The Clinical Utility of a Next-Generation Sequencing-Based Approach to Detecting Circulating HPV DNA in Patients with...

Area of Science:

• Oncology
• Virology
• Genetics

Background:

• Liquid biopsy offers potential beyond traditional human papillomavirus (HPV) circulating tumor DNA (ctDNA) assays.
• Evaluating a novel next-generation sequencing (NGS) HPV ctDNA assay is crucial for locally advanced and metastatic squamous cell cancer of the anal canal (mSCCA).

Purpose of the Study:

• To assess the clinical relevance of a novel NGS HPV ctDNA assay in patients with mSCCA.
• To determine if HPV ctDNA can serve as a biomarker for treatment response and prognosis.

Main Methods:

• Retrospective analysis of 77 plasma samples from 28 patients with HPV-related SCCA.
• Whole-genome sequencing of ctDNA using a 1.4 Mb hybrid-capture panel covering all 193 HPV types.
• Bioinformatic analysis to determine HPV type, copy number (CN), and integration sites.

Main Results:

• HPV ctDNA detected in 93% of cases, including uncommon subtypes.
• Higher HPV CN observed in metastatic versus locally recurrent/unresectable SCCA (p=0.043).
• HPV CN changes correlated with radiographic response (p=0.027).
• HPV integration detected in 82% of patients; higher integration associated with worse overall survival (p=0.003).

Conclusions:

• NGS of ctDNA can detect HPV and changes in HPV CN correlate with treatment response.
• HPV integration in ctDNA is an unfavorable prognostic biomarker in SCCA.
• This approach extends the utility of liquid biopsy for anal cancer management.