ena-STUDY-CUSB-HM-17-11-2014-13:53:00:303-1131
Characterization of the vaginal microbiome in women with cervical intraepithelial neoplasia
Background: The healthy vaginal microbiota is typically Lactobacillus spp. dominant and it plays an important role in the prevention of urogenital diseases and infections. Persistent infection with oncogenic HPV subtypes is necessary for the development of invasive cervical cancer. Recent evidence indicates that the vaginal microbiome may play a functional role in the persistence or regression of Human Papillomavirus (HPV) infections. The vaginal microbiome in women with cervical intra-epithelial neoplasia (CIN) has yet to be investigated.  Objectives: To characterize the vaginal microbiome structure and diversity in women with different CIN grades.  Material and Methods:  Population: Reproductive age, non-pregnant women of reproductive age with CIN attending the colposcopy clinic. Setting: Imperial College Healthcare NHS Trust. Interventions: Vaginal swabs were collected from the posterior vaginal fornix and bacterial DNA extracted. The vaginal microbiome was characterised by 16S rRNA gene sequencing using an Illumina MiSeq platform. Women were categorized in to two groups on the basis of histology and cytology; women with low-grade (LSIL) and high-grade squamous intra-epithelial lesions (HSIL). Analysis: Supervised, and unsupervised multivariate modeling of sequence data was used to examine bacterial species classification data, and correlated these to the disease severity. Richness and diversity indices were calculated for patient population groups.   Results: We analysed 39 women with CIN, which were divided in to LSIL (n=11) and HSIL (n=28) grades. Hierarchical clustering analysis of bacterial species data revealed 3 distinct community state types (CST I: Lactobacillus crispatus; CST III: Lactobacillus iners; CST IV: mixed diverse Lactobacillus-depleted microbiome) in women with CIN. 26% of our predominantly Caucasian population had a high-diversity, non-Lactobacillus dominated microbiome (CST IV), which is approximately 3 times greater than the rate documented for Caucasian women without CIN in previous reports. None of the women with CIN had a Lactobacillus gasseri-dominated (CST II). The proportion of women with CST IV vaginal microbiome was similar for women with LSIL (n=3 out of 11; 27%) versus women with HSIL (8 out of 28; 28%).  Conclusions: One third of women with CIN have a more diverse Lactobacillus-depleted vaginal microbiome, higher than the rates previously reported in normal populations. This high rate of microbiome diversity may reflect lesions that are likely to progress and warrants further investigation. A Lactobacillus gasseri-dominated microbiome was not observed in this population of women with CIN. This supports previous reports indicating that Lactobacillus gasseri is correlated with rapid HPV clearance. Future therapeutic strategies may allow modulation of the vaginal microbiome toward a vaginal community structure that promotes HPV clearance.
Background: The healthy vaginal microbiota is typically Lactobacillus spp. dominant and it plays an important role in the prevention of urogenital diseases and infections. Persistent infection with oncogenic HPV subtypes is necessary for the development of invasive cervical cancer. Recent evidence indicates that the vaginal microbiome may play a functional role in the persistence or regression of Human Papillomavirus (HPV) infections. The vaginal microbiome in women with cervical intra-epithelial neoplasia (CIN) has yet to be investigated.  Objectives: To characterize the vaginal microbiome structure and diversity in women with different CIN grades.  Material and Methods:  Population: Reproductive age, non-pregnant women of reproductive age with CIN attending the colposcopy clinic. Setting: Imperial College Healthcare NHS Trust. Interventions: Vaginal swabs were collected from the posterior vaginal fornix and bacterial DNA extracted. The vaginal microbiome was characterised by 16S rRNA gene sequencing using an Illumina MiSeq platform. Women were categorized in to two groups on the basis of histology and cytology; women with low-grade (LSIL) and high-grade squamous intra-epithelial lesions (HSIL). Analysis: Supervised, and unsupervised multivariate modeling of sequence data was used to examine bacterial species classification data, and correlated these to the disease severity. Richness and diversity indices were calculated for patient population groups.   Results: We analysed 39 women with CIN, which were divided in to LSIL (n=11) and HSIL (n=28) grades. Hierarchical clustering analysis of bacterial species data revealed 3 distinct community state types (CST I: Lactobacillus crispatus; CST III: Lactobacillus iners; CST IV: mixed diverse Lactobacillus-depleted microbiome) in women with CIN. 26% of our predominantly Caucasian population had a high-diversity, non-Lactobacillus dominated microbiome (CST IV), which is approximately 3 times greater than the rate documented for Caucasian women without CIN in previous reports. None of the women with CIN had a Lactobacillus gasseri-dominated (CST II). The proportion of women with CST IV vaginal microbiome was similar for women with LSIL (n=3 out of 11; 27%) versus women with HSIL (8 out of 28; 28%).  Conclusions: One third of women with CIN have a more diverse Lactobacillus-depleted vaginal microbiome, higher than the rates previously reported in normal populations. This high rate of microbiome diversity may reflect lesions that are likely to progress and warrants further investigation. A Lactobacillus gasseri-dominated microbiome was not observed in this population of women with CIN. This supports previous reports indicating that Lactobacillus gasseri is correlated with rapid HPV clearance. Future therapeutic strategies may allow modulation of the vaginal microbiome toward a vaginal community structure that promotes HPV clearance.