Cervicovaginal microbiome and natural history of HPV in a longitudinal study

Area of Science:

• Microbiology
• Gynecology
• Infectious Diseases

Background:

• Human papillomavirus (HPV) is a common sexually transmitted infection.
• Only a fraction of high-risk HPV infections lead to cervical precancer or cancer.
• The cervicovaginal microbiome's role in HR-HPV natural history requires further investigation.

Purpose of the Study:

• To investigate the cervicovaginal microbiome's role in the natural history of high-risk HPV infections.
• To determine if CVM composition predicts HR-HPV clearance, persistence, or progression to CIN2+.
• To explore potential therapeutic targets within the CVM for preventing cervical cancer.

Main Methods:

• Prospective longitudinal study nested within the Costa Rica HPV Vaccine Trial (n=273).
• Cervical samples analyzed for bacterial (16S rRNA) and fungal (ITS1) DNA using Illumina MiSeq.
• OTU clustering, functional imputation (PICRUSt), and statistical analyses (R, LDA) performed.

Main Results:

• Lactobacillus iners at Visit 1 associated with HR-HPV clearance; Gardnerella at Visit 1 associated with progression.
• Increased cervicovaginal microbial diversity at Visit 2 linked to progression to CIN2+.
• Gardnerella-CIN2+ association mediated by increased cervicovaginal diversity; Lactobacillus and fungal diversity showed protective effects.

Conclusions:

• Cervicovaginal microbiome features prospectively associate with HR-HPV progression.
• Microbial diversity may mediate the link between Gardnerella and CIN2+ progression.
• Specific CVM components offer potential targets for therapeutic interventions against CIN2+.