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HPV 阴性宫颈癌:一种预后较差的宫颈癌特殊类型。

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

机构信息

Department of Pathology, Centre de Recerca en Salut Internacional de Barcelona (CRESIB), Hospital Clínic, University of Barcelona, Faculty of Medicine, Barcelona, Spain.

出版信息

BJOG. 2015 Jan;122(1):119-27. doi: 10.1111/1471-0528.13071. Epub 2014 Sep 17.

DOI:10.1111/1471-0528.13071
PMID:25229645
Abstract

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.

摘要

目的

使用高度敏感的聚合酶链反应(PCR)技术,我们重新分析了所有通过杂交捕获 2(HC2)检测为 HPV 阴性的宫颈癌(CC),以确定真正 HPV 阴性的患病率。我们还评估了经证实 HPV 阴性肿瘤患者的特征。

设计

观察性研究。

地点

西班牙巴塞罗那。

人群

一组 136 名患有 CC(32 例腺癌,104 例鳞状细胞癌)的女性,她们在治疗前进行了 HC2 检测。

方法

所有阴性病例均使用三种 PCR 检测(SPF10、GP5+/6+和 E7 特异性检测)进行重新分析和 HPV 基因分型。

主要观察指标

HPV 阴性和 HPV 阳性肿瘤的百分比。两组的临床病理特征和无病生存期(DFS)和总生存期(OS)。

结果

136 名女性中,有 14 名(10.2%)通过 HC2 检测为 HPV 阴性。通过基于 PCR 的技术重新分析后,仅 8/136(5.8%)肿瘤被确认为 HPV 阴性,而在 6 例中发现了不同的 HPV[HPV-11、-16(2 例)、-18、-45 和-68]。腺癌中 HPV 阴性的比例明显高于鳞状细胞癌(5/32,15.6%与 3/104,2.9%;P=0.017)。经证实 HPV 阴性的 CC 患者的 DFS 明显差于 HPV 阳性肿瘤患者[51.9 个月(95%CI 12.2-91.7 个月)与 109.9 个月(95%CI 98.2-121.5 个月);P=0.010]。在多变量分析中,HPV 阴性和国际妇产科联盟(FIGO)分期与进展和死亡风险增加相关。

结论

HC2 阴性结果在 CC 女性中并不常见,但在这些病例中,近一半病例通过更敏感的技术检测到 HPV。经证实 HPV 阴性的 CC 更常为腺癌,似乎与较差的 DFS 相关。

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