Evaluation of CXCR3 Gene Expression in Iraqi Women with Cervical Intraepithelial Neoplasia Induced By Human Papillomavirus

Abstract

Background:    Cytokines and chemokines play a crucial role in initiating the early immune response against High-Risk Human papillomavirus (HR-HPV) infection, hence preventing the progression of cervical lesions to cervical cancer (CC). The C-X-C motif chemokine ligand 10 (CXCL10) interacts with C-X-C motif chemokine receptor 3 (CXCR3) to facilitate immune responses by stimulating and attracting specific types of immune cells.
Objective:    To explore the role of the CXCR3 in women infected or uninfected with HR-HPV-induced tumors. 
Methods:    The study included 100 female patients diagnosed with cervical intraepithelial neoplasia (CIN); twenty-two samples were shown to be HR-HPV positive, while thirteen samples were not. The presence of HR-HPV was confirmed using a real-time polymerase chain reaction (PCR) kit from Sacase, Italy and 20 apparently healthy women as a control group. Two-step reverse transcription PCR (RT-qPCR) was used to assess the expression of CXCR3 in both CC cells and cervical neoplasia in different stages {atypical squamous cells of undetermined significance (ASC-US), CIN I&II, and high-grade squamous intraepithelial lesion (HSIL)} samples. 
Results:    Results showed that gene expression of CXCR3 level was substantially and significantly upregulated (p <0.001) in the cervix tissue of women with CIN in (early and moderated) stages of disease-infected HR-HPV but not in the control group. On the other hand, at late stages of disease (HSIL) and CC stage, the level of CXCR3 was significantly downregulated (p >0.05). Receiver operating characteristic analysis showed that CXCR3 had 73% sensitivity with 100% specificity.
Conclusion:    The results suggested that these molecules may serve as potential biomarkers for CIN progression of women infected with HPV and as an indicator of immune responses in surviving patients. Also, reductions in CXCR3 gene expression may reflect viral immune escape/or viral clearances.
Keywords:    HR-HPV, CXCR3, real time PCR, cervical neoplasia, cervical cancer, Iraqi women
Citation:    Allos MM, Naif HM. Evaluation of CXCR3 Gene expression in Iraqi women with cervical intraepithelial neoplasia induced by Human Papillomavirus. Iraqi JMS. 2025; 23(2): 377-383. doi: 10.22578/IJMS.23.2.20