HPV vaccination associates with Lactobacillus crispatus-dominant vaginal microbiota in women with cervical lesions: a metagenomic study

Background:

Human papillomavirus (HPV) vaccination provides high-level protection against cervical cancer through type-specific antibodies, although breakthrough and persistent high-risk HPV (hrHPV) infections may still occur in some vaccinated women. In addition to neutralizing antibodies, vaccination elicits other immune mechanisms that may influence viral persistence and disease progression. Because mucosal immunity is closely linked to the vaginal microbiota, microbial composition may also play an important role in HPV susceptibility, with Lactobacillus crispatus dominance associated with protection, and dysbiosis with impaired mucosal immunity. Whether HPV vaccination is associated with favorable microbiota signatures in women with confirmed cervical cancer-related conditions remains unknown.

 

Method:

We analyzed vaginal samples via shotgun metagenomic sequencing from a cross-sectional study of 59 pre-menopausal women (<50 years) with confirmed cervical lesions (HPV-unvaccinated n = 26, vaccinated n = 33).

 

Results:

Alpha diversity (Shannon and Inverse Simpson indices) did not differ significantly by vaccination status, suggesting within-sample microbial diversity between the groups, but Bray-Curtis-based PERMANOVA indicated a statistically significant difference in overall community composition between groups (p = 0.042). Among women with CST I, 90.9% were vaccinated, whereas among women with CST IV, 60.0% were unvaccinated. At the species level, L. crispatus relative abundance was higher in vaccinated women in the unadjusted analysis; however, this association was attenuated and was not statistically significant after multivariable adjustment. HPV vaccination status was associated with a higher prevalence of L. crispatus-dominant, health-associated vaginal microbiota among women with cervical lesions.

 

Conclusion:

These findings support the hypothesis that HPV vaccination status is associated with L. crispatus dominance in this population, but mechanistic pathways remain to be elucidated.

 

 

For more information: Araneta, Ruvie Pearl, et al. "HPV vaccination associates with Lactobacillus crispatus-dominant vaginal microbiota in women with cervical lesions: a metagenomic study." Frontiers in Microbiology 17 (2026): 1906211. DOI: 10.3389/fmicb.2026.1906211