Abstract
BACKGROUND: This systematic review explores the increased cancer risk in patients with hidradenitis suppurativa (HS), particularly cutaneous squamous cell carcinoma (SCC) and lymphoma. Chronic inflammation and immune dysregulation in HS are identified as key factors contributing to malignant transformation, often observed in areas of prolonged tissue damage. OBJECTIVES AND RESULTS: The NOTCH signaling pathway, disrupted by smoking, plays a dual role in cancer, acting as both a tumor suppressor and a proto-oncogene depending on the context. Mutations in NOTCH and TP53 are common in SCC linked to HS, with a prevalence of 0.5% to 4.6%, predominantly in men and localized to the buttock and anogenital regions. Histological analyses suggest that malignant transformation occurs within keratinized epithelium, supported by altered cytokeratin expression. Immune dysregulation in HS-affected areas, compounded by scarring and lymphatic disruption, further exacerbates tumorigenic potential. While anti-TNF-alpha therapies have been implicated in cancer risk, conflicting evidence and meta-analyses suggest no consistent increase in non-melanoma skin cancers (NMSC). Similarly, IL-17 inhibitors show potential risks but lack robust evidence in HS-specific populations. CONCLUSION: In conclusion, HS-associated malignancies, particularly SCC, underscore the need for further research to elucidate the mechanisms linking chronic inflammation to cancer development. Insights from such studies could guide preventative and therapeutic strategies, improving outcomes for HS patients.