title: Impact of p16 expression in oropharyngeal cancer in the postoperative setting: the necessity of re-evaluating traditional risk stratification.
abstract: OBJECTIVE
  To evaluate the impact of p16 expression as a surrogate marker of human papillomavirus status in oropharyngeal squamous cell carcinoma patients underwent surgery followed by postoperative radiotherapy.
  
  
  METHODS
  We identified 126 consecutive patients with histologically confirmed, newly diagnosed oropharyngeal squamous cell carcinoma who received surgery followed by radiotherapy and had p16 expression data available. All patients were treated between 2001 and 2011. Patients with high-risk factors (positive surgical margin and/or extracapsular extension) or other risk factors (multiple positive lymph nodes, perineural/lymphovascular invasion) were offered postoperative radiotherapy with or without concurrent chemotherapy.
  
  
  RESULTS
  One hundred and four (82.5%) patients were p16-positive (p16 (+)) and 22 (17.5%) were p16-negative (p16 (-)). With a median follow-up of 56 months, patients with p16 (+) oropharyngeal squamous cell carcinoma exhibited a significantly better 5-year disease-free survival (80.7% vs. 57.6%, P < 0.001) and overall survival (84.9% vs. 59.1%, P < 0.001) than those with p16 (-) tumors. The p16 (+) oropharyngeal squamous cell carcinoma with high-risk factors (n = 64) showed no difference in disease-free survival (79.7% vs. 68.3%; P = 0.531) and overall survival (82.1% vs. 76.2%; P = 0.964) between postoperative radiotherapy and postoperative radiotherapy with concurrent chemotherapy.
  
  
  CONCLUSIONS
  Expression of p16 is a strong independent prognostic factor of survival in the postoperative setting of oropharyngeal squamous cell carcinoma. The favorable prognosis of p16 (+) oropharyngeal squamous cell carcinoma suggests a need to re-examine traditional risk stratification for determining optimal adjuvant treatment.
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul.
authors.forename: Jeongshim
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul.
authors.forename: Jee Suk
authors.initials: JS
authors.lastname: Chang
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul.
authors.forename: Hyung Joo
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul.
authors.forename: Se-Heon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul KCKEUM@yuhs.ac.
authors.forename: Ki Chang
authors.initials: KC
authors.lastname: Keum
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy; D018572:Disease-Free Survival; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy; D030361:Papillomavirus Infections / Q000150:complications / Q000473:pathology / Q000821:virology; D011184:Postoperative Period; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014764:Viral Proteins
keywords: HPV; oropharyngeal squamous cell carcinoma; p16; postoperative setting; risk stratification