Clinical and cellular factors influencing radiotherapy response and toxicity in uterine cervical cancer

Cervical cancer remains a major global health burden, with locally advanced disease requiring multimodal treatment, including radiotherapy combined with cisplatin-based chemotherapy or hyperthermia. This thesis investigated clinical and cellular determinants of treatment response and outcomes in cervical cancer. First, the interaction between radiotherapy and hyperthermia was examined, focusing on treatment dose, temperature, and sequencing. Higher radiotherapy doses and hyperthermia temperatures reduced cervical cancer cell survival, while a shorter interval between the two modalities enhanced tumour control in preclinical models and patients, accompanied by increased DNA damage and radiosensitisation. Second, the prognostic and biological significance of high-risk human papillomavirus (HPV) infection was investigated. A systematic review and clinical study demonstrated that higher HPV viral load was associated with more aggressive disease, increased lymph node and distant metastasis, and poorer recurrence-free and overall survival. High HPV viral load was also associated with increased p16INK4a expression and reduced CD3+ tumour-infiltrating lymphocytes, suggesting an immunosuppressive tumour microenvironment. Finally, treatment-related toxicity was evaluated in patients receiving radiotherapy for gynaecological cancers. Although overall survival did not differ significantly, patients with greater radiation-induced toxicity had longer recurrence-free survival, suggesting that increased toxicity may reflect enhanced intrinsic radiosensitivity. Collectively, these findings provide insights into the biological and clinical determinants of treatment response and support the development of personalised treatment strategies for patients with cervical cancers.