Association of High-Risk Human Papillomavirus (HPV) Genotypes with Immune Biomarker (B7-H4, TGF-β2, and IFN-γ) Expression in Women with Normal versus Abnormal Cervical Cytology

Abstract

Background: Human papillomavirus (HPV) infection is recognised as the major aetiological agent that causes cervical carcinogenesis worldwide. In Middle Eastern populations, the interaction between HPV infection and host immune response is still poorly understood, especially in terms of cytokine production and immune checkpoint molecules. Objective: The study aimed to measure the prevalence and genotypic distribution of high-risk HPV (HR-HPV) and how the immune markers B7-H4, TGF-β2, and IFN-γ are different between HPV-positive and HPV-negative women with normal and abnormal cervical cytology in Baghdad, Iraq. Materials and Methods: We have conducted a case-control study from August 2020 to February 2025 at Al-Yarmouk Teaching Hospital, Baghdad, Iraq. We have enrolled 300 women with cervical abnormalities (cases) and 300 healthy women (controls). HPV was identified and detected with the Xpert HPV assay, and cervical cytology was assessed with liquid-based cytology. The enzyme-linked immunosorbent assay (ELISA) measurement of B7-H4, TGF-β2 and IFN-γ was performed. Results: High-risk HPV infection also occurred in 7.3% of cases (No. = 22 of 300), and no infection was found in controls. HPV-16 was the most common genotype among HR-HPV-positive cases (45.5%), followed by HPV-18/45 (31.8%) and other high-risk genotypes (22.7%). Normal cytology was found in 91.3% of cases, while low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and atypical squamous cells of undetermined significance (ASCUS) were 5.7%, 2.0%, and 1.0% respectively. Relative to HPV-negative controls, HPV-positive cases exhibited a significant elevation of B7-H4 (4.1 ± 1.3 ng/mL versus 2.6 ± 0.6 ng/mL; p < 0.001) and a significant reduction of IFN-γ (0.5 ± 0.2 pg/mL versus 0.9 ± 0.3 pg/mL; p < 0.001). Conclusion: The findings show a relatively low prevalence of HPV infection in women at Al-Yarmouk Teaching Hospital in Baghdad, HPV-16 being the most prevalent genotype. The characteristic immunological marker profiles associated with HPV infection may be useful for HPV-associated cervical pathology assessment.