人乳头瘤病毒阴性的子宫颈肿瘤。
HPV-negative tumors of the uterine cervix.
机构信息
Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Clínic - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Institut de Salut Global de Barcelona (ISGlobal), Barcelona, Spain.
出版信息
Mod Pathol. 2019 Jul;32(8):1189-1196. doi: 10.1038/s41379-019-0249-1. Epub 2019 Mar 25.
Human papillomaviruses (HPV) are the causative agents of virtually all cervical carcinomas. Nevertheless, a small proportion of cervical cancer are negative for HPV, although the significance of this finding remains unclear. We aimed to provide insight into the differential clinico-pathological characteristics of this unusual subset of HPV-negative cervical cancer. We performed HPV-DNA detection using a highly sensitive PCR test (SPF10) and p16 immunostaining in 214 cervical carcinomas specimens from women treated at the Gynecological Oncology Unit of the Hospital Clinic (Barcelona, Spain) from 2012 to 2015. The clinical and pathological characteristics, including disease-free survival and overall survival, of HPV-negative and -positive cervical carcinomas were compared. Twenty-one out of 214 tumors (10%) were negative for HPV DNA. HPV-negative tumors were more frequently of the non-squamous type (9/21, 43% vs. 37/193, 19%; p < 0.01) and showed negative p16 staining (9/21; 43% vs. 7/193; 4%; p < 0.01). HPV-negative tumors were more frequently diagnosed at advanced FIGO stage (19/21, 91% vs. 110/193, 57%; p < 0.01) and more frequently had lymph node metastases (14/21, 67% vs. 69/193, 36%; p < 0.01). Patients with HPV-negative cervical cancer had a significantly worse disease-free survival (59.8 months, 95% confidence interval 32.0-87.6 vs. 132.2 months, 95% confidence interval 118.6-145.8; p < 0.01) and overall survival (77.0 months, 95% confidence interval 47.2-106.8 vs. 153.8 months, 95% confidence interval 142.0-165.6; p = 0.01) than women with HPV-positive tumors. However, only advanced FIGO stage and lymph node metastases remained associated with a poor disease-free survival and overall survival on multivariate analysis. In conclusion, our results suggest that a low percentage of cervical cancer arise via an HPV-independent pathway. These HPV-negative tumors are diagnosed at advanced stages, show higher prevalence of lymph nodes metastases and have an impaired prognosis.
人乳头瘤病毒（HPV）是几乎所有宫颈癌的致病因素。然而，一小部分宫颈癌 HPV 检测为阴性，尽管这一发现的意义尚不清楚。我们旨在深入了解 HPV 阴性宫颈癌这一不寻常亚组的不同临床病理特征。我们使用高度敏感的 PCR 检测（SPF10）和 p16 免疫组化检测了 214 例来自西班牙巴塞罗那 Clinic 妇科肿瘤学病房的宫颈癌患者的 214 例宫颈癌标本，这些患者于 2012 年至 2015 年接受治疗。比较了 HPV 阴性和阳性宫颈癌的临床和病理特征，包括无病生存和总生存。214 例肿瘤中有 21 例（10%）HPV DNA 检测为阴性。HPV 阴性肿瘤更常为非鳞状类型（9/21，43% vs. 37/193，19%；p<0.01），并显示 p16 染色阴性（9/21；43% vs. 7/193；4%；p<0.01）。HPV 阴性肿瘤更常被诊断为晚期 FIGO 分期（19/21，91% vs. 110/193，57%；p<0.01），更常发生淋巴结转移（14/21，67% vs. 69/193，36%；p<0.01）。HPV 阴性宫颈癌患者的无病生存率（59.8 个月，95%置信区间 32.0-87.6 vs. 132.2 个月，95%置信区间 118.6-145.8；p<0.01）和总生存率（77.0 个月，95%置信区间 47.2-106.8 vs. 153.8 个月，95%置信区间 142.0-165.6；p=0.01）明显低于 HPV 阳性肿瘤患者。然而，多变量分析仅显示晚期 FIGO 分期和淋巴结转移与无病生存和总生存不良相关。总之，我们的结果表明，一小部分宫颈癌是通过 HPV 无关途径发生的。这些 HPV 阴性肿瘤在晚期被诊断，更常发生淋巴结转移，预后不良。
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