Disparities in the Epidemiology of Anal Cancer: A Cross-Sectional Time Series

Oliveira, Carlos Rocha; Niu, Yu Si; Einarsdóttir, Hildur; Niccolai, Linda M.; Shapiro, Eugene D.

doi:10.1089/heq.2020.0021

Cited by 5 publications

(3 citation statements)

References 16 publications

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“…However, 30-40% of patients with advanced SCCA experience local recurrence or treatment-related toxicity ( 4 , 5 ). Despite the use of HPV vaccines, the incidence and morbidity of SCCA continue to rise ( 6 ). Anal dysplasia is poorly understood and has been more difficult to detect than lower genital tract dysplasia.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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BackgroundSquamous 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.MethodsPatients 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.Results60 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.ConclusionAlthough 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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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“…[3][4][5][6][7] Despite the use of HPV vaccines, the incidence and morbidity from SCCA continue to rise. 8 The human microbiome influences the onset and treatment response of many malignancies, including gastrointestinal cancers, [9][10][11] through the modulation of inflammation, cell proliferation, and metabolism. 12,13 Clinical and preclinical data suggest that gut microbiota can directly and indirectly modulate therapy response and toxicity.…”

Section: Introductionmentioning

confidence: 99%

Microbiome Dynamics During Chemoradiation Therapy for Anal Cancer

Lin

Alam

Jaoude

et al. 2022

International Journal of Radiation Oncology*Biology*Physics

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“…[3][4][5][6][7] Despite the use of HPV vaccines, the incidence and morbidity from SCCA continue to rise. 8 The human microbiome influences the oncogenesis and treatment response of many cancers, including gastrointestinal cancers, [9][10][11] through the modulation of inflammation, cell proliferation, and metabolism. 12,13 Clinical and preclinical data suggest that gut microbiota are direct modulators of therapy response and toxicity.…”

Section: Introductionmentioning

confidence: 99%

Microbiome Dynamics During Chemoradiotherapy for Anal Cancer

Lin

Alam

Jaoude

et al. 2021

Preprint

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IMPORTANCE: Patients with localized squamous cell carcinoma of the anus (SCCA) who experience treatment toxicity or recurrences have few therapeutic options. Investigation into the microbiome's influence on treatment toxicity or its potential use as a predictive biomarker in this rare disease could improve these patients' outcomes. OBJECTIVE: To longitudinally characterize the SCCA tumor microbiome and assess its association with treatment-related toxicities. DESIGN: Prospective cohort study. SETTING: Single tertiary cancer center. PARTICIPANTS: Twenty-two patients with biopsy-confirmed non-metastatic SCCA receiving standard-of-care chemoradiotherapy as part of an Institutional Review Board-approved study from April 2017 to July 2019. MAIN OUTCOMES AND MEASURES: Diversity and taxonomic characterization of the SCCA microbiome throughout chemoradiotherapy using swab-based anorectal microbial specimen collection and 16S rRNA gene sequencing. RESULTS: Twenty-two SCCA patients were included in this study with a median (range) age of 58.5 (39-77), and 18 (82%) were women. Alpha diversity remained relatively stable throughout chemoradiotherapy, except for decreases in the Chao1 (P=0.03) and Observed Features (P=0.03) indices at week 5 relative to baseline. Tumor microbial compositions measured using weighted UniFrac changed significantly by the end of treatment (P=0.03). Linear discriminant analysis effect sizes revealed differential enrichment of bacteria at specific time points, including the enrichment of Clostridia at both baseline and follow-up and the enrichment of Corynebacterium at week 5. Patients experiencing high toxicity at week 5 had higher relative abundances of Clostridia, Actinobacteria, and Clostridiales at baseline (P=0.03 for all). CONCLUSIONS AND RELEVANCE: Our study presents the first longitudinal characterization of the SCCA microbiome throughout chemoradiation. The tumor microbiome undergoes significant changes during and after chemoradiotherapy, and patient-reported toxicity levels are associated with patients' microbial profiles. Further studies into these microbial characterizations and associations are needed to elucidate the tumor microbiome's role in predicting treatment-related outcomes for SCCA patients.

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Disparities in the Epidemiology of Anal Cancer: A Cross-Sectional Time Series

Cited by 5 publications

References 16 publications

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

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

Microbiome Dynamics During Chemoradiation Therapy for Anal Cancer

Microbiome Dynamics During Chemoradiotherapy for Anal Cancer

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