Role of Stromal CD25+/CD8+ Lymphocyte Ratio in Patients With Grade 2-3 Cervical Intraepithelial Neoplasia (CIN 2-3): A Retrospective Single-center Study

Abstract

Background/aim: This study aimed to assess the role of the stromal CD25+/CD8+ (Cluster of Differentiation) lymphocyte ratio and other immunohistochemical markers in predicting the risk of recurrence and human papillomavirus (HPV) persistence after Loop Electrosurgical Excision Procedure (LEEP) conization in patients with grade 2-3 cervical intraepithelial neoplasia (CIN2-3).

Patients and methods: A retrospective analysis was conducted on 72 patients who underwent LEEP for CIN2-3 in our Department. Criteria for enrollment included HPV genotyping before and after surgery and a follow-up time ≥18 months. Immunohistochemical analysis assessed CD8+ cytotoxic T cells and CD25+ regulatory T cells in the cervical stroma, and the CD25+/CD8+ ratio was computed. Recurrence of CIN2-3 and HPV persistence after LEEP were the endpoints of the study.

Results: CIN2-3 recurrence occurred in 13.9% of patients with smoking, HPV-16/18 infection, positive surgical margins, and CIN3 histology being significant risk factors. A CD25+/CD8+ ratio >1.25 was associated with a shorter disease-free survival (DFS) (p=0.033) and HPV persistence at 18 months (p=0.017) after LEEP at univariate analysis. Adjuvant HPV vaccination reduced the recurrence risk (p=0.004). A lympho-monocyte infiltrate consisting of at least 10% CD25+ T cells was significantly associated with HPV persistence at 18 months (p=0.0046).

Conclusion: The CD25+/CD8+ ratio is a promising biomarker for identifying patients at higher risk of CIN2-3 recurrence and HPV persistence post-LEEP. These findings highlight the role of immune profiling in the management of patients affected by CIN2-3 and support the integration of vaccination and personalized follow-up strategies.

Keywords: CD25+/CD8+ lymphocyte ratio; Cervical intraepithelial neoplasia (CIN2-3); HPV genotyping; HPV persistence; cytotoxic T cells (CD8+); loop electrosurgical excision procedure (LEEP); recurrence risk; regulatory T cells (CD25+); stromal lymphocyte infiltrate.