Evaluation of malignancy risk in patients with systemic sclerosis by autoantibody profile: a systematic review with meta-analysis

Objective Increased risk of cancer has been reported in systemic sclerosis (SSc) patients; however, the magnitude of this risk seems to vary with SSc-specific autoantibody profile. We aimed to review cancer risk in SSc patients by autoantibody subtypes. Methods We systematically reviewed literature related to cancer in SSc patients from January 1980 to December 2023 using PubMed, Embase, Scopus, and Cochrane library. We performed a meta-analysis comparing cancer risk in SSc patients with anticentromere antibody (ACA), anti-RNAP III antibody, and anti-Scl70 antibody. The search was conducted on 1 December 2023 and updated on 30 December 2023. Eligible studies were required to (1) include participants ≥ 18 years who fulfilled the 2013 ACR/EULAR, 1980 ACR modified, or LeRoy and Medsger classification criteria, (2) report cancer incidence with SSc-specific autoantibody, and (3) analyze relationship between SSc-specific autoantibodies and cancer. Results Twenty-two eligible studies were included and underwent meta-analysis. Anti-RNAP III positivity was associated with a significantly increased cancer risk in SSc patients (pooled relative risk (RR) 1.48; 95%CI 1.16–1.80), compared with anti-RNAP III-negative patients. While the presence of ACA was associated with a lower cancer risk (pooled RR 0.78; 95%CI 0.60–0.96) and may serve as an indicator for solely SSc, specifically limited systemic scleroderma. Conclusion Our meta-analysis showed that anti-RNAP III-positive SSc patients had a 48% higher risk of developing cancer compared with anti-RNAP III-negative SSc patients. Therefore, physicians should be aware of this elevated risk. Rigorous screening of malignancy by age-appropriate and relevant family history is recommended.