Oncotarget

Clinical Research Papers:

Prognostic value of HPV-mRNA in sentinel lymph nodes of cervical cancer patients with pN0-status

Matthias Dürst _, Heike Hoyer, Christoph Altgassen, Christiane Greinke, Norman Häfner, Alba Fishta, Mieczyslaw Gajda, Ute Mahnert, Peter Hillemanns, Thomas Dimpfl, Miriam Lenhard, K. Ulrich Petry, Ingo B. Runnebaum and Achim Schneider

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Oncotarget. 2015; 6:23015-23025. https://doi.org/10.18632/oncotarget.4132

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Abstract

Matthias Dürst1, Heike Hoyer2, Christoph Altgassen3, Christiane Greinke1, Norman Häfner1, Alba Fishta1, Mieczyslaw Gajda4, Ute Mahnert5, Peter Hillemanns6, Thomas Dimpfl7, Miriam Lenhard8, K. Ulrich Petry9, Ingo B. Runnebaum1 and Achim Schneider10

1 Department of Gynecology, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany

2 Institute of Medical Statistics, Information Sciences and Documentation, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany

3 Department of Gynecology and Obstetrics, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany

4 Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany

5 Department of Gynecology and Obstetrics, Helios Klinikum Erfurt GmbH, Erfurt, Germany

6 Department of Gynecology and Obstetrics, Medizinische Hochschule Hannover, Hannover, Germany

7 Department of Gynecology and Obstetrics, Klinikum Kassel GmbH, Kassel, Germany

8 Department of Gynecology and Obstetrics, Ludwig-Maximilians-University Munich, Campus Grosshadern, Munich, Germany

9 Department of Gynecology and Obstetrics, Klinikum Wolfsburg, Wolfsburg, Germany

10 Institute for Cytology and Dysplasia, Fürstenbergkarree, Berlin, Germany

Correspondence to:

Matthias Dürst, email:

Keywords: sentinel lymph node, cervical cancer, HPV-mRNA, prognosis, disease free survival

Received: April 15, 2015 Accepted: April 20, 2015 Published: May 14, 2015

Abstract

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.


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