title: Prognostic value of HPV-mRNA in sentinel lymph nodes of cervical cancer patients with pN0-status.
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.
authors.affiliation: Department of Gynecology, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Dürst
authors.affiliation: Institute of Medical Statistics, Information Sciences and Documentation, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Hoyer
authors.affiliation: Department of Gynecology and Obstetrics, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Altgassen
authors.affiliation: Department of Gynecology, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Greinke
authors.affiliation: Department of Gynecology, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany.
authors.forename: Norman
authors.initials: N
authors.lastname: Häfner
authors.affiliation: Department of Gynecology, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany.
authors.forename: Alba
authors.initials: A
authors.lastname: Fishta
authors.affiliation: Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany.
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Gajda
authors.affiliation: Department of Gynecology and Obstetrics, Helios Klinikum Erfurt GmbH, Erfurt, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Mahnert
authors.affiliation: Department of Gynecology and Obstetrics, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hillemanns
authors.affiliation: Department of Gynecology and Obstetrics, Klinikum Kassel GmbH, Kassel, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dimpfl
authors.affiliation: Department of Gynecology and Obstetrics, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Lenhard
authors.affiliation: Department of Gynecology and Obstetrics, Klinikum Wolfsburg, Wolfsburg, Germany.
authors.forename: K Ulrich
authors.initials: KU
authors.lastname: Petry
authors.affiliation: Department of Gynecology, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany.
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Runnebaum
authors.affiliation: Institute for Cytology and Dysplasia, Fürstenbergkarree, Berlin, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Schneider
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology*; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics* / Q000302:isolation & purification; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral
keywords: HPV-mRNA; cervical cancer; disease free survival; prognosis; sentinel lymph node