title: Cervical Microbiota Associated with Higher Grade Cervical Intraepithelial Neoplasia in Women Infected with High-Risk Human Papillomaviruses.
abstract: It is increasingly recognized that microbes that reside in and on human body sites play major roles in modifying the pathogenesis of several diseases, including cancer. However, specific microbes or microbial communities that can be mechanistically linked to cervical carcinogenesis remain largely unexplored. The purpose of the study was to examine the association between cervical microbiota and high-grade cervical intraepithelial neoplasia (CIN 2+) in women infected with high-risk (HR) human papillomaviruses (HPV) and to assess whether the cervical microbiota are associated with oxidative DNA damage as indicated by the presence of cervical cells positive for 8-hydroxy-2'-deoxyguanosine. The study included 340 women diagnosed with CIN 2+ (cases) and 90 diagnosed with CIN 1 (non-cases). Microbiota composition was determined by Illumina sequencing of the 16S rRNA gene amplified from DNA extracted from cervical mucus samples. Measures of alpha/beta-diversity were not associated with either CIN severity or oxidative DNA damage. However, a cervical mucosal community type (CT) dominated by L. iners and unclassified Lactobacillus spp was associated with CIN 2+ (OR = 3.48; 95% CI, 1.27-9.55). Sequence reads mapping to Lactobacillaceae, Lactobacillus, L. reuteri, and several sub-genus level Lactobacillus operational taxonomic units were also associated with CIN 2+ when examined independently (effect size >2.0; P < 0.05). Our 16S rRNA sequencing results need confirmation in independent studies using whole-genome shotgun sequencing and that would allow sharpening the suggested associations at finer taxonomic levels. Our results provide little evidence that DNA oxidative damage mediates the effect of the microbiome on the natural history of HPV infection and CIN severity. Cancer Prev Res; 9(5); 357-66. ©2016 AACR.
authors.affiliation: Department of Nutrition Sciences, The University of Alabama at Birmingham (UAB), Birmingham, Alabama. piyathic@uab.edu.
authors.forename: Chandrika J
authors.initials: CJ
authors.lastname: Piyathilake
authors.affiliation: Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Ollberding
authors.affiliation: University of Alabama at Birmingham (UAB) Center for Clinical & Translational Science.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Macaluso
authors.affiliation: Department of Obstetrics and Gynecology, UAB, Birmingham, Alabama.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Alvarez
authors.affiliation: Department of Cell Developmental and Integrative Biology, UAB, Birmingham, Alabama.
authors.forename: Casey D
authors.initials: CD
authors.lastname: Morrow
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D002584:Cervix Uteri / Q000382:microbiology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005260:Female; D006801:Humans; D064307:Microbiota; D008875:Middle Aged; D060787:Neoplasm Grading; D018384:Oxidative Stress; D030361:Papillomavirus Infections / Q000150:complications; D016133:Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000382:microbiology* / Q000473:pathology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000382:microbiology* / Q000473:pathology*
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine