Hidradenitis suppurativa-associated squamous cell carcinoma: a systematic review of clinical, molecular, and risk factor insights

Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the pilosebaceous unit that can rarely harbor squamous cell carcinoma (SCC). Despite its clinical relevance, comprehensive characterization of HS-SCC - including risk factors, histological and molecular features, and outcomes - remains limited.

A systematic review of the literature was performed to identify all published cases of HS-associated SCC. Data on demographics, HS features, tumor characteristics, human papillomavirus (HPV) status, treatments, and outcomes were extracted to identify risk phenotypes and prognostic factors.

A total of 174 cases were included. Most patients were male (78.4%), with a mean age of 53 years, and nearly all presented Hurley stage III HS affecting the lower trunk, predominantly the gluteal region. Tumors were generally large, often arising from sinus tract epithelium, and were commonly well-differentiated. HPV infection was detected in 28.6% of cases, predominantly HPV-16. Metastasis occurred in 54.3% of patients. Overall mortality was 52.8%, with mean survival until death of 11.9 months. Male sex, gluteal location, poor histologic differentiation, and presence of metastasis were associated with worse outcomes. Risk phenotypes include males >50 years, long-standing HS (>10 years), Hurley III disease with complex sinus tracts involving the lower trunk; in females, vulvar involvement is an additional risk factor.

HS-SCC is rare but highly aggressive. Early recognition of high-risk phenotypes, regular monitoring of chronic HS lesions, timely surgery, and imaging assessment are essential to improve outcomes. HPV vaccination may offer preventive benefits in susceptible patients.