Abstract
Background: Human papillomavirus (HPV) infection is increasingly recognized as associated with endometrial immunological disturbance and adverse reproductive outcomes. Yet the systemic immunological and hormonal correlates of this association, and their diagnostic utility in clinical settings, remain poorly defined. Aim: This study aimed to assess the association of HPV infection with systemic immunological and oxidative stress markers and to evaluate their contribution to adverse pregnancy outcomes in women of reproductive age. Methods: A cross-sectional comparative study enrolled 120 women across four groups (n=30 each): Group 1 (HPV-negative controls), Group 2 (HPV-positive without complications), Group 3 (adverse pregnancy outcomes, HPV-negative), and Group 4 (HPV-positive with adverse pregnancy outcomes). Serum interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), peripheral blood natural killer (PB-NK) cells, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), progesterone, and estradiol were measured. Binary logistic regression and receiver operating characteristic (ROC) curve analyses were applied to identify independent predictors and diagnostic thresholds. Results: Group 4 showed the highest IL-6 (12.6±2.1 pg/mL), TNF-α (15.8±2.6 pg/mL), IFN-γ (17.2±3.1 pg/mL), and MDA (6.2±1.2 nmol/mL), with the lowest IL-10, PB-NK cells, SOD, GSH, progesterone, and endometrial thickness (p<0.001 to p=0.003). Logistic regression identified MDA (OR=3.06), TNF-α (OR=2.12), and IL-6 (OR=1.84) as significant independent predictors of adverse outcomes. ROC analysis revealed MDA as the strongest single diagnostic marker (AUC=0.891, cutoff ≥4.2 nmol/mL); the combined biomarker model achieved AUC=0.934. Conclusion: HPV infection is independently associated with systemic pro-inflammatory and oxidative stress dysregulation, hormonal insufficiency, and impaired endometrial receptivity. The MDA-TNF-α-IL-6 panel shows promising clinical utility for identifying women at elevated risk of pregnancy failure, warranting incorporation into preconception assessment protocols.
Keywords
Human papillomavirus; endometrial receptivity; pregnancy outcomes; oxidative stress; cytokines; logistic regression; ROC analysis