Prognostic significance of L1CAM in cervical cancer: A narrative review

Cervical cancer remains a major contributor to cancer-related mortality among women worldwide, despite substantial progress in prevention and treatment strategies. While established prognostic factors such as tumor size, lymphovascular space invasion, and nodal status guide clinical decision-making, they lack sufficient specificity for individualized risk stratification. Consequently, there remains an unmet need for robust biomarkers capable of reliably predicting recurrence and treatment response. L1 cell adhesion molecule (L1CAM), a neural adhesion protein implicated in epithelial-mesenchymal transition (EMT), tumor invasion, and metastasis, has emerged as a candidate prognostic marker in several solid tumors, including gynecologic malignancies. Its role in cervical cancer, however, remains insufficiently defined. This narrative review synthesizes preclinical evidence and clinical studies evaluating L1CAM expression in cervical cancer, with an emphasis on its biological rationale, methodological challenges, and prognostic significance across different disease contexts. Data from early-stage and from locally advanced disease were critically appraised. Most early-stage studies have not demonstrated an independent prognostic effect of L1CAM, although associations with adverse histopathological features have been reported. In contrast, recent multicenter evidence suggests that high-level L1CAM expression (≥50%) may predict inferior pelvic control in patients undergoing chemoradiotherapy, underscoring a potential context-dependent prognostic role. Current evidence emphasizes the need for standardized immunohistochemistry protocols, prespecified positivity thresholds, and integration of L1CAM assessment with other. Prospective, adequately powered studies are essential to validate L1CAM as a clinically actionable biomarker and to determine whether its incorporation into prognostic models can enhance treatment personalization in cervical cancer.