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Exploiting the Microbiota for the Diagnosis of Anal Precancerous Lesions in Men Who Have Sex With Men

Abstract Background 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) Methods We recruited men w...

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Bibliographic Details
Published in:The Journal of infectious diseases 2021-10, Vol.224 (7), p.1247-1256
Main Authors: Ron, Raquel, Cabello, Alfonso, Gosalbes, María José, Sánchez-Conde, Matilde, Talavera-Rodríguez, Alba, Zamora, Javier, Monge-Maillo, Begoña, Jiménez, Daniel, Martínez-Sanz, Javier, López, Yolanda, Crespillo, Clara, Velasco, Tamara, Moreno, Santiago, Pérez-Molina, José A, Serrano-Villar, Sergio
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Language:English
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Summary:Abstract Background 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) Methods 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. Results 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–.882). Conclusions 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. We here propose a set of bacterial biomarkers indicative of a higher risk of precancerous anal lesions, which combination was highly specific. Our findings indicate that the microbiota could be developed as a complementary diagnostic tool for anal cancer screening.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiab068