宫颈腺鳞癌的治疗困境与精准治疗展望

Treatment Dilemmas and Prospects of Precision Therapy in Cervical Adenosquamous Carcinoma

摘要: 宫颈腺鳞癌(adenosquamous carcinoma, ASC)是一种兼具恶性腺上皮与恶性鳞状上皮成分的混合型宫颈癌，约占全部宫颈癌的3%~10%。现行指南尚无针对ASC的独立治疗标准，临床实践仍沿用基于SCC的诊疗规范，而ASC所特有的放疗抵抗性与系统性播散倾向，使同步放化疗疗效受限，以OUTBACK试验为代表的强化治疗策略亦未能改善生存，揭示了现行治疗范式与ASC生物学特性之间的深层错配。在精准治疗层面，帕博利珠单抗联合化疗已在PD-L1阳性晚期宫颈癌(含ASC)中证实明确生存获益；HER2靶向抗体偶联药物T-DXd在HER2高表达宫颈癌患者中客观缓解率达50.0%。建立基于PD-L1、HER2等分子标志物的个体化分层治疗体系，并开展专门针对ASC的前瞻性临床试验，是突破当前治疗困境的核心路径。

Abstract: Adenosquamous carcinoma (ASC) of the cervix is a rare mixed-type cervical cancer characterized by the coexistence of malignant glandular and squamous epithelial components, accounting for approximately 3%~10% of all cervical cancers. Current guidelines lack independent treatment standards for ASC, and clinical practice continues to follow protocols established primarily for squamous cell carcinoma (SCC). The radioresistance and systemic dissemination tendency intrinsic to ASC limit the efficacy of concurrent chemoradiotherapy (CCRT), and intensified treatment strategies—exemplified by the OUTBACK trial—have likewise failed to improve survival, revealing a fundamental mismatch between the current treatment paradigm and the biological nature of ASC. In terms of precision therapy, pembrolizumab combined with chemotherapy has demonstrated a clear survival benefit in PD-L1-positive advanced cervical cancer (including ASC); the HER2-targeting antibody-drug conjugate T-DXd achieved an objective response rate of 50.0% in patients with HER2-overexpressing cervical cancer. Establishing an individualized stratified treatment system based on molecular biomarkers such as PD-L1 and HER2, and conducting prospective clinical trials specifically designed for ASC, represent the core pathway to overcoming the current therapeutic impasse.