Keratoacanthoma: New Insight into Pathogenesis and Management of the Disease

Keratoacanthoma (KA) is a rapidly growing epithelial neoplasm characterized by clinical and histopathological features that often overlap with well-differentiated squamous cell carcinoma (SCC), posing diagnostic challenges. This review provides a comprehensive overview of KA, emphasizing advances in non-invasive diagnostic techniques such as dermoscopy, reflectance confocal microscopy (RCM), and line-field confocal optical coherence tomography (LC-OCT), which improve lesion characteriza-tion and differentiation from SCC. We discuss the histopathological phases of KA and highlight key features aiding in diagnosis. Furthermore, we explore the emerging role of human papillomavirus (HPV), particularly β-genus types, as a cofactor in KA car-cinogenesis through modulation of apoptosis and DNA damage response pathways, especially under ultraviolet (UV) radiation exposure. Therapeutic strategies remain centred on complete surgical excision; however, alternative treatments, including ra-diotherapy, cryotherapy, topical agents, and systemic retinoids, are discussed with their respective benefits and limitations. Finally, we review current HPV vaccines and novel vaccine candidates targeting a broad spectrum of mucosal and cutaneous HPV types, alongside promising off-label therapeutic applications. This review underscores the importance of integrated diagnostic and therapeutic approaches to optimize KA management and highlights future directions in understanding its pathogenesis and treatment.