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P34 Cervical intraepithelial neoplasia is associated with an altered vaginal microbiome and innate immune disruption
  1. A Mitra1,
  2. D Macintyre1,
  3. Y Lee1,
  4. A Smith2,
  5. J Marchesi1,2,
  6. D Lyons3,
  7. S Stock4,
  8. P Bennett1 and
  9. M Kyrgiou1
  1. 1Imperial College London, London, UK
  2. 2Cardiff University, Cardiff
  3. 3Imperial College NHS Healthcare Trust, London, UK
  4. 4Edinburgh University, Edinburgh, UK


Introduction/Background The innate immune system is a key factor in the fate of an HPV infection and a proinflammatory environment has been shown to facilitate HPV persistence and cervical carcinogenesis. Antimicrobial peptides (AMPs) have innate antibacterial and antiviral properties, as well as a role in tissue remodelling but have not been studied in cervical intraepithelial neoplasia (CIN). Bacterial vaginosis is known to be associated with HPV infection and CIN, therefore the vaginal microbiota (VMB) may also influence the innate immune response and subsequent disease state.

We aimed to investigate changes in VMB composition and expression of Human Beta Defensin-1 (hBD-1), Secretory Leucocyte Protease Inhibitor (SLPI) and inflammatory cytokines according to disease status.

Methodology Population: Non-pregnant, premenopausal women attending the colposcopy clinic in London, UK with cytological ± histological disease classification.

Analysis: Vaginal swab samples were used for 16s rRNA bacterial sequencing to assess VMB composition and for enzyme-linked immunosorbent assay (ELISA) to determine hBD-1, SLPI, IL-1b and IL-8 levels.

Results A total of 232 women were included and classified into three groups; 34 normal, 81 low-grade CIN, and 117 high-grade CIN. Lower levels of Lactobacillus spp. with increased bacterial species diversity, were seen with increasing disease severity. A bacterial vaginosis-like VMB was observed twice as frequently in women with high-grade disease (28%) compared to controls (14%). Higher levels of pro-inflammatory cytokines; IL-1b and IL-8 and AMPs; hBD-1 and SLPI increase with increasing disease severity.

Conclusion Lactobacillus spp. are thought to protect the female reproductive tract from pathogens, including viruses and the lower levels observed with increasing disease severity, along with higher levels of pro-inflammatory cytokines may play a role in disease outcomes. AMPs are known to be overexpressed in several cancers, and therefore higher levels may have a deleterious effect due their ability to facilitate tissue remodeling that is required for carcinogenesis.

Disclosure Nothing to disclose.

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