A state-of-the-art systematic review of cancer in hidradenitis suppurativa

Abstract

Purpose: Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with an increased risk of malignancy. The aim of this systematic review was to investigate the prevalence of different malignancies in HS.

Methods: This review meets the PRISMA criteria. A data-driven approach was used to conduct the research, which involved a detailed keyword search. The study considered meta-analyses, experimental studies, case-control studies, cross-sectional studies, cohort studies, and recently published cases, published in English or German. Excluded were reviews, summaries, and letters to the editor, as well as studies, which are not based on the human population.

Results: Out of the initial 443 publications found, 25 met the inclusion criteria for this systematic review. Patients with HS have a significantly increased risk of cancer, up to 50%. Additionally, the risk of oropharyngeal, central nervous system, colorectal, prostate, vulvar and non-melanocytic skin cancers increase with the severity of HS. The likelihood of comorbid lymphoma in patients with HS is significantly higher compared to healthy controls. In severe cases of HS, malignant degeneration of lesions in the groin, perianal, perineal, and gluteal region can occur in up to 4.6% of cases. This leads to the development of cSCC, which often have a complicated course, are more refractory to treatment and associated with a poorer outcome. The pathogenic mechanisms responsible for the malignant transformation of HS are currently unknown.

Conclusions: Patients with HS have a higher risk of cancer compared to the general population. Untreated, long-standing HS lesions can lead to complicated malignant degeneration resulting in cutaneous squamous cell carcinoma. The mechanisms underlying this malignant degeneration are not fully understood. HS patients also have an increased risk of developing other cancers, including prostate, oral, pharyngeal and colorectal cancers of the central nervous system and lymphomas.

Keywords: HS; Hidradenitis suppurativa; colorectal carcinoma; cutaneous squamous cell carcinoma; lymphoma; malignancy; malignant diseases; oropharyngeal carcinoma.

Figure 1.

Flowchart with the research strategy of this systematic review.

Figure 2.

Shows the different ratios and the overall cancer risk in comparison; or, odds ratio; RR: relative risk; aHR, adjusted hazard ratio; *Compared to healthy controls; **Compared to healthy male controls; ***compared to healthy female controls.

Figure 3.

Shows an overview of possible pathomechanisms of malignant transformation of chronic Hidradenitis suppurativa (HS) into cutaneous squamous cell carcinoma or marjolin ulcer. Genetic alterations in Hidradenitis suppurativa (HS) and comorbid smoking lead to impairment of the NOTCH signaling pathway, which activates the expression of proto-oncogenes (POs) and suppresses that of the tumour suppressor gene 53 (TP53). Locoregional infections with high-risk human papillomaviruses (HPV) support the genetic effects of malignant development. Increased expression of undifferentiated cytocreatins can be observed in creatinocytes. Treatment with biologics can impair the anti-tumour response of T cells and other body cells. Chronic wounds can promote degeneration through recruitment and activation of fibroblasts, deposition of extracellular matrix components, infiltration of immune cells and hyperinflammation, neovascularisation and cell lineage plasticity. RB, Retinoblastom-Protein; HGF, hepatocyte growth factor; CTGF, connective growth factor.