{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:11:37Z","timestamp":1787026297854,"version":"build-2736575974"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Microbiota-relevant signatures have been investigated for human papillomavirus-related cervical cancer (CC), but lack consistency because of study- and methodology-derived heterogeneities. Here, four publicly available 16S rRNA datasets including 171 vaginal samples (51 CC versus 120 healthy controls) were analyzed to characterize reproducible CC-associated microbial signatures. We employed a recently published clustering approach called VAginaL community state typE Nearest CentroId clAssifier to assign the metadata to 13 community state types (CSTs) in our study. Nine subCSTs were identified. A random forest model (RFM) classifier was constructed to identify 33 optimal genus-based and 94 species-based signatures. Confounder analysis revealed confounding effects on both study- and hypervariable region-associated aspects. After adjusting for confounders, multivariate analysis identified 14 significantly changed taxa in CC versus the controls (\n                    <jats:italic>P<\/jats:italic>\n                    &amp;lt; 0.05). Furthermore, predicted functional analysis revealed significantly upregulated pathways relevant to the altered vaginal microbiota in CC. Cofactor, carrier, and vitamin biosynthesis were significantly enriched in CC, followed by fatty acid and lipid biosynthesis, and fermentation of short-chain fatty acids. Genus-based contributors to the differential functional abundances were also displayed. Overall, this integrative study identified reproducible and generalizable signatures in CC, suggesting the causal role of specific taxa in CC pathogenesis.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2023.1024723","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T02:32:08Z","timestamp":1674095528000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Leveraging 16S rRNA data to uncover vaginal microbial signatures in women with cervical cancer"],"prefix":"10.3389","volume":"13","author":[{"given":"Ming","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueqian","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanrong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengting","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyi","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalan","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangqin","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jintian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cha","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxia","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random forests","volume":"45","author":"Breiman","year":"2001","journal-title":"Mach. learning."},{"key":"B3","first-page":"3","article-title":"Manual on setting up, using, and understanding random forests v3. 1","volume":"1","author":"Breiman","year":"2002","journal-title":"Stat Department Univ. California Berkeley CA U.S.A."},{"key":"B4","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.ajog.2018.12.011","article-title":"Vaginal dysbiosis and the risk of human papillomavirus and cervical cancer: systematic review and meta-analysis","volume":"221","author":"Brusselaers","year":"2019","journal-title":"Am. J. Obstet Gynecol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"D471","DOI":"10.1093\/nar\/gkv1164","article-title":"The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway\/genome databases","volume":"44","author":"Caspi","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1016\/j.jiph.2020.05.024","article-title":"The correlation between the determination of vaginal micro-ecological composition and the outcome of HPV infection by high-throughput metagene sequencing information technology on the illumina platform","volume":"13","author":"Cheng","year":"2020","journal-title":"J. Infect. Public Health"},{"key":"B7","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1186\/s12879-020-05324-9","article-title":"Human papillomavirus infection and cervical intraepithelial neoplasia progression are associated with increased vaginal microbiome diversity in a Chinese cohort","volume":"20","author":"Chen","year":"2020","journal-title":"BMC Infect. Dis."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00487-20","article-title":"The complex link between the female genital microbiota, genital infections, and inflammation","volume":"89","author":"Dabee","year":"2021","journal-title":"Infect. Immun."},{"key":"B9","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1111\/j.1654-1103.2003.tb02228.x","article-title":"VEGAN, a package of r functions for community ecology","volume":"14","author":"Dixon","year":"2003","journal-title":"J. Vegetation Science."},{"key":"B10","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/s41587-020-0548-6","article-title":"PICRUSt2 for prediction of metagenome functions","volume":"38","author":"Douglas","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1038\/s41419-021-04388-y","article-title":"Lactobacillus spp. create a protective micro-ecological environment through regulating the core fucosylation of vaginal epithelial cells against cervical cancer","volume":"12","author":"Fan","year":"2021","journal-title":"Cell Death Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1038\/s41564-022-01083-2","article-title":"Towards a deeper understanding of the vaginal microbiota","volume":"7","author":"France","year":"2022","journal-title":"Nat. Microbiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1186\/s40168-020-00934-6","article-title":"VALENCIA: A nearest centroid classification method for vaginal microbial communities based on composition","volume":"8","author":"France","year":"2020","journal-title":"Microbiome"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00162-20","article-title":"Identification of a cytopathogenic toxin from sneathia amnii","volume":"202","author":"Gentile","year":"2020","journal-title":"J. Bacteriol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.ebiom.2019.04.028","article-title":"Deciphering the complex interplay between microbiota, HPV, inflammation and cancer through cervicovaginal metabolic profiling","volume":"44","author":"Ilhan","year":"2019","journal-title":"EBioMedicine"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.615439","article-title":"Influence of pelvic intensity-modulated radiation therapy with concurrent cisplatin-based chemotherapy of cervical cancer on the vaginal microbiome","volume":"11","author":"Jiang","year":"2021","journal-title":"Front. Oncol."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9020294","article-title":"Potential association between vaginal microbiota and cervical carcinogenesis in Korean women: A cohort study","volume":"9","author":"Kang","year":"2021","journal-title":"Microorganisms"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1128\/JCM.00854-08","article-title":"Heterogeneity of vaginal microbial communities within individuals","volume":"47","author":"Kim","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1007\/s00203-019-01747-4","article-title":"Cervical cancer and vaginal microbiota changes","volume":"202","author":"Kovachev","year":"2020","journal-title":"Arch. Microbiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1084\/jem.172.1.77","article-title":"Lipid IVA inhibits synthesis and release of tumor necrosis factor induced by lipopolysaccharide in human whole blood ex vivo","volume":"172","author":"Kovach","year":"1990","journal-title":"J. Exp. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"7593","DOI":"10.1038\/s41598-018-25879-7","article-title":"Linking cervicovaginal immune signatures, HPV and microbiota composition in cervical carcinogenesis in non-Hispanic and Hispanic women","volume":"8","author":"Laniewski","year":"2018","journal-title":"Sci. Rep."},{"key":"B22","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41522-021-00259-8","article-title":"Bacterial vaginosis and health-associated bacteria modulate the immunometabolic landscape in 3D model of human cervix","volume":"7","author":"Laniewski","year":"2021","journal-title":"NPJ Biofilms Microbiomes."},{"key":"B23","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/s41585-020-0286-z","article-title":"The microbiome and gynaecological cancer development, prevention and therapy","volume":"17","author":"\u0141aniewski","year":"2020","journal-title":"Nat. Rev. Urology."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics10121013","article-title":"Vaginal microbiome-based bacterial signatures for predicting the severity of cervical intraepithelial neoplasia","volume":"10","author":"Lee","year":"2020","journal-title":"Diagnostics (Basel)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.645951","article-title":"Leveraging 16S rRNA microbiome sequencing data to identify bacterial signatures for irritable bowel syndrome","volume":"11","author":"Liu","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s40168-016-0222-x","article-title":"Gut microbiota dysbiosis contributes to the development of hypertension","volume":"5","author":"Li","year":"2017","journal-title":"Microbiome"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.838491","article-title":"Preliminary identification of the aerobic cervicovaginal microbiota in Mexican women with cervical cancer as the first step towards metagenomic studies","volume":"12","author":"Manzanares-Leal","year":"2022","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"16865","DOI":"10.1038\/srep16865","article-title":"Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity","volume":"5","author":"Mitra","year":"2015","journal-title":"Sci. Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1186\/s13073-021-00977-w","article-title":"The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia","volume":"13","author":"Mitra","year":"2021","journal-title":"Genome Med."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12040350","article-title":"Reprogramming of fatty acid metabolism in gynaecological cancers: Is there a role for oestradiol","volume":"12","author":"Mozihim","year":"2022","journal-title":"Metabolites"},{"key":"B31","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1021\/acs.jproteome.0c00640","article-title":"Comparable plasma lipid changes in patients with high-grade cervical intraepithelial neoplasia and patients with cervical cancer","volume":"20","author":"Nam","year":"2021","journal-title":"J. Proteome Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"976024","DOI":"10.1155\/2010\/976024","article-title":"Pattern recognition via the toll-like receptor system in the human female genital tract","volume":"2010","author":"Nasu","year":"2010","journal-title":"Mediators Inflamm."},{"key":"B33","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1111\/1471-0528.15854","article-title":"The vaginal microbiota, human papillomavirus and cervical dysplasia: A systematic review and network meta-analysis","volume":"127","author":"Norenhag","year":"2020","journal-title":"BJOG"},{"key":"B34","doi-asserted-by":"publisher","first-page":"D590","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA ribosomal RNA gene database project: Improved data processing and web-based tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"4680","DOI":"10.1073\/pnas.1002611107","article-title":"Vaginal microbiome of reproductive-age women","volume":"108","author":"Ravel","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B36","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/1471-2105-12-77","article-title":"pROC: An open-source package for r and s+ to analyze and compare ROC curves","volume":"12","author":"Robin","year":"2011","journal-title":"BMC Bioinf."},{"key":"B37","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.trecan.2021.10.008","article-title":"Redrawing therapeutic boundaries: microbiota and cancer","volume":"8","author":"Sholl","year":"2022","journal-title":"Trends Cancer."},{"key":"B38","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"B39","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1080\/1040841X.2021.1905606","article-title":"Sneathia: An emerging pathogen in female reproductive disease and adverse perinatal outcomes","volume":"47","author":"Theis","year":"2021","journal-title":"Crit. Rev. Microbiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/s41591-019-0405-7","article-title":"Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation","volume":"25","author":"Thomas","year":"2019","journal-title":"Nat. Med."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.680038","article-title":"Changes in the vaginal microbiome and associated toxicities following radiation therapy for gynecologic cancers","volume":"11","author":"Tsementzi","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"5261","DOI":"10.1128\/AEM.00062-07","article-title":"Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy","volume":"73","author":"Wang","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2534","DOI":"10.1093\/bioinformatics\/bts485","article-title":"An r package suite for microarray meta-analysis in quality control, differentially expressed gene analysis and pathway enrichment detection","volume":"28","author":"Wang","year":"2012","journal-title":"Bioinformatics"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1007\/s00248-021-01800-0","article-title":"The diversity of vaginal microbiota predicts neoadjuvant chemotherapy responsiveness in locally advanced cervical cancer","volume":"84","author":"Wang","year":"2021","journal-title":"Microb. Ecol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2748","DOI":"10.1038\/s41396-020-0727-y","article-title":"Multi-omic meta-analysis identifies functional signatures of airway microbiome in chronic obstructive pulmonary disease","volume":"14","author":"Wang","year":"2020","journal-title":"ISME J."},{"key":"B46","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/s41591-019-0406-6","article-title":"Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer","volume":"25","author":"Wirbel","year":"2019","journal-title":"Nat. Med."},{"key":"B47","doi-asserted-by":"publisher","first-page":"3063","DOI":"10.1038\/s41467-021-23265-y","article-title":"Identification of microbial markers across populations in early detection of colorectal cancer","volume":"12","author":"Wu","year":"2021","journal-title":"Nat. Commun."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.538336","article-title":"Revealing the disturbed vaginal micobiota caused by cervical cancer using high-throughput sequencing technology","volume":"10","author":"Xie","year":"2020","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1111\/j.1365-2958.2006.05406.x","article-title":"The group b streptococcus NADH oxidase nox-2 is involved in fatty acid biosynthesis during aerobic growth and contributes to virulence","volume":"62","author":"Yamamoto","year":"2006","journal-title":"Mol. Microbiol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"6757","DOI":"10.1038\/s41467-021-27112-y","article-title":"Dysbiosis of human gut microbiome in young-onset colorectal cancer","volume":"12","author":"Yang","year":"2021","journal-title":"Nat. Commun."},{"key":"B51","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.canlet.2018.09.006","article-title":"Dietary oleic acid-induced CD36 promotes cervical cancer cell growth and metastasis via up-regulation Src\/ERK pathway","volume":"438","author":"Yang","year":"2018","journal-title":"Cancer Lett."},{"key":"B52","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s12866-021-02152-y","article-title":"Distinction between vaginal and cervical microbiota in high-risk human papilloma virus-infected women in China","volume":"21","author":"Zhang","year":"2021","journal-title":"BMC Microbiol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"568","DOI":"10.7150\/jca.29072","article-title":"A randomised trial of probiotics to reduce severity of physiological and microbial disorders induced by partial gastrectomy for patients with gastric cancer","volume":"10","author":"Zheng","year":"2019","journal-title":"J. Cancer."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1024723\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T02:32:13Z","timestamp":1674095533000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1024723\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,19]]},"references-count":53,"alternative-id":["10.3389\/fcimb.2023.1024723"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2023.1024723","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,19]]},"article-number":"1024723"}}