高危型人乳头瘤病毒阴性宫颈癌患者临床病理特征分析

Clinical and Pathological Features of High-risk HPV-negative Cervical Cancer

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(χ^2=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。

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-riskHPV-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(χ^2=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.