The Evolving Landscape of HPV-related Cervical Malignancies: a Comprehensive Review

Cervical cancer is the fourth most frequently diagnosed and fourth most deadly cancer in women globally, despite it being largely preventable due to its strong association with human papillomavirus (HPV) infection. While widespread implementation of HPV vaccination and cervical screening has led to marked reductions in incidence and mortality in high-income countries, survival outcomes remain a challenge in low-to middle-income countries. Current treatment strategies for cervical cancer are largely stage-dependent. Early-stage disease is typically managed surgically, whereas locally advanced cervical cancer is treated with concurrent chemoradiotherapy. However, patients with recurrent, persistent, or metastatic disease face significantly worse outcomes, with limited therapeutic options and considerable treatment-related toxicity. Immunotherapy has emerged as a promising treatment modality in advanced-stage cervical cancer, particularly through immune checkpoint inhibitors. These agents aim to enhance the body’s anti-tumor immune response and have demonstrated meaningful activity in advanced disease. This review outlines the evolving landscape of cervical cancer treatment regimens, with a special focus on immunotherapies and combination therapies that can offer a positive efficacy-toxicity balance and therefore hold promise for women at more advanced stages of the disease. Furthermore, it highlights recent advances in promising novel therapeutic directions that may shape the management of both early-stage and more advanced stages of HPV-related cervical cancer.