Circulating Biomarkers in Localized Anal Squamous Cell Carcinoma Across Treatment Timepoints: A Systematic Review

Area of Science:

• Oncology
• Biomarkers
• Molecular Diagnostics

Background:

• Locoregional anal squamous cell carcinoma (ASCC) treatment can lead to relapse or metastasis.
• Current surveillance methods lack sensitivity and specificity for individualized risk assessment.
• Human papillomavirus (HPV), particularly HPV16, drives most ASCC cases.

Purpose of the Study:

• To systematically review evidence on circulating biomarkers (CBs) for monitoring localized ASCC.
• To evaluate CB performance across different treatment timepoints.
• To assess the potential of CBs in guiding patient follow-up and treatment strategies.

Main Methods:

• Systematic review following PRISMA guidelines, searching major databases and conference proceedings.
• Inclusion of prospective/retrospective studies (≥10 patients) with Stage I-III ASCC treated with curative-intent chemoradiotherapy.
• Narrative synthesis of data based on timepoint (baseline, mid-treatment, end-of-treatment, surveillance) and assay type (ctDNA, cfDNA, CTCs).

Main Results:

• Fifteen studies included, evaluating viral HPV ctDNA, tumor-informed ctDNA, cfDNA, and CTC assays.
• Higher CB detection rates and levels correlated with increased tumor burden and advanced stage.
• Mid-treatment ctDNA clearance predicted excellent outcomes; persistent ctDNA indicated treatment failure.
• End-of-treatment and surveillance ctDNA positivity predicted recurrence with high sensitivity and specificity, offering molecular lead time.

Conclusions:

• Circulating biomarker dynamics provide significant prognostic information in localized ASCC, especially during treatment and surveillance.
• Viral HPV and tumor-informed ctDNA assays show potential for guiding follow-up intensity and treatment strategies.
• Prospective, standardized trials are necessary to establish actionable thresholds and validate ctDNA-guided management.