SS 09-04The vaginal microbiota after excisional treatment for cervical intraepithelial neoplasia

17. Microbiome
A. Mitra 1, D. Macintyre 1, Y. Lee 1, S. Lever 1, A. Smith 2, J. Marchesi 3, D. Lyons 4, P. Bennett 1, M. Kyrgiou 1.
1Imperial College London (United Kingdom), 2Cardiff University (United Kingdom), 3Cardiff University/Imperial College London (United Kingdom), 4Imperial College Healthcare NHS Trust (United Kingdom)

Background / Objectives

Background: The vaginal microbiota (VMB) is usually Lactobacillus spp. dominant appears to protect the female reproductive tract against infections including HPV. CST (community state type) III and the high-diversity VMB deplete of Lactobacillus spp. CST IV have both been associated with higher rates of HPV acquisition, persistence and increased severity of cervical intraepithelial neoplasia (CIN). These CST’s have also been associated with pre-term birth (PTB); a known complication of excisional treatment. Furthermore women with a history of treatment are at a higher risk of future invasive cervical disease, which could also be linked to VMB composition.

Objectives: To investigate the impact of excisional treatment for CIN on VMB composition.


Methods

Material and Methods:

Population: Non-pregnant, premenopausal women attending the colposcopy clinic for excisional treatment of histologically-proven CIN in London, UK.

Interventions: Vaginal swabs collected immediately prior to treatment, and at 6 month follow-up. Bacterial DNA was extracted and sequened using the Illumina MiSeq platform.

Analysis: Heirarchical clustering of sequence data was used to examine bacterial species classification data, and linear discriminant analysis effect size (LEfSe) to identify biomarkers. 


Results

One hundred and three women provided both pre- and post-treatment samples. Excisional treatment did not significantly alter the distribution of CSTs within the cohort, and diversity remained significantly greater compared to normal, healthy untreated controls. There was no association with post-treatment CST and HPV status. LEfSe identified Streptococcus agalactiae (Group B streptococcus) to be significantly overrepresented in post-treatment samples. 


Conclusion

Excisional treatment does not appear to have a significant impact on VMB composition. CST III and IV remained at a higher prevalence than in a normal control population. These results suggest that the increased prevalence CST III and IV in women with CIN may be due to intrinsic host factors rather than as a result of disease, and these intrinsic factors may also predispose them to PTB and risk of disease recurrence. Furthermore, Streptococcus agalactiae which has been associated with PTB risk, may add to the risk in this patient cohort. 


References

Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity. Mitra A, MacIntyre DA, Lee YS, Smith A, Marchesi JR, Lehne B, Bhatia R, Lyons D, Paraskevaidis E, Li JV, Holmes E, Nicholson JK, Bennett PR, Kyrgiou M. Sci Rep. 2015 Nov 17;5:16865. 

Effect of ageing on cervical or vaginal cancer in Swedish women previously treated for cervical intraepithelial neoplasia grade 3: population based cohort study of long-term incidence and mortality. Strander B, Hällgren J, Sparén P. BMJ. 2014 Jan 14;348:f7361.