Cervical cancer is one of the most common malignant tumors of the female reproductive system. In most low-income countries, there is a paucity of progress in the reduction of cervical cancer incidence and mortality. Recent treatment innovations – such as immune checkpoint inhibitors, antibody–drug conjugates (ADCs), and therapeutic HPV vaccines – are marking a paradigm shift in cervical cancer therapy. However, the pace of innovation, distribution of trial activities, and diversity of treatment mechanisms vary significantly across regions and stages of development. Here, we present a comprehensive analysis of the cervical cancer clinical trial landscape, providing a temporal, mechanistic, and geographic overview of ongoing studies. This assessment aims to identify progress, gaps, and future opportunities on the path to eliminating cervical cancer. This study adheres to the 2025 TITAN Guidelines for the use of AI in research and reporting1. This study analyzed cervical cancer trials using the INFORMA database (https://pharma.id.informa.com/). Using the MeSH term “Cervical Cancer,” we identified 1857 interventional trials (phases I–IV), excluding observational, preclinical, and abstract studies, as well as duplicates. Data extraction was completed in April 2025. Multi-regional trials were counted across all reported countries, yielding non-mutually exclusive geographic counts. Duplicates were removed, and incomplete fields were flagged. Trial status was categorized as ongoing, completed, terminated, or withdrawn. Two independent reviewers verified the dataset. The indicators analyzed included temporal trends, phases, MOA, sponsors, and geography. From 2010 to 2024, the total number of cervical cancer clinical trials increased steadily, corresponding to a compound annual growth rate (CAGR) of 0.8% (Fig. 1A). This surge aligns with the global rise in immunotherapy checkpoint inhibitor trials in oncology. Phase I trials rose from fewer than 15 per year in 2010 to nearly 50 by 2024, with significant upward trends confirmed for both Phase I (Z = −4.63, P < 0.001) and Phase II (Z = 3.05, P = 0.002) by a Cochran–Armitage trend test, reflecting intensified early exploration of emerging modalities (e.g., bispecific antibodies, CAR-T, mRNA vaccines). This pattern likely reflects the accelerated maturation of immuno-oncology pipelines and more efficient early-phase designs. An analysis of trial status revealed that completed trials accounted for the largest proportion, with 498 trials currently ongoing (Fig. 1B). As shown in Figure 1C, immuno-oncology leads the MOA landscape, with immune checkpoint inhibitors representing its largest sub-category. Progression-free survival and objective response rate dominated the primary endpoints (62%), followed by overall survival (OS; 25%), quality of life (QoL; 9%), and biomarker response (4%) (Fig. 1D). Academic institutions sponsored 874 trials, followed by other pharmaceutical companies (Fig. 1E). In terms of geographical distribution, trial activity was concentrated in China (750, 40.4%) and the United States (640, 34.5%). Spain ranked third (184, 9.9%), followed by the United Kingdom (156, 8.4%), France (155, 8.3%) (Fig. 1F). Despite the heavy disease burden, sub-Saharan Africa and Latin America remain underrepresented. Vaccine and screening trials are more likely to be conducted in low- and middle-income countries, while late-stage treatment trials remain concentrated in high-income countries. Figure 1.: The panorama of clinical trials for cervical cancer. (A) Trends in the number of clinical trials and trial phases over time. (B) Trial status distribution of clinical trials. (C) Mechanisms of actions. (D) Primary endpoint distribution of clinical trials. (E) Sponsor type distribution of clinical trials (Top 5). (F) Country distribution of clinical trials (Top 10). Our analysis describes a dynamic and diverse cervical cancer research ecosystem. It is worth emphasizing that, as shown in the mechanism analysis diagram, in addition to immune-oncology approaches, ADCs (e.g., trastuzumab vedotin targeting tissue factor) also account for a significant proportion. MOA counts are non-exclusive; for like-for-like comparisons, we also assign a mutually exclusive primary MOA aligned to the Informa taxonomy, adjudicated by a pre-specified hierarchy. The diversification of mechanisms of action (MOA) reflects a shift from cytotoxic-driven approaches to precision immunotherapy. Therapeutic vaccines – once hindered by low efficacy – are now benefiting from next-generation platforms and novel adjuvant strategies that enhance antigen presentation and T cell activation2,3. Over the past 5 years, we have witnessed an acceleration of innovation driven by immunotherapy and targeted biologics. In the KEYNOTE-826 trial, the greatest benefit was observed in patients with PD-L1 CPS ≥ 1, establishing pembrolizumab plus chemotherapy (with or without bevacizumab) as a new standard of care for advanced cervical cancer. Therapeutic vaccines are being combined with bevacizumab, pembrolizumab, and carboplatin with manageable safety and promising activity4. Therapeutic vaccines such as VGX-3100 and ISA101b were initially designed for HPV-related lesions or head and neck tumors. However, several late-phase studies are now evaluating their potential role in advanced cervical cancer5,6. Furthermore, preclinical development momentum is equally significant: CRISPR-engineered HPV-specific CAR-T cells have been demonstrated to exhibit enhanced tumor infiltration and persistence. The administration of oncolytic viruses, which are capable of carrying immune modulators, has been demonstrated to produce synergistic effects in conjunction with checkpoint blockade therapy. The first human trials of mRNA vaccines delivered by nanoparticles targeting E6/E7 are underway. This study has several limitations that should be acknowledged. First, this study relied solely on the INFORMA database without cross-validation against other registries such as ClinicalTrials.gov, which may introduce selection bias or underrepresentation of certain trial types (e.g., academically sponsored studies or studies led by LMICs low- and middle-income countries). Second, potential delays in database updates could affect the accuracy of trial status and outcome reporting. Despite these limitations, the study provides a valuable, timely, and comprehensive overview of global cervical cancer clinical trial trends for researchers, policymakers, and clinicians. The evolution of integrative treatment paradigms is reshaping the surgical management of cervical cancer. With immune checkpoint inhibitors, ADCs, and next-generation therapeutic vaccines demonstrating improved response rates, neoadjuvant systemic therapy is increasingly positioned as a key component in locally advanced disease. Early evidence suggests that meaningful tumor regression may enable selected patients to shift from extensive radical procedures toward organ- or nerve-preserving approaches, and in highly selected young patients, fertility-sparing surgery. Concurrently, biomarkers such as PD-L1 expression, tumor mutation burden, tissue factor expression, and HPV-specific immune signatures are refining preoperative assessment. Biomarker-guided response prediction can help distinguish patients who derive maximal benefit from surgery from those who may avoid major procedures through effective neoadjuvant therapy, thereby reducing treatment-related morbidity. According to GLOBOCAN 2022, cervical cancer accounted for approximately 604 000 new cases and 342 000 deaths worldwide, with the highest burden observed in LMICs, particularly in sub-Saharan Africa and South Asia. To ensure that advances in systemic therapy meaningfully improve global outcomes, future efforts should expand pilot programs in high-burden LMICs, integrate molecular biomarkers into trial designs, and combine preventive strategies (vaccination and screening) with therapeutic innovation to form a cohesive elimination framework. Strengthening LMIC participation in late-phase trials through regional research networks, public–private partnerships, and capacity-building initiatives will be essential to promote equitable innovation. For surgically oriented trials, prospective integration of systemic and operative strategies – incorporating endpoints such as pathological complete response, tumor regression grade, organ- and function-preservation rates, quality of life, and long-term pelvic floor outcomes – will be critical to defining a multidisciplinary treatment model that maximizes survival while minimizing surgical and systemic toxicity. In order to achieve the WHO’s 2030 cervical cancer elimination goals, it is essential that coordinated advances in research funding, infrastructure, and policy be made collectively. Additional trial numbers can be found in the supplemental Digital Content file, available at: https://links.lww.com/JS9/G972.
Wang et al. (Wed,) studied this question.