Sex Differences in Systemic Immune-Inflammation Index (SII) in Solid Cancers: A Systematic Review and Meta-Analysis

Background: The systemic immune-inflammation index (SII), calculated from peripheral neutrophil, platelet, and lymphocyte counts, is an emerging biomarker of systemic inflammation and immune status in patients with cancer. Although biological sex influences immune and inflammatory responses, whether SII levels differ between female and male patients with solid malignancies remains unclear. This systematic review and meta-analysis aimed to investigate the association between sex and elevated SII levels in patients with solid cancers. Methods: A systematic literature search was conducted in PubMed, Scopus, Web of Science, and the Cochrane Library. Studies reporting sex-stratified frequencies of high and low SII levels were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a random-effects model with restricted maximum likelihood estimation and the Hartung–Knapp adjustment. Heterogeneity, prediction intervals, and leave-one-out sensitivity analyses were examined. Risk of bias was assessed using ROBINS-E. The review was registered in PROSPERO (CRD420261456390). Results: Six studies involving 2503 patients with solid cancers (829 females and 1674 males) were included, of whom 984 presented elevated SII levels. Female patients showed lower odds of elevated SII compared with male patients (OR = 0.71, 95% CI: 0.50–1.00; p = 0.048). Moderate between-study heterogeneity was observed (I2 = 52.3%). However, the 95% prediction interval (0.32–1.55) included the null value, and leave-one-out analyses demonstrated that statistical significance was lost following the exclusion of five of the six studies. Furthermore, all included studies were judged to have high overall risk of bias. Conclusion: Overall, our findings support the concept that sex should be considered an important biological variable in studies evaluating inflammation-based biomarkers in oncology and highlight the need for sex-stratified analyses in future clinical research.