The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea.
Recent studies have suggested potential roles of the microbiome in cervicovaginal diseases. However, there has been no report on the cervical microbiome in cervical intraepithelial neoplasia (CIN). We aimed to identify the cervical microbiota of Korean women and assess the association between the cervical microbiota and CIN, and to determine the combined effect of the microbiota and human papillomavirus (HPV) on the risk of CIN. The cervical microbiota of 70 women with CIN and 50 control women was analysed using pyrosequencing based on the 16S rRNA gene. The associations between specific microbial patterns or abundance of specific microbiota and CIN risk were assessed using multivariate logistic regression, and the relative excess risk due to interaction (RERI) and the synergy index (S) were calculated. The phyla Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, Tenericutes, Fusobacteria and TM7 were predominant in the microbiota and four distinct community types were observed in all women. A high score of the pattern characterized by predominance of Atopobium vaginae, Gardnerella vaginalis and Lactobacillus iners with a minority of Lactobacillus crispatus had a higher CIN risk (OR 5.80, 95% CI 1.73-19.4) and abundance of A. vaginae had a higher CIN risk (OR 6.63, 95% CI 1.61-27.2). The synergistic effect of a high score of this microbial pattern and oncogenic HPV was observed (OR 34.1, 95% CI 4.95-284.5; RERI/S, 15.9/1.93). A predominance of A. vaginae, G. vaginalis and L. iners with a concomitant paucity of L. crispatus in the cervical microbiota was associated with CIN risk, suggesting that bacterial dysbiosis and its combination with oncogenic HPV may be a risk factor for cervical neoplasia.
Division of Cancer Epidemiology and Management, National Cancer Centre, Ilsandong-gu, Goyang, Korea.
H Y
HY
Oh
Chunlab Inc., Seoul National University, Seoul, Korea; Department of Life Science, Hallym University, Chuncheon, Korea.
B-S
BS
Kim
Centre for Uterine Cancer, National Cancer Centre, Ilsandong-gu, Goyang, Korea.
S-S
SS
Seo
Division of Cancer Epidemiology and Management, National Cancer Centre, Ilsandong-gu, Goyang, Korea.
J-S
JS
Kong
Department of Obstetrics and Gynaecology, Korea University College of Medicine, Seoul, Korea.
J-K
JK
Lee
Centre for Uterine Cancer, National Cancer Centre, Ilsandong-gu, Goyang, Korea.
S-Y
SY
Park
Division of Cancer Biology, National Cancer Centre, Goyang-si, Korea.
K-M
KM
Hong
Division of Cancer Biology, National Cancer Centre, Goyang-si, Korea.
H-K
HK
Kim
Division of Cancer Epidemiology and Management, National Cancer Centre, Ilsandong-gu, Goyang, Korea. Electronic address: alrud@ncc.re.kr.
M K
MK
Kim
D000293:Adolescent; D000328:Adult; D000368:Aged; D001419:Bacteria / Q000145:classification* / Q000235:genetics*; D002584:Cervix Uteri / Q000382:microbiology*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004275:DNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D007723:Korea / Q000453:epidemiology; D064307:Microbiota; D008875:Middle Aged; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D018570:Risk Assessment; D017422:Sequence Analysis, DNA; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology*
D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D012336:RNA, Ribosomal, 16S
Atopobium vaginae; Lactobacillus crispatus; Lactobacillus iners; cervical intraepithelial neoplasia; human papillomavirus; microbiome; pyrosequencing