Association of HPV viral load, estrogen receptor α signaling, and inflammatory serum biomarkers with cervical cancer progression

The persistence of HPV is a high-risk factor of cervical cancer development, although the development of the disease is highly dependent on estrogen receptor signaling and HPV-associated serum biomarkers that have a synergistic effect in promoting the development of malignancy. The aim of the study is examine the relationship between HPV viral load, e s trogen receptor expression, and the presence of serum biomarkers and their interactive effects in the development of cerv i cal cancer. The case control study was carried out in one of the tertiary teaching hospitals in Iraq in the period between January 2024 and January 2025 involving 100 women diagnosed with cervical cancer via histopathology and 50 age-matched healthy women as controls. ELISA and immunohistochemistry methods were used to measure serum estradiol , CA-125, IL-6, TNF-α and CRP, and high-risk HPV viral load was measured using the qPCR , after obtaining ethical a p p roval . The findings showed that there is similarity in the age distribution of the cervical cancer patients and the control with body mass index and parity being significantly higher in the former. There were significant differences in the HPV viral load and ER of high-grade cases as compared to low-grade. Patients especially with high viral load had high levels of serum estradiol , CA-125, IL-6, TNF -α, and CRP. C orrelation analysis showed that there were strong positive links between the HPV load, hormonal activity, the presence of inflammatory biomarkers, and the aggressiveness of the tumor s , demonstra t ing the combined effect of all the factors in cervical cancer development. The interplay between increased HPV viral load and estrogen receptor signaling and general systemic inflammation leads to the cervical cancer progression. High hormonal and inflammatory biomarkers probably encourag e tumor growth and aggressiveness through the effects of su p porting viral persistence, dysregulation of the immune system, and oncogenic pathways that depend on estrogen.