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

// Matthias Dürst 1 , Heike Hoyer 2 , Christoph Altgassen 3 , Christiane Greinke 1 , Norman Häfner 1 , Alba Fishta 1 , Mieczyslaw Gajda 4 , Ute Mahnert 5 , Peter Hillemanns 6 , Thomas Dimpfl 7 , Miriam Lenhard 8 , K. Ulrich Petry 9 , Ingo B. Runnebaum 1 and Achim Schneider 10 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.