A Review on Contemporary Paradigms and Mechanistic Advances in the Therapeutic Management of Cervical Cancer

Review Article

Abstract

Cervical cancer is the primary cause of gynecologic oncologic mortality internationally, disproportionately affecting developing economies lacking systematic screening and vaccination infrastructures. Carcinogenesis is driven by persistent integration of high-risk human papillomaviruses, wherein oncoproteins E6 and E7 break cell-cycle checkpoints via ubiquitination of p53 and functional inactivation of the retinoblastoma protein. While historical interventions relied primarily on radical extirpative surgery for early-stage disease and cisplatin-based concurrent chemoradiotherapy for locally advanced stages, the therapeutic landscape has evolved substantially. The 2018 revision of the International Federation of Gynecology and Obstetrics staging system fundamentally altered clinical prognostication by codifying radiological and pathological lymph node status alongside three-dimensional metric stratifications. Image-guided adaptive brachytherapy has elevated local control rates while attenuating gastrointestinal and genitourinary toxicities. Systemic intervention for persistent, recurrent, or metastatic disease has transitioned from cytotoxic doublets to targeted regimens incorporating anti-angiogenic monoclonal antibodies, immune checkpoint blockades targeting programmed cell death protein 1, and antibody-drug conjugates directed against cell-surface antigens such as tissue factor. Recent biological treatments include cell cycle checkpoint inhibition via Wee1 kinase inhibition, synthetic lethality exploiting poly (ADP-ribose) polymerase inhibition in DNA repair pathways, and autologous tumor-infiltrating lymphocyte transfer platforms. The aim of this review is to discuss about the contemporary management standards, translating landmark Phase III clinical trials into oncologic practice including prevention, definitive local targeting, and systemic drug therapies.