title: Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma.
abstract: OBJECTIVE
  Risk of cancer progression is reduced for patients with human papillomavirus (HPV) -positive oropharynx cancer (OPC) relative to HPV-negative OPC, but it is unknown whether risk of death after progression is similarly reduced.
  
  
  METHODS
  Patients with stage III-IV OPC enrolled onto Radiation Therapy Oncology Group trials 0129 or RTOG 0522 who had known tumor p16 status plus local, regional, and/or distant progression after receiving platinum-based chemoradiotherapy were eligible for a retrospective analysis of the association between tumor p16 status and overall survival (OS) after disease progression. Rates were estimated by Kaplan-Meier method and compared by log-rank; hazard ratios (HRs) were estimated by Cox models. Tests and models were stratified by treatment protocol.
  
  
  RESULTS
  A total of 181 patients with p16-positive (n = 105) or p16-negative (n = 76) OPC were included in the analysis. Patterns of failure and median time to progression (8.2 v 7.3 months; P = .67) were similar for patients with p16-positive and p16-negative tumors. After a median follow-up period of 4.0 years after disease progression, patients with p16-positive OPC had significantly improved survival rates compared with p16-negative patients (2-year OS, 54.6% v 27.6%; median, 2.6 v 0.8 years; P < .001). p16-positive tumor status (HR, 0.48; 95% CI, 0.31 to 0.74) and receipt of salvage surgery (HR, 0.48; 95% CI; 0.27 to 0.84) reduced risk of death after disease progression whereas distant versus locoregional progression (HR, 1.99; 95% CI, 1.28 to 3.09) increased risk, after adjustment for tumor stage and cigarette pack-years at enrollment.
  
  
  CONCLUSIONS
  Tumor HPV status is a strong and independent predictor of OS after disease progression and should be a stratification factor for clinical trials for patients with recurrent or metastatic OPC.
authors: Carole Fakhry, Johns Hopkins Medical Institutions; Milton J. Dance Jr Head and Neck Center, Baltimore, MD; Qiang Zhang, Jonathan Harris, Radiation Therapy Oncology Group Statistical Center; John Andrew Ridge, Fox Chase Cancer Center, Philadelphia, PA; David Rosenthal, Adel El-Naggar, Adam S. Garden, The University of Texas MD Anderson Cancer Center, Houston, TX; Andy Trotti, H. Lee Moffitt Cancer Center, Tampa, FL; Vilija Avizonis, Intermountain Medical Center, Murray, UT; Quynh-Thu Le, Stanford University Medical Center, Stanford, CA; Maura Gillison, Ohio State University Medical Center, Columbus, OH; Phuc Felix Nguyen-Tan, Denis Soulieres, Centre Hospitalier de l'Université de Montréal Hospital Notre Dame, Montreal, Canada. cfakhry@jhmi.edu.
authors: Carole
authors: C
authors: Fakhry
authors: Carole Fakhry, Johns Hopkins Medical Institutions; Milton J. Dance Jr Head and Neck Center, Baltimore, MD; Qiang Zhang, Jonathan Harris, Radiation Therapy Oncology Group Statistical Center; John Andrew Ridge, Fox Chase Cancer Center, Philadelphia, PA; David Rosenthal, Adel El-Naggar, Adam S. Garden, The University of Texas MD Anderson Cancer Center, Houston, TX; Andy Trotti, H. Lee Moffitt Cancer Center, Tampa, FL; Vilija Avizonis, Intermountain Medical Center, Murray, UT; Quynh-Thu Le, Stanford University Medical Center, Stanford, CA; Maura Gillison, Ohio State University Medical Center, Columbus, OH; Phuc Felix Nguyen-Tan, Denis Soulieres, Centre Hospitalier de l'Université de Montréal Hospital Notre Dame, Montreal, Canada.
authors: Qiang
authors: Q
authors: Zhang
authors: Carole Fakhry, Johns Hopkins Medical Institutions; Milton J. Dance Jr Head and Neck Center, Baltimore, MD; Qiang Zhang, Jonathan Harris, Radiation Therapy Oncology Group Statistical Center; John Andrew Ridge, Fox Chase Cancer Center, Philadelphia, PA; David Rosenthal, Adel El-Naggar, Adam S. Garden, The University of Texas MD Anderson Cancer Center, Houston, TX; Andy Trotti, H. Lee Moffitt Cancer Center, Tampa, FL; Vilija Avizonis, Intermountain Medical Center, Murray, UT; Quynh-Thu Le, Stanford University Medical Center, Stanford, CA; Maura Gillison, Ohio State University Medical Center, Columbus, OH; Phuc Felix Nguyen-Tan, Denis Soulieres, Centre Hospitalier de l'Université de Montréal Hospital Notre Dame, Montreal, Canada.
authors: Phuc Felix
authors: PF
authors: Nguyen-Tan
authors: Carole Fakhry, Johns Hopkins Medical Institutions; Milton J. Dance Jr Head and Neck Center, Baltimore, MD; Qiang Zhang, Jonathan Harris, Radiation Therapy Oncology Group Statistical Center; John Andrew Ridge, Fox Chase Cancer Center, Philadelphia, PA; David Rosenthal, Adel El-Naggar, Adam S. Garden, The University of Texas MD Anderson Cancer Center, Houston, TX; Andy Trotti, H. Lee Moffitt Cancer Center, Tampa, FL; Vilija Avizonis, Intermountain Medical Center, Murray, UT; Quynh-Thu Le, Stanford University Medical Center, Stanford, CA; Maura Gillison, Ohio State University Medical Center, Columbus, OH; Phuc Felix Nguyen-Tan, Denis Soulieres, Centre Hospitalier de l'Université de Montréal Hospital Notre Dame, Montreal, Canada.
authors: David
authors: D
authors: Rosenthal
authors: Carole Fakhry, Johns Hopkins Medical Institutions; Milton J. Dance Jr Head and Neck Center, Baltimore, MD; Qiang Zhang, Jonathan Harris, Radiation Therapy Oncology Group Statistical Center; John Andrew Ridge, Fox Chase Cancer Center, Philadelphia, PA; David Rosenthal, Adel El-Naggar, Adam S. Garden, The University of Texas MD Anderson Cancer Center, Houston, TX; Andy Trotti, H. Lee Moffitt Cancer Center, Tampa, FL; Vilija Avizonis, Intermountain Medical Center, Murray, UT; Quynh-Thu Le, Stanford University Medical Center, Stanford, CA; Maura Gillison, Ohio State University Medical Center, Columbus, OH; Phuc Felix Nguyen-Tan, Denis Soulieres, Centre Hospitalier de l'Université de Montréal Hospital Notre Dame, Montreal, Canada.
authors: Adel
authors: A
authors: El-Naggar
authors: Carole Fakhry, Johns Hopkins Medical Institutions; Milton J. Dance Jr Head and Neck Center, Baltimore, MD; Qiang Zhang, Jonathan Harris, Radiation Therapy Oncology Group Statistical Center; John Andrew Ridge, Fox Chase Cancer Center, Philadelphia, PA; David Rosenthal, Adel El-Naggar, Adam S. Garden, The University of Texas MD Anderson Cancer Center, Houston, TX; Andy Trotti, H. Lee Moffitt Cancer Center, Tampa, FL; Vilija Avizonis, Intermountain Medical Center, Murray, UT; Quynh-Thu Le, Stanford University Medical Center, Stanford, CA; Maura Gillison, Ohio State University Medical Center, Columbus, OH; Phuc Felix Nguyen-Tan, Denis Soulieres, Centre Hospitalier de l'Université de Montréal Hospital Notre Dame, Montreal, Canada.
authors: Adam S
authors: AS
authors: Garden
authors: Carole Fakhry, Johns Hopkins Medical Institutions; Milton J. Dance Jr Head and Neck Center, Baltimore, MD; Qiang Zhang, Jonathan Harris, Radiation Therapy Oncology Group Statistical Center; John Andrew Ridge, Fox Chase Cancer Center, Philadelphia, PA; David Rosenthal, Adel El-Naggar, Adam S. Garden, The University of Texas MD Anderson Cancer Center, Houston, TX; Andy Trotti, H. Lee Moffitt Cancer Center, Tampa, FL; Vilija Avizonis, Intermountain Medical Center, Murray, UT; Quynh-Thu Le, Stanford University Medical Center, Stanford, CA; Maura Gillison, Ohio State University Medical Center, Columbus, OH; Phuc Felix Nguyen-Tan, Denis Soulieres, Centre Hospitalier de l'Université de Montréal Hospital Notre Dame, Montreal, Canada.
authors: Denis
authors: D
authors: Soulieres
authors: Carole Fakhry, Johns Hopkins Medical Institutions; Milton J. Dance Jr Head and Neck Center, Baltimore, MD; Qiang Zhang, Jonathan Harris, Radiation Therapy Oncology Group Statistical Center; John Andrew Ridge, Fox Chase Cancer Center, Philadelphia, PA; David Rosenthal, Adel El-Naggar, Adam S. Garden, The University of Texas MD Anderson Cancer Center, Houston, TX; Andy Trotti, H. Lee Moffitt Cancer Center, Tampa, FL; Vilija Avizonis, Intermountain Medical Center, Murray, UT; Quynh-Thu Le, Stanford University Medical Center, Stanford, CA; Maura Gillison, Ohio State University Medical Center, Columbus, OH; Phuc Felix Nguyen-Tan, Denis Soulieres, Centre Hospitalier de l'Université de Montréal Hospital Notre Dame, Montreal, Canada.
authors: Andy
authors: A
authors: Trotti
authors: Carole Fakhry, Johns Hopkins Medical Institutions; Milton J. Dance Jr Head and Neck Center, Baltimore, MD; Qiang Zhang, Jonathan Harris, Radiation Therapy Oncology Group Statistical Center; John Andrew Ridge, Fox Chase Cancer Center, Philadelphia, PA; David Rosenthal, Adel El-Naggar, Adam S. Garden, The University of Texas MD Anderson Cancer Center, Houston, TX; Andy Trotti, H. Lee Moffitt Cancer Center, Tampa, FL; Vilija Avizonis, Intermountain Medical Center, Murray, UT; Quynh-Thu Le, Stanford University Medical Center, Stanford, CA; Maura Gillison, Ohio State University Medical Center, Columbus, OH; Phuc Felix Nguyen-Tan, Denis Soulieres, Centre Hospitalier de l'Université de Montréal Hospital Notre Dame, Montreal, Canada.
authors: Vilija
authors: V
authors: Avizonis
authors: Carole Fakhry, Johns Hopkins Medical Institutions; Milton J. Dance Jr Head and Neck Center, Baltimore, MD; Qiang Zhang, Jonathan Harris, Radiation Therapy Oncology Group Statistical Center; John Andrew Ridge, Fox Chase Cancer Center, Philadelphia, PA; David Rosenthal, Adel El-Naggar, Adam S. Garden, The University of Texas MD Anderson Cancer Center, Houston, TX; Andy Trotti, H. Lee Moffitt Cancer Center, Tampa, FL; Vilija Avizonis, Intermountain Medical Center, Murray, UT; Quynh-Thu Le, Stanford University Medical Center, Stanford, CA; Maura Gillison, Ohio State University Medical Center, Columbus, OH; Phuc Felix Nguyen-Tan, Denis Soulieres, Centre Hospitalier de l'Université de Montréal Hospital Notre Dame, Montreal, Canada.
authors: John Andrew
authors: JA
authors: Ridge
authors: Carole Fakhry, Johns Hopkins Medical Institutions; Milton J. Dance Jr Head and Neck Center, Baltimore, MD; Qiang Zhang, Jonathan Harris, Radiation Therapy Oncology Group Statistical Center; John Andrew Ridge, Fox Chase Cancer Center, Philadelphia, PA; David Rosenthal, Adel El-Naggar, Adam S. Garden, The University of Texas MD Anderson Cancer Center, Houston, TX; Andy Trotti, H. Lee Moffitt Cancer Center, Tampa, FL; Vilija Avizonis, Intermountain Medical Center, Murray, UT; Quynh-Thu Le, Stanford University Medical Center, Stanford, CA; Maura Gillison, Ohio State University Medical Center, Columbus, OH; Phuc Felix Nguyen-Tan, Denis Soulieres, Centre Hospitalier de l'Université de Montréal Hospital Notre Dame, Montreal, Canada.
authors: Jonathan
authors: J
authors: Harris
authors: Carole Fakhry, Johns Hopkins Medical Institutions; Milton J. Dance Jr Head and Neck Center, Baltimore, MD; Qiang Zhang, Jonathan Harris, Radiation Therapy Oncology Group Statistical Center; John Andrew Ridge, Fox Chase Cancer Center, Philadelphia, PA; David Rosenthal, Adel El-Naggar, Adam S. Garden, The University of Texas MD Anderson Cancer Center, Houston, TX; Andy Trotti, H. Lee Moffitt Cancer Center, Tampa, FL; Vilija Avizonis, Intermountain Medical Center, Murray, UT; Quynh-Thu Le, Stanford University Medical Center, Stanford, CA; Maura Gillison, Ohio State University Medical Center, Columbus, OH; Phuc Felix Nguyen-Tan, Denis Soulieres, Centre Hospitalier de l'Université de Montréal Hospital Notre Dame, Montreal, Canada.
authors: Quynh-Thu
authors: QT
authors: Le
authors: Carole Fakhry, Johns Hopkins Medical Institutions; Milton J. Dance Jr Head and Neck Center, Baltimore, MD; Qiang Zhang, Jonathan Harris, Radiation Therapy Oncology Group Statistical Center; John Andrew Ridge, Fox Chase Cancer Center, Philadelphia, PA; David Rosenthal, Adel El-Naggar, Adam S. Garden, The University of Texas MD Anderson Cancer Center, Houston, TX; Andy Trotti, H. Lee Moffitt Cancer Center, Tampa, FL; Vilija Avizonis, Intermountain Medical Center, Murray, UT; Quynh-Thu Le, Stanford University Medical Center, Stanford, CA; Maura Gillison, Ohio State University Medical Center, Columbus, OH; Phuc Felix Nguyen-Tan, Denis Soulieres, Centre Hospitalier de l'Université de Montréal Hospital Notre Dame, Montreal, Canada.
authors: Maura
authors: M
authors: Gillison
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009959:Oropharyngeal Neoplasms / Q000401:mortality / Q000821:virology*; D027383:Papillomaviridae / Q000302:isolation & purification*; D016016:Proportional Hazards Models
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins