Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity

Holmes, E.; Mitra, A.; MacIntyre, D. A.; Lee, Y. S.; Smith, A.; Marchesi, J. R.; Lehne, B.; Bhatia, R.; Lyons, D.; Paraskevaidis, E.; Li, J. V.; Nicholson, J. K.; Bennett, P. R.; Kyrgiou, M.

Abstract

Persistent infection with oncogenic Human Papillomavirus (HPV) is necessary for cervical carcinogenesis. Although evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of HPV infections, this has yet to be described in women with cervical intra-epithelial neoplasia (CIN). We hypothesised that increasing microbiome diversity is associated with increasing CIN severity. llumina MiSeq sequencing of 16S rRNA gene amplicons was used to characterise the vaginal microbiota of women with low-grade squamous intra-epithelial lesions (LSIL; n = 52), high-grade (HSIL; n = 92), invasive cervical cancer (ICC; n = 5) and healthy controls (n = 20). Hierarchical clustering analysis revealed an increased prevalence of microbiomes characterised by high-diversity and low levels of Lactobacillus spp. (community state type-CST IV) with increasing disease severity, irrespective of HPV status (Normal = 2/20,10%; LSIL = 11/52,21%; HSIL = 25/92,27%; ICC = 2/5,40%). Increasing disease severity was associated with decreasing relative abundance of Lactobacillus spp. The vaginal microbiome in HSIL was characterised by higher levels of Sneathia sanguinegens (P < 0.01), Anaerococcus tetradius (P < 0.05) and Peptostreptococcus anaerobius (P < 0.05) and lower levels of Lactobacillus jensenii (P < 0.01) compared to LSIL. Our results suggest advancing CIN disease severity is associated with increasing vaginal microbiota diversity and may be involved in regulating viral persistence and disease progression.

• Journal Article Type: Article
• Acceptance Date: Oct 21, 2015
• Online Publication Date: Nov 17, 2015
• Publication Date: Nov 17, 2015
• Deposit Date: Oct 2, 2019
• Publicly Available Date: Oct 4, 2019
• Journal: Scientific Reports
• Electronic ISSN: 2045-2322
• Publisher: Nature Research (part of Springer Nature)
• Peer Reviewed: Peer Reviewed
• Volume: 5
• Issue: 1
• DOI: https://doi.org/10.1038/srep16865
• Keywords: Multidisciplinary
• Public URL: https://uwe-repository.worktribe.com/output/3454287
• Additional Information: Received: 18 September 2015; Accepted: 21 October 2015; First Online: 17 November 2015; : The authors declare no competing financial interests.