Clinical and autoantibody associations with malignancy in systemic sclerosis: A systematic review and meta-analysis.

Authors

Jaivikash Raghupathy, Wei Shan Teoh, Abhiram Kanneganti, Hanis Bte Abdul Kadir, Gim Gee Teng, Pearl Shuang Ye Tong, Lauren V Host, Kathleen Morrisroe, Mandana Nikpour, Andrea Hsiu Ling Low, Scleroderma Clinical Trials Consortium (SCTC) Cancer Working Group

Published in

Rheumatology (Oxford, England). Jul 02, 2026. Epub Jul 02, 2026.

Abstract

This meta-analysis examines factors associated with malignancy in systemic sclerosis (SSc).
A systematic search of Embase, MEDLINE and Cochrane Library databases was conducted from inception to 7 December 2024. Case-control and cohort studies reporting associations with malignancy in SSc were included. Random-effects meta-analyses were performed to pool study results. Mean differences (MD) for age and odds ratios (OR) for binary outcomes using frequency counts were calculated. Study quality was assessed using Newcastle-Ottawa Scale.
Thirty-five studies comprising 27 624 SSc patients were analysed. Patients with malignancy developed SSc at an older age (MD + 4.01, 95% CI 1.24- 6.78). Significant associations for malignancy included male gender (OR 1.36), smoking (OR 1.27), pulmonary hypertension (PH, OR 1.32), interstitial lung disease (ILD; OR 1.41), diffuse cutaneous SSc (OR 1.14), positive anti-RNAPIII (OR 1.79) and anti-centromere antibody (ACA, OR 0.83) and negative anti-nuclear antibody (OR 1.39). In sensitivity analyses of high quality studies, male gender, smoking, PH and anti-RNAPIII remained significant. Subgroup analyses by malignancy types and development in relation to SSc diagnosis revealed positive associations of lung malignancy with male gender (OR 2.72), smoking (OR 2.38), anti-Scl-70 (OR 2.45) and ILD (OR 2.98), while ACA was inversely associated (OR 0.32). Anti-RNAPIII was associated with breast malignancy (OR 2.17) and early/concurrent malignancy (OR 2.85), and digital ulceration (OR 0.39) with later malignancy development.
Malignancy association in SSc is influenced by clinical phenotype and autoantibody profile. Our findings suggest a risk-stratified approach to malignancy surveillance rather than uniform screening.

PMID:
42391056
Bibliographic data and abstract were imported from PubMed on 03 Jul 2026.

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