HPV-negative carcinoma of the uterine cervix: a distinct type of cervical cancer with poor prognosis

HPV-negative carcinoma of the uterine cervix: a distinct type of cervical cancer with poor prognosis
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DOI:
10.1111/1471-0528.13071
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发表时间:
2015-01-01
影响因子:
5.8
通讯作者:
del Pino, M.
del Pino, M.
中科院分区:
医学1区
文献类型:
--
作者:
Rodriguez-Carunchio, L.;Soveral, I.;del Pino, M.

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目的应用高灵敏度的聚合酶链反应(PCR)技术,对所有经杂交捕获2(HC 2)检测为人乳头瘤病毒(HPV)阴性的宫颈癌(CC)进行再分析,以确定HPV真阴性的发生率。我们还评估了经证实HPV阴性的肿瘤患者的特征。设计观察性研究。地点:西班牙巴塞罗那。人群:136名女性CC患者的队列研究。方法对治疗前HC 2检测阴性的32例腺癌和104例鳞癌患者进行HPV基因分型(SPF 10、GP 5 +/6+和E7特异性测定)。主要结果测量确认的HPV阴性和HPV阳性肿瘤的百分比。两组患者的临床病理特征、无病生存期(DFS)和总生存期(OS)。在通过基于PCR的技术进行再分析后,仅8/136(5.8%)的肿瘤被确认为HPV阴性,而在6个病例中鉴定出不同的HPV [HPV-11、-16(2个肿瘤)、-18、-45和-68]。证实HPV阴性在腺癌中比在鳞状细胞癌中更常见(分别为5/32,15.6%和3/104,2.9%; P = 0.017)。确诊HPV阴性的CC患者的DFS显著差于HPV阳性肿瘤女性患者[51.9个月(95% CI 12.2-91.7个月)vs 109.9个月(95% CI 98.2-121.5个月); P = 0.010]。在多变量分析HPV阴性和国际妇产科联合会(FIGO)分期与疾病进展和mortality.Conclusions的风险增加HC 2阴性结果是一个不常见的发现,在女性CC,但在这些情况下,HPV几乎有一半被确定为更敏感的技术。经证实HPV阴性的CC更常见于腺癌,并且似乎与较差的DFS相关。
Objective Using highly sensitive polymerase chain reaction (PCR) techniques, we reanalysed all cervical carcinomas (CCs) found to be human papillomavirus (HPV)-negative by Hybrid Capture 2 (HC2) to determine the prevalence of true HPV-negativity. We also evaluated the characteristics of the patients with tumours with confirmed HPV-negativity.Design Observational study.Setting Barcelona, Spain.Population A cohort of 136 women with CC (32 adenocarcinomas, 104 squamous cell carcinomas) who had pre-treatment HC2 testing.Methods All negative cases were reanalysed and genotyped for HPV using three PCR assays (SPF10, GP5+/6+ and E7-specific assay).Main outcome measures Percentage of confirmed HPV-negative and HPV-positive tumours. Clinicopathological features and disease-free survival (DFS) and overall survival (OS) of both groups.Results Fourteen of 136 women (10.2%) were negative for HPV by HC2. After reanalysis by PCR-based techniques only 8/136 (5.8%) tumours were confirmed as HPV-negative, whereas in six cases different HPVs were identified [HPV-11, -16 (two tumours), -18, -45, and -68]. Confirmed HPV-negativity was more frequent in adenocarcinomas than in squamous cell carcinomas (5/32, 15.6% versus 3/104, 2.9%, respectively; P = 0.017). Patients with CCs with confirmed HPV-negativity had significantly worse DFS than women with HPV-positive tumours [51.9 months (95% CI 12.2-91.7 months) versus 109.9 months (95% CI 98.2-121.5 months); P = 0.010]. In the multivariate analysis HPV-negativity and International Federation of Gynecology and Obstetrics (FIGO) staging were associated with increased risk of progression and mortality.Conclusions An HC2-negative result is an uncommon finding in women with CC, but in almost half of these cases HPVs are identified by more sensitive techniques. CCs with confirmed HPV-negativity are more frequently adenocarcinomas, and seem to be associated with worse DFS.