Authors

Jacob H. Elnaggar, LSU Health Sciences Center - New OrleansFollow
Victoria O. Huynh, LSU Health Sciences Center - New OrleansFollow
Daniel Lin, University of Texas MD Anderson Cancer Center
R. Tyler Hillman, University of Texas MD Anderson Cancer Center
Chike O. Abana, University of Texas MD Anderson Cancer Center
Molly B. El Alam, University of Texas MD Anderson Cancer Center
Katarina C. Tomasic, University of Texas MD Anderson Cancer Center
Tatiana V. Karpinets, University of Texas MD Anderson Cancer Center
Ramez Kouzy, University of Texas MD Anderson Cancer Center
Jae L. Phan, University of Texas MD Anderson Cancer Center
Jennifer Wargo, University of Texas MD Anderson Cancer Center
Emma B. Holliday, University of Texas MD Anderson Cancer Center
Prajnan Das, University of Texas MD Anderson Cancer Center
Melissa P. Mezzari, Baylor College of Medicine
Nadim J. Ajami, University of Texas MD Anderson Cancer Center
Erica J. Lynn, University of Texas MD Anderson Cancer Center
Bruce D. Minsky, University of Texas MD Anderson Cancer Center
Van K. Morris, University of Texas MD Anderson Cancer Center
Andrea Milbourne, University of Texas MD Anderson Cancer Center
Craig A. Messick, University of Texas MD Anderson Cancer Center
Ann H. Klopp, University of Texas MD Anderson Cancer Center
P. Andrew Futreal, University of Texas MD Anderson Cancer Center
Cullen M. Taniguchi, University of Texas MD Anderson Cancer Center
Kathleen M. Schmeler, University of Texas MD Anderson Cancer Center
Lauren E. Colbert, University of Texas MD Anderson Cancer Center

Document Type

Article

Publication Date

3-29-2023

Publication Title

Frontiers in Immunology

Abstract

Background: Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease. Methods: Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade lower genital tract dysplasia. Anorectal tumor swabs were prospectively collected from patients with biopsy-confirmed locally advanced SCCA prior to receiving standard-of-care chemoradiotherapy (CRT). Patients with high-grade lower genital tract dysplasia without anal dysplasia were considered high-risk (HR Normal). 16S V4 rRNA Microbiome sequencing was performed for anal swabs. Alpha and Beta Diversity and composition were compared for HR Normal, anal dysplasia, and anal cancer. Results: 60 patients with high-grade lower genital tract dysplasia were initially enrolled. Seven patients had concurrent anal dysplasia and 44 patients were considered HR Normal. Anorectal swabs from 21 patients with localized SCCA were included, sequenced, and analyzed in the study. Analysis of weighted and unweighted UniFrac distances demonstrated significant differences in microbial community composition between anal cancer and HR normal (p=0.018). LEfSe identified that all three groups exhibited differential enrichment of specific taxa. Peptoniphilus (p=0.028), Fusobacteria (p=0.0295), Porphyromonas (p=0.034), and Prevotella (p=0.029) were enriched in anal cancer specimens when compared to HR normal. Conclusion: Although alpha diversity was similar between HR Normal, dysplasia and cancer patients, composition differed significantly between the three groups. Increased anorectal Peptoniphilus, Fusobacteria, Porphyromonas, and Prevotella abundance were associated with anal cancer. These organisms have been reported in various gastrointestinal cancers with roles in facilitating the proinflammatory microenvironment and neoplasia progression. Future work should investigate a potential role of microbiome analysis in screening for anal dysplasia and investigation into potential mechanisms of how these microbial imbalances influence the immune system and anal carcinogenesis.

PubMed ID

37063829

Volume

14

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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