Molecular pathways of inflammation in cervical cancer development

Abstract

Cervical cancer develops through a multifactorial process driven by persistent high-risk human papillomavirus (HPV) infection, host immune dysregulation, and progressive molecular alterations. While HPV infection is a necessary initiating factor, viral persistence alone is insufficient for malignant transformation. Chronic inflammation within the cervical microenvironment critically promotes genomic instability, immune evasion, and tumor progression. Key inflammatory signaling pathways—including NF-κB, JAK/STAT, and COX-2–mediated prostaglandin cascades—facilitate a pro-tumorigenic state by enhancing cell proliferation, inhibiting apoptosis, and supporting angiogenesis. Concurrently, oxidative stress, inflammation-induced DNA damage, epigenetic reprogramming, and microRNA dysregulation further accelerate carcinogenesis. A bidirectional interaction exists between HPV oncoproteins and inflammatory pathways, whereby viral factors exploit host immune responses to sustain oncogenic signaling. The tumor microenvironment, shaped by immune-cell polarization, hypoxia, and microbiome-related inflammation, also contributes to disease progression. Targeting inflammatory mechanisms therefore represents a promising strategy for improving prevention, prognostic evaluation, and therapeutic outcomes in HPV-associated cervical cancer.