宫颈神经内分泌癌的发病机制与治疗进展

Pathogenesis and Treatment Advances in Neuroendocrine Carcinoma of the Cervix

摘要: 宫颈神经内分泌癌(Neuroendocrine Carcinoma of the Cervix, NECC)是一种罕见的侵袭性强的妇科恶性肿瘤，占全部宫颈癌的0.9%~1.5%，与常见的宫颈鳞状细胞癌和腺癌相比，NECC患者多在发病早期出现淋巴结转移和远处转移，预后极差，各期5年生存率均明显低于同期鳞癌患者。近年来，高通量测序和scRNA-seq的普及使得NECC的发病机制、肿瘤微环境等的研究不断深入。其中，高危型人乳头瘤病毒(HPV)感染(HPV18和HPV16)在NECC的发生发展中起主要作用。HPV整合入宿主基因组联合MYC、SOX、NR4A等基因的热点模式是恶性转化的关键。目前，治疗NECC的指南较少，主要以根治手术，铂类联合依托泊苷为主的全身化疗、同步放化疗为辅。靶向药物(抗血管生成药物)以及免疫检查点抑制剂(PD-1/PD-L1单抗)的研究为改善晚期及复发性NECC患者生存带来了希望，本文将综述宫颈神经内分泌癌的发病机制和最新治疗进展，并为个体化精准治疗提供依据。

Abstract: Neuroendocrine Carcinoma of the Cervix (NECC) is a rare and highly aggressive gynecological malignancy that accounts for 0.9%~1.5% of all cervical cancers; compared with common cervical squamous cell carcinoma and adenocarcinoma, NECC is more likely to develop lymph node metastasis and distant metastasis at an early stage, leading to an extremely poor prognosis, and its 5-year survival rate at all stages is significantly lower than that of patients with concurrent squamous cell carcinoma. In recent years, the popularization of high-throughput sequencing and single-cell RNA sequencing (scRNA-seq) has further deepened the research on the pathogenesis and tumor microenvironment of NECC, among which high-risk human papillomavirus (HPV) infection (HPV16 and HPV18) plays a major role in the occurrence and progression of NECC, and the integration of HPV into the host genome combined with hotspot alterations of genes such as MYC, SOX and NR4A is the key to malignant transformation. At present, there are few specific guidelines for the treatment of NECC, and the clinical regimens are mainly based on radical surgery and systemic chemotherapy with platinum combined with etoposide, supplemented by concurrent chemoradiotherapy. Researches on targeted drugs (anti-angiogenic agents) and immune checkpoint inhibitors (PD-1/PD-L1 monoclonal antibodies) have brought new hope for improving the survival of patients with advanced and recurrent NECC. This article reviews the pathogenesis and latest therapeutic progress of neuroendocrine carcinoma of the cervix, so as to provide a basis for individualized precise treatment.