Systemic immune-inflammation and inflammation response indices as potential adjunctive biomarkers for invasive cervical disease and cytology underestimation in patients undergoing cervical conization: a multicenter study

Cervical cancer is the fourth most common malignancy among women worldwide. The Systemic Immune-Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI) are easily calculated from routine complete blood count and have been associated with various malignancies. However, their potential role in the management of cervical cancer, especially in patients undergoing conization, remains unclear. The aim of this multicenter study was to evaluate the association between these indices and cervical lesion severity based on cytological findings and histopathological results following conization. In this retrospective multicenter cohort study, data from 1039 patients who underwent loop conization between 2021 and 2024 were analyzed. SII and SIRI values were significantly higher in patients with invasive carcinoma than in those with lower-grade lesions ( p < 0.001 for all comparisons). Both indices were significantly higher in patients with cytology underestimation (SII: p = 0.025; SIRI: p = 0.011). ROC analyses showed limited discriminatory performance for cytology underestimation, with AUCs of 0.555 for SII and 0.562 for SIRI, and negative predictive values of 87.4% and 86.8%, respectively. In multivariable analyses, SIRI was significantly associated with invasive histopathology in both complete-case (adjusted OR 1.926, p = 0.012) and multiple-imputation models (adjusted OR 1.562, p = 0.002), whereas SII reached statistical significance only after multiple imputation. In the analysis of cytology underestimation, SIRI showed significant associations in univariable and HR-HPV-adjusted models, although associations were less consistent across fully adjusted models. SII and SIRI are simple, cost-effective and minimally invasive biomarkers. They were associated with histopathological severity and thus may have potential as exploratory adjunctive biomarkers for identifying patients at increased risk for invasive carcinoma before conization. However, their limited discriminatory performance for cytology underestimation precludes conclusions regarding their clinical diagnostic utility. Their potential role as adjunctive components of future multimodal risk stratification models requires further validation.