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, Costa Rica HPV Vaccine Trial (CVT) Group, Robert D Burk, Bernal Cortés, Paula González, Silvia E Jiménez, Ana Cecilia Rodríguez, Allan Hildesheim, Aimée R Kreimer, Douglas R Lowy, Mark Schiffman, John T Schiller, Mark Sherman, Sholom Wacholder, Troy J Kemp, Mary K Sidawy, Wim Quint, Leen-Jan van Doorn, Linda Struijk, Joel M Palefsky, Teresa M Darragh, Mark H Stoler, 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, Costa Rica HPV Vaccine Trial (CVT) Group, Robert D Burk, Bernal Cortés, Paula González, Silvia E Jiménez, Ana Cecilia Rodríguez, Allan Hildesheim, Aimée R Kreimer, Douglas R Lowy, Mark Schiffman, John T Schiller, Mark Sherman, Sholom Wacholder, Troy J Kemp, Mary K Sidawy, Wim Quint, Leen-Jan van Doorn, Linda Struijk, Joel M Palefsky, Teresa M Darragh, Mark H Stoler
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.
Conflict of interest statement
The authors declare no competing interests.
© 2022. The Author(s).
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