Abstract: Background　Cervical cancer is a common malignant tumor of the female reproductive system，which mainly caused by persistent infection of high-risk human papillomavirus （HPV）．However，clinical studies found that a considerable number of cervical cancer patients are high-risk HPV-negative，and such patients have increased risks of postoperative recurrence，cancer cell invasion and metastasis.Objective　To describe the clinical and pathological features of high-risk HPV-negative cervical cancer patients.Methods　This analysis was performed on 1 416 cervical cancer inpatients with complete clinicopathological data recruited from Women's Hospital，School of Medicine Zhejiang University during 2003 to 2016.Among them，1 296 were high-risk HPV-positive，and 120 were high-risk HPV-negative showed by preoperative Hybrid Capture II HPV Test （HCII）．Paraffin-embedded cervical cancer samples of high-risk HPV-negative patients were reexamined by real-time PCR，and those were truly negative for high-risk HPV were assigned to high-risk HPV-negative group，and were compared with the same number of high-risk HPV-positive patients randomly selected from the 1 296 cases.Data about age of onset，age at first birth，number of births，clinical stage，and pathological type of the two groups were collected.Results　The rate of high-risk HPV-negative detected by HCII was 8.5%（120/1 416）．And of these 120 cases，89 were found to be truly negative for high-risk HPV by real-time PCR，achieving a rate of truly high-risk HPV-negative of 6.3%.The coincidence rate of the two tests was 74.2% （89/120）．The mean onset age for high-risk HPV-negative，and high-risk HPV-positive patients was （45.2±4.2） years （range 28-75），（46.3±5.1） years（range 21-78），respectively.No significant differences were observed in terms of mean age of onset，distribution of onset age，distributions of age at first birth，number of births，and clinical stage between the two groups （P>0.05），but there was significant difference in pathological type distribution between them （χ2=22.062，P=0.001）．Conclusion　Real-time high-risk HPV test is highly sensitive in detecting high-risk HPV DNA.Compared with high-risk HPV-positive cervical cancer，although the overall incidence rate of HPV-negative cervical cancer is not high，the incidence rates of adenocarcinoma，adenosquamous carcinoma and other rare histologic subtypes are higher.

Key words: Uterine cervical neoplasms；Human papillomavirus；Pathological conditions, sign and symptom；Polymerase chain reaction

摘要： 背景　宫颈癌是女性常见的生殖道恶性肿瘤。高危型人乳头瘤病毒（HPV）的持续感染是其主要病因。然而临床研究发现，有相当一部分宫颈癌患者高危型HPV检测结果为阴性，且这类患者术后复发风险、肿瘤细胞侵袭以及转移风险均增加。目的　分析高危型HPV阴性宫颈癌患者的临床病理特征。方法　2003—2016年浙江大学医学院附属妇产科医院住院治疗、临床病理资料完整且术前有HPV-HC2检测结果的宫颈癌患者共1 416例，经第2代杂交捕获技术（HC-Ⅱ）检测高危型HPV阳性宫颈癌患者1 296例，高危型HPV阴性宫颈癌患者120例。调取120例高危型HPV阴性宫颈癌组织石蜡标本，采用实时荧光聚合酶链式反应（PCR）法对高危型HPV进行再检测，获取高危型HPV真阴性患者为高危型HPV阴性组。从1 296例高危型HPV阳性宫颈癌患者中以随机数字表法选取与高危型HPV真阴性组等量的患者为高危型HPV阳性组。收集两组患者的发病年龄、初次生育年龄、分娩次数、临床分期及病理类型等。结果　1 416例宫颈癌患者中，HC-Ⅱ法检测高危型HPV阴性120例，阴性率为8.5%。实时荧光PCR法显示，高危型HPV仍为阴性89例，阴性率为6.3%，两次检测符合率为74.2%（89/120）。高危型HPV阴性组患者发病年龄28~75岁，平均发病年龄（45.2±4.2）岁；高危型HPV阳性组患者发病年龄21~78岁，平均发病年龄（46.3±5.1）岁。两组患者平均发病年龄、各发病年龄构成、初次生育年龄、分娩次数、临床分期比较，差异均无统计学意义（P>0.05）。两组患者病理类型比较，差异有统计学意义（χ2=22.062，P=0.001）。结论　采用实时荧光PCR法检测宫颈癌组织石蜡样本中的高危型HPV是一种高敏感度的检测方法。与高危型HPV阳性宫颈癌相比，高危型HPV阴性宫颈癌发病率不高，但其腺癌、腺鳞癌及其他少见类型癌的比例高于高危型HPV阳性的宫颈癌患者。

关键词: 宫颈肿瘤；人乳头瘤病毒；病理状态, 体征和症状；聚合酶链反应