Cervical Cancer Therapies

Epidemiology & Impact

Cervical cancer remains a significant global health burden, with approximately 604,000 new cases and 342,000 deaths worldwide annually, making it the fourth most common cancer in women globally. In the United States, approximately 13,870 new cases and 4,360 deaths are expected in 2025, reflecting the impact of widespread Pap smear screening and HPV vaccination programs. However, striking disparities persist: incidence and mortality rates are 2-3 times higher in Black and Hispanic women compared to White women, and cervical cancer mortality in some US counties rivals rates in low-income countries. HPV infection, particularly types 16 and 18, causes virtually all cervical cancers, and HPV vaccination has already reduced HPV infections and precancerous lesions by over 80% in vaccinated populations. The WHO goal of eliminating cervical cancer as a public health problem (defined as incidence below 4 per 100,000) is achievable through vaccination, screening, and treatment of precancerous lesions.

Molecular Biology & Biomarkers

Cervical squamous cell carcinoma (approximately 70% of cases) and adenocarcinoma (approximately 25%) share HPV-driven molecular pathogenesis but have distinct genomic profiles. The HPV E6 and E7 oncoproteins degrade p53 and Rb respectively, abrogating key tumor suppressor checkpoints. Beyond HPV integration, cervical cancers commonly harbor amplifications in PIK3CA (approximately 35%), mutations in KRAS and PTEN (particularly in adenocarcinomas), and alterations in the JAK-STAT and Notch signaling pathways. PD-L1 expression is found in approximately 80% of cervical squamous cell carcinomas, providing the molecular basis for the exceptional activity of checkpoint immunotherapy in this disease. HER2 amplification or mutation is found in approximately 15% of cervical adenocarcinomas and may represent a therapeutic target. The combined positive score (CPS) for PD-L1 is used as a companion diagnostic for pembrolizumab eligibility.

Evolving Treatment Landscape

The treatment of advanced cervical cancer has undergone rapid transformation. For locally advanced disease, concurrent cisplatin-based chemoradiation remains the standard, with the KEYNOTE-A18 trial demonstrating that adding pembrolizumab to chemoradiation significantly improves progression-free and overall survival. For recurrent or metastatic disease, the KEYNOTE-826 trial established pembrolizumab plus chemotherapy (with or without bevacizumab) as the new first-line standard, doubling median overall survival for PD-L1-positive tumors compared to historical chemotherapy-only results. Tisotumab vedotin (Tivdak), an anti-tissue factor antibody-drug conjugate, received accelerated approval for previously treated recurrent or metastatic cervical cancer based on the innovaTV 204 trial. These advances have fundamentally altered the treatment algorithm, with immunotherapy now integrated across treatment settings. Active investigation continues with novel ADCs, bispecific antibodies, and therapeutic HPV vaccines.

EMA-Approved Therapies for Cervical Cancer

The European Medicines Agency (EMA) regulates drug approvals across the European Union. Below are key approvals with comparative timelines to FDA, demonstrating regulatory differences between regions.

For complete European approval details, visit ema.europa.eu ↗