Human papillomavirus (HPV) is a non-enveloped, double-stranded DNA virus associated with a wide range of benign and malignant lesions affecting mucocutaneous surfaces. Although the oncogenic role of HPV in anogenital and oropharyngeal cancers is well-established, HPV-associated squamous cell carcinoma (SCC) arising in the extremities, particularly the toes, remains exceedingly rare. We report the case of a 78-year-old female farmer who presented with a persistent lesion between the fourth and fifth toes of her right foot, present for more than 1 month. Physical examination revealed a mildly purulent, horn-like lesion in the interdigital space. Magnetic resonance imaging (MRI) demonstrated a 37 × 17 mm enhancing soft-tissue mass suggestive of an inflammatory phlegmon with possible underlying osteomyelitis. Given the clinical and radiological findings, surgical amputation with wide debridement was performed. Histopathological examination revealed a well-differentiated SCC extending to, but not invading, the underlying bone. Surgical margins were negative. HPV DNA typing and cytologic evaluation confirmed the detection of HPV type 6, a low-risk subtype. This case highlights the importance of considering malignancy in chronic, wart-like lesions of the foot, especially in patients with occupational exposure. HPV-associated verrucous SCC, although rare, should be recognized to ensure accurate diagnosis and appropriate surgical management.

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