Primary Sjögren's syndrome is associated with increased risk of malignancies besides lymphoma: A systematic review and meta-analysis

Autoimmun Rev. 2022 May;21(5):103084. doi: 10.1016/j.autrev.2022.103084. Epub 2022 Mar 24.


Objective: Patients with primary Sjögren's syndrome(pSS) have increased risk of non-Hodgkin lymphoma (NHL). However, whether pSS patients have increased risk of other malignancies is unclear. The aim of this study is to investigate the association between pSS and the risk of malignancy, with a focus on hematological malignancies besides lymphoma and solid tumors through a systematic review and meta-analysis.

Method: We searched PubMed and EMBASE by March 21st 2021. Inclusion criteria were as follows: (1) pSS was the exposure of interest; (2) newly developed malignancies were the outcome of interest; (3) standardized incidence ratio or relative risk with 95% confidence interval or essential data to calculate them were reported. (4) Study design was cohort study. Patient with other connective diseases were excluded. Quality assessment was conducted according to Newcastle-Ottawa Scale for cohort study. Random or fixed effect models were used to calculate the pooled SIR according to heterogeneity measured by I2.

Results: A total of 1003 articles were found by a comprehensive search in PubMed and EMBASE. Twenty-eight articles were eligible. Four of them were from the same database, and the one with longest observational span was chosen. Therefore, twenty-five articles were included for final analysis, which involved more than 47,607 pSS patients with the follow-up of more than 452,468 person-year. We found that pSS was significantly associated with increased risks of overall malignancy(pooled SIR 2.17, 95%1.57-3.00), hematological malignancy(pooled SIR 11.55, 95%CI 4.32-30.90) including NHL(pooled SIR 13.71, 95%CI 8.83-21.29), Hodgkin lymphoma(pooled SIR 8.84, 95%CI 5.00-15.61), multiple myeloma(pooled SIR 8.27, 95%CI 3.08-22.24), leukemia(pooled SIR 2.56, 95%CI 1.78-3.69) and solid tumors(pooled SIR 1.39, 95%CI 0.90-2.13) including lung cancer(pooled SIR 1.55, 95%CI 1.29-1.85), thyroid cancer(pooled SIR 2.05, 95%CI 1.20-3.48), non-melanoma skin cancer(pooled SIR 1.71, 95%CI 1.08-2.72), kidney/urinary tract cancer(pooled SIR 1.36, 95%CI 1.02; 1.81), liver cancer(pooled SIR 1.70, 95%CI 1.13-2.57) and prostate cancer(pooled SIR 1.50, 95%CI 1.02-2.22).

Conclusion: This meta-analysis showed that pSS patients had increased risk of overall cancer, which not only contributed by NHL, but also by other hematological malignancies and solid tumors.

Keywords: Malignancy; Primary Sjogren's syndrome; Solid tumor; non-Hodgkin lymphoma.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Cohort Studies
  • Hematologic Neoplasms* / complications
  • Hematologic Neoplasms* / epidemiology
  • Humans
  • Lung Neoplasms*
  • Lymphoma, Non-Hodgkin* / complications
  • Lymphoma, Non-Hodgkin* / etiology
  • Male
  • Risk Factors
  • Sjogren's Syndrome* / complications
  • Sjogren's Syndrome* / epidemiology