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

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

Conclusion

Although alpha diversity was similar between HR Normal, dysplasia and cancer patients, composition differed significantly between the three groups. Increased anorectal

Informations de copyright

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.

Déclaration de conflit d'intérêts

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.