Abstract
BACKGROUND: Research on the impact of tumor-infiltrating immune cells(TIICs) combined with systemic inflammatory response (SIR) factors on cervical lesions and the prognosis of squamous cell cervical cancer (SCC) is limited. Therefore, this study aimed to evaluate the predictive and prognostic significance of TIICs and SIR factors in cervical epithelial lesions, specifically non-cervical epithelial lesions (NC), high-grade squamous intraepithelial lesions (HSIL), and SCC. METHODS: This retrospective study analyzed 163 patients in three cohorts: NC (n = 59), HSIL (n = 52), and SCC (n = 52). Tumor-infiltrating immune cells (TIICs) in the tumor/lesion center and adjacent stroma were assessed via immunohistochemistry and multiplex immunofluorescence, while systemic inflammatory response (SIR) factors were derived from preoperative blood counts. The primary outcome was relapse-free survival (RFS) in the SCC cohort, analyzed using Cox proportional hazards regression. RESULTS: TIICs were significantly elevated in the HSIL group compared with those in the NC group, accompanied by reduced platelet counts (PLT). The tumor stroma (TS) exhibited a greater degree of TIICs than the tumor/lesion center (TC) in both the HSIL and SCC groups. The presence of CD163+, CD11b+, and FOXP3 + TIICs, along with PLT levels, emerged as key indicators associated with the advanced histological stage. Compared to tTIICs, sTIICs demonstrated superior diagnostic performance in differentiating between HSIL and SCC groups. Lower levels of PLT (hazard ratio [HR] = 5.047, 95% confidence interval [CI]:1.373–18.540, P = 0.015), higher CD4 + T cells (HR = 0.211, 95%CI:0.062–0.722, P = 0.008), and FOXP3 + regulatory T cells (Tregs) (HR = 0.245, 95%CI:0.073–0.820, P = 0.010) were identified as poor prognostic indicators for recurrence-free survival (RFS) in SCC. A combination of FOXP3 + Tregs and PLT provided a more robust prediction of SCC recurrence. An increase in exhausted CD4 + T cells likely explains the observation that higher CD4 + T-cell infiltration correlated with lower RFS in SCC. CONCLUSION: The spatial distribution of TIICs, particularly the density in the tumor stroma, increases across the histological spectrum of cervical lesion severity. A signature combining FOXP3 + Treg cells and preoperative platelet counts provides a robust model for predicting SCC recurrence. Furthermore, the accumulation of exhausted CD4 + T cells appears to be a hallmark of disease advancement and poor prognosis, offering potential targets for personalized immunotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12905-026-04274-9.