Nov 17, 2015 - Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity. A. Mitra1,2, D. A. MacIntyre1, ...
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received: 18 September 2015 accepted: 21 October 2015 Published: 17 November 2015
Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity A. Mitra1,2, D. A. MacIntyre1, Y. S. Lee1, A. Smith3, J. R. Marchesi3,4, B. Lehne5, R. Bhatia6, D. Lyons7, E. Paraskevaidis8, J. V. Li4, E. Holmes4, J. K. Nicholson4, P. R. Bennett1,2 & M. Kyrgiou1,2 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
