh Safaeian, Ligia Pinto, Rolando Herrero, Howard D. Strickler, Shankar Viswanathan, Anne Nucci-Sack, Angela Diaz and Robert D. Burk ()
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Mykhaylo Usyk: Albert Einstein College of Medicine
Nicolas F. Schlecht: Albert Einstein College of Medicine
Sarah Pickering: Icahn School of Medicine at Mount Sinai
LaShanda Williams: Albert Einstein College of Medicine
Christopher C. Sollecito: Albert Einstein College of Medicine
Ana Gradissimo: Albert Einstein College of Medicine
Carolina Porras: Fundación INCIENSA
Mahboobeh Safaeian: Roche Molecular Diagnostics
Ligia Pinto: Frederick National Laboratory for Cancer Research
Rolando Herrero: Fundación INCIENSA
Howard D. Strickler: Albert Einstein College of Medicine
Shankar Viswanathan: Albert Einstein College of Medicine
Anne Nucci-Sack: Icahn School of Medicine at Mount Sinai
Angela Diaz: Icahn School of Medicine at Mount Sinai
Robert D. Burk: Albert Einstein College of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Bacterial vaginosis (BV) is a highly prevalent condition that is associated with adverse health outcomes. It has been proposed that BV’s role as a pathogenic condition is mediated via bacteria-induced inflammation. However, the complex interplay between vaginal microbes and host immune factors has yet to be clearly elucidated. Here, we develop molBV, a 16 S rRNA gene amplicon-based classification pipeline that generates a molecular score and diagnoses BV with the same accuracy as the current gold standard method (i.e., Nugent score). Using 3 confirmatory cohorts we show that molBV is independent of the 16 S rRNA region and generalizable across populations. We use the score in a cohort without clinical BV states, but with measures of HPV infection history and immune markers, to reveal that BV-associated increases in the IL-1β/IP-10 cytokine ratio directly predicts clearance of incident high-risk HPV infection (HR = 1.86, 95% CI: 1.19-2.9). Furthermore, we identify an alternate inflammatory BV signature characterized by elevated TNF-α/MIP-1β ratio that is prospectively associated with progression of incident infections to CIN2 + (OR = 2.81, 95% CI: 1.62-5.42). Thus, BV is a heterogeneous condition that activates different arms of the immune response, which in turn are independent risk factors for HR-HPV clearance and progression. Clinical Trial registration number: The CVT trial has been registered under: NCT00128661.

Date: 2022
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DOI: 10.1038/s41467-021-27628-3

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