Dürst Matthias, Hoyer Heike, Altgassen Christoph, Greinke Christiane, Häfner Norman, Fishta Alba, Gajda Mieczyslaw, Mahnert Ute, Hillemanns Peter, Dimpfl Thomas, Lenhard Miriam, Petry K Ulrich, Runnebaum Ingo B, Schneider Achim
Department of Gynecology, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany.
Institute of Medical Statistics, Information Sciences and Documentation, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany.
Oncotarget. 2015 Sep 8;6(26):23015-25. doi: 10.18632/oncotarget.4132.
Up to 15% of patients with cervical cancer and pN0-status develop recurrent-disease. This may be due to occult metastatic spread of tumor cells. We evaluated the use of human-papillomavirus-(HPV)-mRNA as a molecular marker for disseminated tumor cells to predict the risk of recurrence. For this prospective, multi-center prognostic study, 189 patients free of lymphnode metastases by conventional histopathology could be analyzed. All patients underwent complete lymphadenectomy. Of each sentinel node (SLN) a biopsy was taken for the detection of HPV-E6-E7-mRNA. Median follow-up time after surgery was 8.1 years. HPV-mRNA could be detected in SLN of 52 patients (27.5%). Recurrence was observed in 22 patients. Recurrence-free-survival was significantly longer for patients with HPV-negative SLN (log rank p = 0.002). By Cox regression analysis the hazard ratio (95%CI) for disease-recurrence was 3.8 (1.5 - 9.3, p = 0.004) for HPV-mRNA-positive compared to HPV-mRNA-negative patients. After adjustment for tumor size as the most influential covariate the HR was still 2.8 (1.1 - 7.0, p = 0.030). In patients with cervical cancer and tumor-free lymph nodes by conventional histopathology HPV-mRNA-positive SLN were of prognostic value independent of tumor size. Particularly, patients with tumors larger than 20mm diameter could possibly benefit from further risk stratification using HPV-mRNA as a molecular marker.
高达15%的宫颈癌且pN0状态患者会出现疾病复发。这可能是由于肿瘤细胞的隐匿性转移扩散。我们评估了人乳头瘤病毒（HPV）-mRNA作为播散性肿瘤细胞的分子标志物以预测复发风险的应用。在这项前瞻性、多中心预后研究中，对189例经传统组织病理学检查无淋巴结转移的患者进行了分析。所有患者均接受了完整的淋巴结清扫术。对每个前哨淋巴结（SLN）进行活检以检测HPV-E6-E7-mRNA。术后中位随访时间为8.1年。在52例患者（27.5%）的SLN中检测到HPV-mRNA。观察到22例患者复发。HPV阴性SLN患者的无复发生存期显著更长（对数秩检验p = 0.002）。通过Cox回归分析，与HPV-mRNA阴性患者相比，HPV-mRNA阳性患者疾病复发的风险比（95%CI）为3.8（1.5 - 9.3，p = 0.004）。在将肿瘤大小作为最具影响力的协变量进行调整后，HR仍为2.8（1.1 - 7.0，p = 0.030）。在经传统组织病理学检查无淋巴结转移的宫颈癌患者中，HPV-mRNA阳性的SLN具有独立于肿瘤大小的预后价值。特别是，直径大于20mm的肿瘤患者可能会从使用HPV-mRNA作为分子标志物进行进一步风险分层中获益。
