title: Combined p16 and p53 expression in cervical cancer of unknown primary and other prognostic parameters : A single-center analysis.
abstract: OBJECTIVE
  Cervical cancer of unknown primary (CUP) represents an uncommon and heterogeneous subentity of head and neck cancer. However, both optimal diagnostics and therapy remain unclear. An improved understanding of the underlying pathology is essential to enable future tailored therapies and optimized outcomes.
  
  
  METHODS
  We retrospectively analyzed 53 patients with head and neck CUP and 48 available cervical lymph node specimens. All patients have received radiotherapy between 2007 and 2015. Preradiotherapy involved lymph node specimens were analyzed for p16 and p53 immunoreactivity. The prognostic relevance of the combined p16 and p53 status and other clinical parameters were examined by univariate and multivariate analyses.
  
  
  RESULTS
  Median patient age was 61.5 years and median irradiation dose to the involved nodal levels was 66 Gy. Of the 48 evaluated specimens, 13 (27%) were p16-positive and 31 (64.6%) p53-positive. After a median follow up of 32.9 months, patients with p16-negative and simultaneously p53-positive tumors showed a significantly inferior tumor-specific survival (TSS) compared to those with either p16+/p53-, p16+/p53+, or p16-/p53- (univariate: p = 0.055, multivariate: p = 0.038). Other factors with an adverse impact on TSS in the univariate analysis were smoking history (p = 0.032) and nodal stage (p = 0.038).
  
  
  CONCLUSIONS
  The combined p16- and p53-expression status in cervical metastases of CUP may represent a simple method for risk stratification. Further validation of these biomarkers in large prospective trials is essential to design rational trials for CUP treatment optimization.
authors.affiliation: Department of Radiation Oncology, University Hospital, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590, Frankfurt, Germany.
authors.forename: Müjdat
authors.initials: M
authors.lastname: Yildirim
authors.affiliation: Department of Radiation Oncology, University Hospital, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590, Frankfurt, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Müller von der Grün
authors.affiliation: Senckenberg Institute of Pathology, University Hospital, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Ria
authors.initials: R
authors.lastname: Winkelmann
authors.affiliation: Department of Radiation Oncology, University Hospital, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590, Frankfurt, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.|German Cancer Consortium (DKTK), partner site: Frankfurt a. M., Germany.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Fokas
authors.affiliation: Department of Radiation Oncology, University Hospital, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590, Frankfurt, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Rödel
authors.affiliation: Department of Biomedical Statistics, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Hanns
authors.initials: H
authors.lastname: Ackermann
authors.affiliation: Department of Radiation Oncology, University Hospital, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590, Frankfurt, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.|German Cancer Consortium (DKTK), partner site: Frankfurt a. M., Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Rödel
authors.affiliation: Department of Radiation Oncology, University Hospital, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590, Frankfurt, Germany. panagiotis.balermpas@kgu.de.|German Cancer Research Center (DKFZ), Heidelberg, Germany. panagiotis.balermpas@kgu.de.|German Cancer Consortium (DKTK), partner site: Frankfurt a. M., Germany. panagiotis.balermpas@kgu.de.
authors.forename: Panagiotis
authors.identifier: http://orcid.org/0000-0001-5261-6446
authors.initials: P
authors.lastname: Balermpas
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism* / Q000556:secondary*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000556:secondary*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000175:diagnosis* / Q000378:metabolism* / Q000532:radiotherapy; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000077195:Squamous Cell Carcinoma of Head and Neck; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: CUP; Head and neck cancer; Lymph nodes; Neoplasms, unknown primary; Squamous cell carcinoma