Novel nanopore sequencing method for determining Human Papillomavirus integrations in tumors without the need for whole genome sequencing

Abstract

Human papillomaviral (HPV) integrations into host human genome, a key event in cervical carcinogenesis, are currently mapped through laborious and expensive sequencing methodologies. We developed and validated a novel library preparation strategy for nanopore sequencing to generate long targeted reads with HPV and human chimeric sequences. Using this strategy, we validated known HPV integrations in HeLa (HPV18) and SiHa (HPV16) cell lines. We also mapped integration sites in five HPV+ cervical cancer patients, which were confirmed by whole genome and Sanger sequencing. Our nanopore-based method provides a precise and efficient strategy to capture HPV integrations crucial for understanding tumorigenesis.