title: Combined analysis of HPV-DNA, p16 and EGFR expression to predict prognosis in oropharyngeal cancer.
abstract: Molecular prognostic indicators for oropharyngeal squamous cell carcinoma (OSCC), including HPV-DNA detection, epidermal growth factor receptor (EGFR) and p16 expression, have been suggested in the literature, but none of these are currently used in clinical practice. To compare these predictors, 106 newly diagnosed OSCC for the presence of HPV-DNA and expression of p16 and EGFR were analyzed. The 5-year disease-free survival (DFS) and overall survival (OS) were calculated in relation to these markers and a multivariate Cox analysis was performed. Twenty-eight percent of the cases contained oncogenic HPV-DNA and 30% were positive for p16. The p16 expression was highly correlated with the presence of HPV-DNA (p < 0.001). Univariate analysis of the 5-year DFS revealed a significantly better outcome for patients with p16-positive tumors (84% vs. 49%, p = 0.009). EGFR-negative tumors showed a tendency toward a better prognosis in DFS (74% vs. 47%, p = 0.084) and OS (70% vs. 45%, p = 0.100). Remarkable and highly significant was the combination of p16 and EGFR expression status, leading to 5-year DFS of 93% for p16+/EGFR- tumors vs. 39% for p16-/EGFR+ tumors (p = 0.003) and to a 5-year OS of 79% vs. 38%, respectively (p = 0.010). In multivariate analysis p16 remained a highly significant prognostic marker for DFS (p = 0.030) showing a 7.5-fold increased risk for relapse in patients with p16-negative tumors. Our data indicate that p16 expression is the most reliable prognostic marker for OSCC and further might be a surrogate marker for HPV-positive OSCC. HPV+/p16+ tumors tended to have decreased EGFR expression, but using both immunohistological markers has significant prognostic implications.
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University of Cologne, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Reimers
authors.forename: Hans U
authors.initials: HU
authors.lastname: Kasper
authors.forename: Soenke J
authors.initials: SJ
authors.lastname: Weissenborn
authors.forename: Hartmut
authors.initials: H
authors.lastname: Stützer
authors.forename: Simon F
authors.initials: SF
authors.lastname: Preuss
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Hoffmann
authors.forename: Ernst Jan M
authors.initials: EJ
authors.lastname: Speel
authors.forename: Hans P
authors.initials: HP
authors.lastname: Dienes
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Pfister
authors.forename: Orlando
authors.initials: O
authors.lastname: Guntinas-Lichius
authors.forename: Jens P
authors.initials: JP
authors.lastname: Klussmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D004279:DNA, Viral / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics* / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D016133:Polymerase Chain Reaction; D011336:Probability; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D066246:ErbB Receptors