Single cell transcriptomics reveals dysregulated immnue homeostasis in different stages in HPV-induced cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer in humans. HPV persistence in the epidermis and excessive wart or squamous is associated with cancer development. Various viral warts can be found on the skin infected with HPV, like condyloma acuminatum and bowenoid papulosis (BP). At present, it is believed that BP is a potential malignant squamous cell carcinoma in situ. In this study, we reported a very rare case of HPV-positive patient with concurrence of BP and cSCC. This patient progressed at a very fast rate and transferred to death quickly. To reveal the cell microenvironment changes from normal skin (NS) to BP and cSCC after HPV infection, we performed scRNA-seq on four pathological lesions skin (NS, BP, paracancerous squamous cell carcinoma (pc-cSCC) and cSCC) from this patient. Among immune cells, CD52+ macrophages were only detected in pc-cSCC and cSCC tissue, and two clusters of T cells, CD8+ Tex cells and CD4+ Tregs as well as matrix cells like MMP1+, MMP11+ fibroblasts were increased in pc-cSCC and cSCC tissue. Widely interactions were also found among specific T cells/macrophages and keratinocytes, which might be involve in the cSCC progress. Targeting these cells or their interactions may be beneficial for the diagnosis and treatment of cSCC.