Mitochondrial reprogramming in cervical cancer: crosstalk with tumor immunity, HPV oncogenic signaling, and therapeutic resistance.

Cervical cancer remains a major malignancy in women worldwide despite advances in human papillomavirus (HPV) vaccination, screening, and multimodal treatment. Persistent high-risk HPV infection is the principal driver of cervical carcinogenesis, yet viral oncogenesis alone cannot fully explain tumor progression, immune escape, and therapeutic failure. Increasing evidence suggests that mitochondrial reprogramming is a critical adaptive process that links HPV-driven transformation to metabolic plasticity, tumor immunity, and resistance to therapy. Beyond their canonical role in ATP production, mitochondria regulate redox homeostasis, mitochondrial dynamics, mitophagy, apoptotic priming, and mitochondria-derived danger signaling, thereby shaping both tumor-cell fitness and the surrounding immune microenvironment. In cervical cancer, HPV-associated oncogenic signaling promotes metabolic and mitochondrial remodeling, while downstream mitochondrial processes help sustain malignant growth, buffer oxidative and therapeutic stress, and influence immune responsiveness. Emerging studies further indicate that mitochondrial stress signals, particularly mitochondrial DNA-mediated innate immune activation, may connect tumor metabolism with anti-tumor immunity and immunotherapeutic sensitivity. At the same time, mitochondrial respiration, redox adaptation, and quality-control mechanisms contribute to chemoresistance and broader treatment tolerance. In this review, we summarize current evidence on how HPV oncogenic signaling reshapes mitochondrial biology in cervical cancer and discuss how mitochondrial reprogramming influences tumor immunity, immune evasion, and therapeutic resistance. We also highlight emerging mitochondria-targeted strategies and propose future directions for mechanistic and translational research. Together, these insights position mitochondrial reprogramming as both a conceptual framework and a potential therapeutic vulnerability in cervical cancer.