Whole-Genome HPV Liquid Biopsy for Pan-HPV-Associated Cancer Detection and Viral Physical State Classification: Cancer Cases
This study aims to develop and validate a comprehensive liquid biopsy approach for detecting human papillomavirus-associated cancers and characterizing the physical state of the HPV genome in plasma. HPV-DeepSeek uses whole-genome HPV sequencing of circulating cell-free DNA to detect HPV-associated malignancies across multiple anatomic sites, while HPV-SIGNAL is a computational classifier that uses HPV-DeepSeek sequencing data to distinguish episomal, rearranged, and integrated viral states. The study evaluates diagnostic performance in a cohort spanning nine HPV-associated cancer sites and investigates whether blood-based HPV physical state classification provides prognostic information. By linking viral integration patterns detected in plasma with clinical outcomes and validating these patterns through complementary tissue- and blood-based approaches, the study seeks to address an important limitation of existing circulating tumor HPV DNA assays, which can detect HPV-derived DNA but cannot determine viral physical state. The resulting sequencing dataset supports the development and validation of broadly applicable methods for pan-HPV-associated cancer detection, noninvasive classification of HPV genome structure, and assessment of viral integration as a potential biomarker of disease progression and survival.