{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:30:02Z","timestamp":1789777802041,"version":"4.0.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15\/00345"],"award-info":[{"award-number":["PI15\/00345"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/00154"],"award-info":[{"award-number":["PI18\/00154"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Development Regional Fund"},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundaci\u00f3n Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","award":["AC17\/00022"],"award-info":[{"award-number":["AC17\/00022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>While the microbiota has been associated with human papillomavirus malignant transformation, it is unclear whether anal bacteria could improve the low specificity of anal cytology for the screening of high-grade intraepithelial squamous neoplasia (HSIL)<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We recruited men who have sex with men undergoing anal cytology and high-resolution anoscopy. We assessed the microbiota composition from fecal samples and cytobrush anal samples using 16S ribosomal DNA sequencing in participants with or without biopsy-proven HSIL (bHSIL). We selected bacterial biomarkers based on their linear discriminant analysis. We assessed their predictive performance using logistic regression and bootstrap resampling.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We included 128 individuals, 47 (36.7%) with bHSIL and 99 (77.3%) with human immunodeficiency virus. We detected 40 potential predictors of bHSIL. Ruminococcaceae NK4A214 group, Alloprevotella genus, Prevotella melanonigenica, and Ruminococcaceae UCG-014 were the most predictive of bHSIL. From 35 false-positive cytologic results, the combination of these 4 biomarkers with the anal cytology reclassified to true-negative 33 individuals (94%) and showed good diagnostic performance (area under the receiver operating characteristic curve, 0.805; 95% confidence interval, .728\u2013.882).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We found anal-associated bacteria indicative of a higher risk of precancerous anal lesions, which combination was highly specific. The microbiota could be developed as a complementary diagnostic tool to overcome the limitations of the current screening strategy for anal cancer.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiab068","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T05:43:58Z","timestamp":1612331038000},"page":"1247-1256","source":"Crossref","is-referenced-by-count":15,"title":["Exploiting the Microbiota for the Diagnosis of Anal Precancerous Lesions in Men Who Have Sex With Men"],"prefix":"10.1093","volume":"224","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3439-8438","authenticated-orcid":false,"given":"Raquel","family":"Ron","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Hospital Universitario Ramon y Cajal, Facultad de Medicina, Universidad de Alcal\u00e1, IRYCIS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Cabello","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Hospital Universitario Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Gosalbes","sequence":"additional","affiliation":[{"name":"Area of Genomics and Health, FISABIO-Salud P\u00fablica, Valencia, Spain"},{"name":"CIBERESP, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"S\u00e1nchez-Conde","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hospital Universitario Ramon y Cajal, Facultad de Medicina, Universidad de Alcal\u00e1, IRYCIS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Talavera-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Bioinformatics Unit, Hospital Universitario Ramon y Cajal, IRYCIS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Zamora","sequence":"additional","affiliation":[{"name":"CIBERESP, Madrid, Spain"},{"name":"Clinical Biostatistics Unit, Hospital Universitario Ramon y Cajal, IRYCIS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Monge-Maillo","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hospital Universitario Ramon y Cajal, Facultad de Medicina, Universidad de Alcal\u00e1, IRYCIS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hospital Universitario Ramon y Cajal, Facultad de Medicina, Universidad de Alcal\u00e1, IRYCIS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Mart\u00ednez-Sanz","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hospital Universitario Ramon y Cajal, Facultad de Medicina, Universidad de Alcal\u00e1, IRYCIS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Area of Genomics and Health, FISABIO-Salud P\u00fablica, Valencia, Spain"},{"name":"CIBERESP, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Crespillo","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hospital Universitario Ramon y Cajal, Facultad de Medicina, Universidad de Alcal\u00e1, IRYCIS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Velasco","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hospital Universitario Ramon y Cajal, Facultad de Medicina, Universidad de Alcal\u00e1, IRYCIS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hospital Universitario Ramon y Cajal, Facultad de Medicina, Universidad de Alcal\u00e1, IRYCIS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A","family":"P\u00e9rez-Molina","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hospital Universitario Ramon y Cajal, Facultad de Medicina, Universidad de Alcal\u00e1, IRYCIS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Serrano-Villar","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hospital Universitario Ramon y Cajal, Facultad de Medicina, Universidad de Alcal\u00e1, IRYCIS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"2021101318533675800_CIT0001","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1097\/QAD.0000000000002218","article-title":"Incidence and time trends of anal cancer among people living with HIV in Australia","volume":"33","author":"Jin","year":"2019","journal-title":"AIDS"},{"key":"2021101318533675800_CIT0002","first-page":"924","article-title":"International trends in anal cancer incidence rates","volume":"46","author":"Islami","year":"2017","journal-title":"Int J Epidemiol"},{"key":"2021101318533675800_CIT0003","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1200\/JCO.2017.74.9291","article-title":"Anal cancer risk among people with HIV infection in the United States","volume":"36","author":"Col\u00f3n-L\u00f3pez","year":"2018","journal-title":"J Clin Oncol"},{"key":"2021101318533675800_CIT0004","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/s41586-020-2095-1","article-title":"Microbiome analyses of blood and tissues suggest cancer diagnostic approach","volume":"579","author":"Poore","year":"2020","journal-title":"Nature"},{"key":"2021101318533675800_CIT0005","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1126\/science.aal5240","article-title":"Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer","volume":"358","author":"Bullman","year":"2017","journal-title":"Science"},{"key":"2021101318533675800_CIT0006","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1126\/science.aan4236","article-title":"Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients","volume":"359","author":"Gopalakrishnan","year":"2018","journal-title":"Science"},{"key":"2021101318533675800_CIT0007","doi-asserted-by":"crossref","first-page":"e0188851","DOI":"10.1371\/journal.pone.0188851","article-title":"Screening for precancerous anal lesions with P16\/Ki67 immunostaining in HIV-infected MSM","volume":"12","author":"Serrano-Villar","year":"2017","journal-title":"PLoS One"},{"key":"2021101318533675800_CIT0008","doi-asserted-by":"crossref","first-page":"e0163278","DOI":"10.1371\/journal.pone.0163278","article-title":"Incidence of and risk factors for pediatric metachronous contralateral inguinal hernia: analysis of a 17-year nationwide database in Taiwan","volume":"11","author":"Lee","year":"2016","journal-title":"PLoS One"},{"key":"2021101318533675800_CIT0009","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1093\/cid\/ciy970","article-title":"5-Year prospective evaluation of cytology, human papillomavirus testing, and biomarkers for detection of anal precancer in human immunodeficiency virus-positive men who have sex with men","volume":"69","author":"Clarke","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2021101318533675800_CIT0010","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1097\/QAD.0000000000001462","article-title":"The performance of human papillomavirus biomarkers in predicting anal high-grade squamous intraepithelial lesions in gay and bisexual men","volume":"31","author":"Jin","year":"2017","journal-title":"AIDS"},{"key":"2021101318533675800_CIT0011","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1093\/infdis\/jiy463","article-title":"Human papillomavirus genotypes predict progression of anal low-grade squamous intraepithelial lesions","volume":"218","author":"Liu","year":"2018","journal-title":"J Infect Dis"},{"key":"2021101318533675800_CIT0012","doi-asserted-by":"crossref","first-page":"e0153274","DOI":"10.1371\/journal.pone.0153274","article-title":"Cervical microbiome and cytokine profile at various stages of cervical cancer: a pilot study","volume":"11","author":"Audirac-Chalifour","year":"2016","journal-title":"PLoS One"},{"key":"2021101318533675800_CIT0013","doi-asserted-by":"crossref","first-page":"e1008376","DOI":"10.1371\/journal.ppat.1008376","article-title":"Cervicovaginal microbiome and natural history of HPV in a longitudinal study","volume":"16","author":"Usyk","year":"2020","journal-title":"PLoS Pathog"},{"key":"2021101318533675800_CIT0014","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1038\/mi.2016.129","article-title":"Association of HPV infection and clearance with cervicovaginal immunology and the vaginal microbiota","volume":"10","author":"Shannon","year":"2017","journal-title":"Mucosal Immunol"},{"key":"2021101318533675800_CIT0015","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1093\/infdis\/jiw374","article-title":"The cervicovaginal microbiota and its associations with human papillomavirus detection in HIV-infected and HIV-uninfected Women","volume":"214","author":"Reimers","year":"2016","journal-title":"J Infect Dis"},{"key":"2021101318533675800_CIT0016","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/s43018-020-0090-y","article-title":"TNF-shaped microbiota promotes cancer","volume":"1","author":"Trinchieri","year":"2020","journal-title":"Nat Cancer"},{"key":"2021101318533675800_CIT0017","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1080\/19490976.2020.1737487","article-title":"Specific gut microbiome signature predicts the early-stage lung cancer","volume":"11","author":"Zheng","year":"2020","journal-title":"Gut Microbes"},{"key":"2021101318533675800_CIT0018","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1038\/s41467-020-16079-x","article-title":"Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer","volume":"11","author":"Coutzac","year":"2020","journal-title":"Nat Commun"},{"key":"2021101318533675800_CIT0019","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1097\/QAD.0000000000001352","article-title":"HIV, HPV, and microbiota: partners in crime?","volume":"31","author":"Serrano-Villar","year":"2017","journal-title":"AIDS"},{"key":"2021101318533675800_CIT0020","volume-title":"The Bethesda system for reporting cervical cytology: definitions, criteria, and explanatory notes","author":"Darragh","year":"2001","edition":"2"},{"key":"2021101318533675800_CIT0021","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1097\/PGP.0b013e31826916c7","article-title":"The lower anogenital squamous terminology standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology","volume":"32","author":"Darragh","year":"2013","journal-title":"Int J Gynecol Pathol"},{"key":"2021101318533675800_CIT0022","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/nar\/gks808","article-title":"Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies","volume":"41","author":"Klindworth","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2021101318533675800_CIT0023","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: High-resolution sample inference from Illumina amplicon data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat Methods"},{"key":"2021101318533675800_CIT0024","doi-asserted-by":"crossref","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":"2021101318533675800_CIT0025","doi-asserted-by":"crossref","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 Veg Sci"},{"key":"2021101318533675800_CIT0026","doi-asserted-by":"crossref","first-page":"e24704","DOI":"10.1371\/journal.pone.0024704","article-title":"Toward an efficient method of identifying core genes for evolutionary and functional microbial phylogenies","volume":"6","author":"Segata","year":"2011","journal-title":"PLoS One"},{"key":"2021101318533675800_CIT0027","doi-asserted-by":"crossref","first-page":"R60","DOI":"10.1186\/gb-2011-12-6-r60","article-title":"Metagenomic biomarker discovery and explanation","volume":"12","author":"Segata","year":"2011","journal-title":"Genome Biol"},{"key":"2021101318533675800_CIT0028","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1089\/aid.2018.0158","article-title":"Anal microbial patterns and oncogenic human papillomavirus in a pilot study of Nigerian men who have sex with men at risk for or living with HIV","volume":"35","author":"Nowak","year":"2019","journal-title":"AIDS Res Hum Retroviruses"},{"key":"2021101318533675800_CIT0029","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s40168-016-0203-0","article-title":"The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next?","volume":"4","author":"Mitra","year":"2016","journal-title":"Microbiome"},{"key":"2021101318533675800_CIT0030","doi-asserted-by":"crossref","first-page":"10200","DOI":"10.1038\/s41598-017-09842-6","article-title":"Characterization of cervico-vaginal microbiota in women developing persistent high-risk human Papillomavirus infection","volume":"7","author":"Di Paola","year":"2017","journal-title":"Sci Rep"},{"key":"2021101318533675800_CIT0031","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1158\/1940-6207.CAPR-15-0350","article-title":"Cervical microbiota associated with higher grade cervical intraepithelial neoplasia in women infected with high-risk human papillomaviruses","volume":"9","author":"Piyathilake","year":"2016","journal-title":"Cancer Prev Res (Phila)"},{"key":"2021101318533675800_CIT0032","doi-asserted-by":"crossref","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":"2021101318533675800_CIT0033","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1002\/path.5047","article-title":"The microbiome and cancer","volume":"244","author":"Goodman","year":"2018","journal-title":"J Pathol"},{"key":"2021101318533675800_CIT0034","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1097\/COH.0000000000000430","article-title":"The functional consequences of the microbiome in HIV: insights from metabolomic studies","volume":"13","author":"Serrano-Villar","year":"2018","journal-title":"Curr Opin HIV AIDS"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiab068\/36588256\/jiab068.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/224\/7\/1247\/40632134\/jiab068.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/224\/7\/1247\/40632134\/jiab068.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T06:18:56Z","timestamp":1634537936000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/224\/7\/1247\/6129308"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,5]]},"references-count":34,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,2,5]]},"published-print":{"date-parts":[[2021,10,13]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiab068","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,10,1]]},"published":{"date-parts":[[2021,2,5]]}}}