Abstract
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 characterization 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 carcinogenesis through modulation of apoptosis and DNA damage response pathways, especially under ultraviolet (UV) radiation exposure. Therapeutic strategies remain centered on complete surgical excision; however, alternative treatments, including radiotherapy, 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. 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.