Prevotella as the hub of the cervicovaginal microbiota affects the occurrence of persistent human papillomavirus infection and cervical lesions in women of childbearing age via host NF-κB/C-myc

J Med Virol. 2022 Nov;94(11):5519-5534. doi: 10.1002/jmv.28001. Epub 2022 Jul 30.

Abstract

There is evidence that coinfection of cervicovaginal high-risk human papillomavirus (HR-HPV) and bacteria is common in women of childbearing age. However, the relationship between bacterial vaginosis (BV) and persistent HR-HPV infection in women of childbearing age and the underlying mechanisms remain unclear. In this study, we determined whether BV affects persistent HR-HPV infection in women aged 20-45 years and explored the possible mechanisms of their interactions. From January 1 to April 30, 2020, we recruited women aged 20-45 years with and without BV at a ratio of 1:2 from Fujian Maternity and Child Health Hospital. All women were followed up at 0, 12, and 24 months. A BV assay, HR-HPV genotyping and cervical cytology were performed at each follow-up. At 0 months, additional vaginal secretions and cervical exfoliated cells were collected for 16S ribosomal RNA sequencing, bacterial metabolite determination, and POU5F1B, C-myc, TLR4, NF-κB, and hTERT quantification. A total of 920 women were included. The abundance of Prevotella (p = 0.016) and Gardnerella (p = 0.027) were higher, whereas the abundance of Lactobacillus was lower (p = 0.001) in women with persistent HR-HPV infection and high-grade squamous intraepithelial lesions (HSIL). The abundance of Prevotella (p = 0.025) and Gardnerella (p = 0.018) increased in the vaginas of women with persistent HPV16 infection, whereas only the abundance of Prevotella (p = 0.026) was increased in women with persistent HPV18 infection. The abundance of Prevotella in the vagina was significantly positively correlated with the expression levels of TLR4, NF-κB, C-myc, and hTERT in host cervical cells (p < 0.05). Our findings suggest that overgrowth of Prevotella in the vagina may influence the occurrence of persistent HR-HPV infection-related cervical lesions through host NF-κB and C-myc signaling.

Keywords: C-myc; NF-κB; Prevotella; cervicovaginal microbiota; human papillomavirus; persistent infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Female
  • Humans
  • Microbiota*
  • NF-kappa B / metabolism
  • Papillomaviridae / genetics
  • Papillomavirus Infections*
  • Pregnancy
  • Prevotella / genetics
  • Prevotella / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • Signal Transduction
  • Toll-Like Receptor 4
  • Uterine Cervical Dysplasia*
  • Uterine Cervical Neoplasms*

Substances

  • NF-kappa B
  • Proto-Oncogene Proteins c-myc
  • Toll-Like Receptor 4