We present a case of human papillomavirus-associated squamous cell carcinoma arising between the ventral toes. A 60-year-old man presented with a 6-year history of a growth between the right fourth and fifth toes that had previously been thought to be secondary to hammertoe deformity. Initial biopsy favored verruca vulgaris with associated fungal hyphae and he was treated accordingly. Subsequent biopsy showed squamous cell carcinoma in situ with positive for high-risk human papillomavirus subtypes 16 and 18. He was successfully treated with Mohs surgery. This is the first published case of human papillomavirus 18-associated interdigital squamous cell carcinoma of the toes treated with Mohs surgery.

Cells of the immune system that reside in barrier epithelia provide a first line of defense against pathogens. Langerhans cells (LCs) and CD8(+) tissue-resident memory T cells (TRM cells) require active transforming growth factor-β1 (TGF-β) for epidermal residence. Here we found that integrins αvβ6 and αvβ8 were expressed in non-overlapping patterns by keratinocytes (KCs) and maintained the epidermal residence of LCs and TRM cells by activating latent TGF-β. Similarly, the residence of dendritic cells and TRM cells in the small intestine epithelium also required αvβ6. Treatment of the skin with ultraviolet irradiation decreased integrin expression on KCs and reduced the availability of active TGF-β, which resulted in LC migration. Our data demonstrated that regulated activation of TGF-β by stromal cells was able to directly control epithelial residence of cells of the immune system through a novel mechanism of intercellular communication.