HPV8 Field Cancerization in a Transgenic Mouse Model Is Due to Lrig1+ Keratinocyte Stem Cell Expansion

The study investigated the role of hair follicle (HF) keratinocyte stem cells in β-HPV-induced skin carcinogenesis using a transgenic mouse model expressing the HPV8 early region. The HPV8 transgenic mice exhibited thicker skin and a hyperproliferative epidermis compared to wild-type mice. Notably, there was a significant proliferation of Lrig1+ keratinocyte stem cells, with a 2.8-fold expansion and a 3.8-fold increase in colony-forming efficiency, while other stem cell populations did not show similar proliferation. This proliferation was linked to nuclear p63 expression and a switch to ΔNp63 isoforms. The findings suggested that β-HPV field cancerization originated from the HF junctional zone, potentially leading to squamous cell carcinoma.