HPV-related anal cancer is associated with changes in the anorectal microbiome during cancer development.

Autor:	Elnaggar JH; School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, United States.; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Huynh VO; School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, United States., Lin D; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Hillman RT; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.; Cancer Prevention Research Institute of Texas Scholar in Cancer Research, Austin, TX, United States., Abana CO; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., El Alam MB; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Tomasic KC; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Karpinets TV; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Kouzy R; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Phan JL; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Wargo J; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Holliday EB; Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Das P; Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Mezzari MP; The Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States., Ajami NJ; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Lynn EJ; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Minsky BD; Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Morris VK; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Milbourne A; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Messick CA; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Klopp AH; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Futreal PA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Taniguchi CM; Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Schmeler KM; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Colbert LE; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Mar 29; Vol. 14, pp. 1051431. Date of Electronic Publication: 2023 Mar 29 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1051431
Abstrakt:	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. Competing Interests: CT is on the clinical advisory board of Accuracy, has a patent for oral amifostine as a radioprotectant of the upper gastrointestinal tract issued, licensed, and with royalties paid from Xerient Pharmaceuticals and a pending patent for prolyl hydroxylase inhibitors as a radioprotectant of the gastrointestinal tract, was the lead principal investigator of a multicenter trial testing the effects of high-dose stereotactic body radiation therapy with the radiomodulator, GC4419, and is a paid consultant for Phebra Pty, Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Elnaggar, Huynh, Lin, Hillman, Abana, El Alam, Tomasic, Karpinets, Kouzy, Phan, Wargo, Holliday, Das, Mezzari, Ajami, Lynn, Minsky, Morris, Milbourne, Messick, Klopp, Futreal, Taniguchi, Schmeler and Colbert.)
Databáze:	MEDLINE
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