Cervicovaginal microbiome and HPV progression

Results from a longitudinal study suggest that bacteria in the cervicovaginal microbiome (CVM) may play a role in risk of progression of high-risk human papillomavirus (HR-HPV) to cervical precancer.

If the connection is validated in future studies, it could hold promise for development of microbial biomarkers for progression risks of HR-HPV to cervical intraepithelial neoplasia 2 (CIN2).

Published in PLoS Pathogens, the findings are from a nested study within the placebo arm of the Costa Rica HPV Vaccine Trial, which included women aged 18 to 25. The authors looked at the prospective role of the CVM on the natural history of HR-HPV by assessing cervical samples from 273 women with HR-HPV taken during two visits. Their focus was on infection clearance, persistence, and progression to CIN2 and CIN3.

Analysis of the samples from Visit 1 showed that an abundance of Lactobacillus iners was associated with clearance of incident HR-HPV infections (Linear Discriminant Analysis [LDA] > 4.0) whereas Gardnerella was the dominant biomarker for HR-HPV progression (LDA > 4.0). At Visit 2, increased microbial Shannon diversity was significantly associated with progression to CIN2 (P = 0.027).

Multivariate analysis showed that the positive association between Gardnerella and CIN2 progression was a result of the increased cervicovaginal diversity seen in the swabs from Visit 2.

A full multivariate model of key components of the CVM showed significant protective effects via Visit 1 genus Lactobacillus (OR = 0.41 [0.22 to 0.79]), fungal diversity (OR = 0.90 [0.82 to 1.00]) and functional cell motility pathway (OR = 0.75 [0.62 to 0.92]) whereas Visit 2 bacterial diversity (OR = 1.19 [1.03 to 1.38]) was shown to be predictive of progression to CIN2.

The authors said of their data on Gardnerella that “rather than directly causing the CIN2+ lesions, [it] appears to induce a higher diversity CVM over time as measured at V2 which in turn mediates the observed effect of Gardnerella in HR-HPV disease progression.”

Further, “the association may be tied to the ability of Gardnerella to be immunosuppressive in the cervicovaginal region. Whereas, it seems that the presence of commensal bacteria (e.g. Lactobacillus) with the ability to stimulate a local immune response may be contributing factors to the clearance of incident HR-HPV infections.”

Additional prospective studies are needed, the researchers concluded, to establish a causal link between the CVM, the immune system, and the natural history of HPV.

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References:

Usyk M, Zolnik CP, Castle PE, et al. Cervicovaginal microbiome and natural history of HPV in a longitudinal study. PLOS Pathog. 2020;16(3). doi:10.1371/journal.ppat.1008376