Mengjia Huang, Shuang Li
Small cell carcinoma of the cervix (SCCC) is a rare yet highly aggressive subtype of cervical cancer (CC), characterized by early invasion, high metastatic potential, frequent recurrence, and extremely poor prognosis, which severely impairs women's physical and mental health. Currently, high-risk human papillomavirus (hr-HPV, particularly HPV18) infection is recognized as one of the core drivers underlying the initiation and progression of SCCC. Malignant evolution is not triggered by a single infection event but is cooperatively regulated at multiple molecular levels, including HPV genome integration, critical gene mutations, and aberrant activation of multiple signaling pathways. In addition, SCCC exhibits an HPV-independent oncogenic pathway mainly mediated by somatic mutations in tumor protein 53 (TP53) and retinoblastoma 1 (RB1), thus forming a dual pathogenic mechanism. Based on current clinical understanding and molecular mechanisms, this paper reviews the molecular pathogenesis and subtypes of SCCC, reveals the associations between tumor heterogeneity, therapeutic resistance, and metastasis, and proposes potential novel targets for the treatment of SCCC. This study innovatively presents a closed-loop model of two-way empowerment between basic research and clinical application. It emphasizes that basic research should be oriented toward real clinical problems and highlights the reciprocal feedback of clinical practice on basic research, thereby achieving dynamic iteration and collaborative breakthroughs in both fields.