Exploiting the microbiota for the diagnosis of anal precancerous lesions in men who have sex with men

Raquel Ron, Alfonso Cabello, María José Gosalbes, Matilde Sánchez-Conde, Alba Talavera-Rodríguez, Javier Zamora, Begoña Monge-Maillo, Daniel Jiménez, Javier Martínez-Sanz, Yolanda López, Clara Crespillo, Tamara Velasco, Santiago Moreno, José A. Pérez-Molina, Sergio Serrano-Villar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1247-1256
Number of pages10
JournalJournal of Infectious Diseases
Issue number7
Early online date5 Feb 2021
Publication statusPublished - 1 Oct 2021

Bibliographical note

Funding Information:
This work was supported by the Instituto de Salud Carlos III (Plan Estatal de I+D+i 2013-2016; projects PI15/00345, PI18/00154), the European Development Regional Fund ("A way to achieve Europe"), and investigation was also funded by the Instituto de Salud Carlos III and the Fundación Asociación Española Contra el Cáncer within the ERANET TRANSCAN-2 program (grant AC17/00022).

Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.


  • anal cancer
  • dysplasia
  • HIV
  • HPV
  • microbiota

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases


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