title: Detailed Analysis of Clinicopathologic Factors Demonstrate Distinct Difference in Outcome and Prognostic Factors Between Surgically Treated HPV-Positive and Negative Oropharyngeal Cancer.
abstract: BACKGROUND
  Oropharyngeal cancers (OPC) secondary to human papillomavirus (HPV) infections likely represent a completely different disease compared with conventional head and neck cancers. Our objective was to analyze a surgically treated cohort to determine predictors of outcome in HPV-positive versus HPV-negative patients.
  
  
  METHODS
  HPV positivity was inferred based on p16-immunohistochemistry. Data was available for 201 patients with OPC treated with surgical resection with/without adjuvant radiotherapy between 1985 and 2005. Subsite distribution was: 66 (33 %) tonsil, 46 (23 %) soft palate, and 89 (44 %) tongue base. Patients were classified into low-, intermediate-, and high-risk groups based on p16 status and smoking history. Outcomes stratified by p16 status and risk groups were determined by the Kaplan-Meier method. Factors predictive of outcome were determined by univariate and multivariate analyses.
  
  
  RESULTS
  In this cohort, 30 % had locally advanced disease (pT3/T4) and 71 % had nodal metastasis. The 5-year overall (OS), disease-specific, and recurrence-free survival rates were 60, 76, and 66 %, respectively. There were 22 % low-, 34 % intermediate-, and 44 % high-risk patients. Patients who were p16-positive had better survival compared with p16-negative (OS, 74 vs. 44 %; p < .001). Similarly, low-risk group patients had a better survival compared with intermediate- and high-risk groups (OS, 76, 68, 45 %, respectively, p < .001). Independent predictors of survival in p16-negative patients included margin status, lymphovascular invasion, pN status, and extracapsular spread. In contrast, none of these were predictive in p16-positive patients.
  
  
  CONCLUSIONS
  Surgically treated patients with p16-positive OPC have superior survival compared with p16-negative patients. Outcomes in p16-positive and p16-negative OPC are determined by different prognostic factors supporting the notion that these are very different diseases. These should be incorporated into future clinical trials design.
authors: Department of Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ganlyi@mskcc.org.|Singhealth/Duke-NUS Head and Neck Centre, National Cancer Centre, Singapore, Singapore. ganlyi@mskcc.org.
authors: N Gopalakrishna
authors: NG
authors: Iyer
authors: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Snjezana
authors: S
authors: Dogan
authors: Department of Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Frank
authors: F
authors: Palmer
authors: Department of Otolaryngology-Head and Neck Surgery, Columbia University Medical Center, New York, NY, USA.
authors: Rahmatullah
authors: R
authors: Rahmati
authors: Department of Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Iain J
authors: IJ
authors: Nixon
authors: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Nancy
authors: N
authors: Lee
authors: Department of Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Snehal G
authors: SG
authors: Patel
authors: Department of Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Jatin P
authors: JP
authors: Shah
authors: Department of Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Ian
authors: I
authors: Ganly
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology* / Q000601:surgery / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery / Q000821:virology; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000401:mortality / Q000473:pathology* / Q000601:surgery / Q000821:virology; D010611:Pharyngectomy / Q000401:mortality*; D011379:Prognosis; D015996:Survival Rate