宫颈透明细胞癌研究进展综述

A Review of Research Progress on Clear Cell Carcinoma of the Cervix

摘要: 宫颈透明细胞癌(Clear Cell Carcinoma of the Cervix, CCAC)是一种罕见的宫颈腺癌亚型，其发病机制与HPV无关，具有独特的临床病理特征与侵袭性生物学行为。近年来，CCAC的发病率呈上升趋势，且约半数患者无己烯雌酚(DES)暴露史，提示存在其他潜在致癌因素。本文系统综述了CCAC在病因、临床表现、诊断、治疗及预后方面的最新研究进展。病因方面，除DES暴露外，苗勒管发育异常、输卵管–子宫内膜化生及驱动基因(如ARID1A、PIK3CA等)突变可能参与发病。临床表现以异常阴道出血为主，发病年龄呈双峰分布。诊断需结合影像学、组织病理学及免疫组化(如Napsin A、HNF-1β等标志物)进行综合判断。治疗上，早期患者以手术为主，局部晚期患者可采用手术联合放化疗，并对保留生育功能治疗进行了探讨。近年来，免疫治疗(如PD-1/PD-L1抑制剂)和靶向治疗(如针对PI3K-AKT-mTOR通路的抑制剂)为复发/转移性患者提供了新方向。预后与FIGO分期、淋巴结转移、淋巴血管间隙浸润等因素密切相关。未来需通过多中心合作与分子学研究，进一步优化个体化诊疗策略。

Abstract: Clear cell carcinoma of the cervix (CCAC) is a rare subtype of cervical adenocarcinoma, characterized by its HPV-independent pathogenesis, distinct clinicopathological features, and aggressive biological behavior. In recent years, the incidence of CCAC has been increasing, with approximately half of patients having no history of diethylstilbestrol (DES) exposure, suggesting the involvement of other potential carcinogenic factors. This article systematically reviews the latest research progress in the etiology, clinical manifestations, diagnosis, treatment, and prognosis of CCAC. In terms of etiology, besides DES exposure, Müllerian duct abnormalities, tubo-endometrial metaplasia, and driver gene mutations (such as ARID1A and PIK3CA) may contribute to tumorigenesis. Clinical manifestations primarily include abnormal vaginal bleeding, with a bimodal age distribution. Diagnosis requires a comprehensive evaluation integrating imaging, histopathology, and immunohistochemistry (e.g., markers such as Napsin A and HNF-1β). For treatment, early-stage patients are mainly treated with surgery, while locally advanced cases may undergo surgery combined with chemoradiotherapy. Fertility-sparing approaches have also been explored. Recently, immunotherapy (e.g., PD-1/PD-L1 inhibitors) and targeted therapy (e.g., inhibitors targeting the PI3K-AKT-mTOR pathway) have provided new options for recurrent/metastatic disease. Prognosis is closely associated with FIGO stage, lymph node metastasis, and lymphovascular space invasion. Future efforts should focus on multicenter collaborations and molecular studies to further optimize individualized diagnosis and treatment strategies.