title: Comparison of outcomes of locoregionally advanced oropharyngeal and non-oropharyngeal squamous cell carcinoma over two decades.
abstract: BACKGROUND
  Human papillomavirus (HPV) has emerged as a causative agent and positive prognostic factor for oropharyngeal (OP) head and neck squamous cell cancer (HNSCC). This prompts inquiry into whether therapy improvements or increasing incidence of HPV drives the apparent improvements in HNSCC outcomes observed in non-randomized clinical trials.
  
  
  METHODS
  We reviewed all locoregionally advanced HNSCC patients treated with chemotherapy and radiation in prospective institutional trials at a single institution. Patients were divided into three groups (1, 2, 3) according to treatment time period (1993-1998, 1999-2003, 2004-2010, respectively). We reasoned that if a favorable trend was observed over time in OP but not non-OP patients, HPV status may be confounding treatment effects, whereas this would be unlikely if both subgroups improved over time.
  
  
  RESULTS
  Four hundred and twenty-two patients were identified with OP (55.7%) and non-OP (44.3%) HNSCC. Five-year OP overall survival (OS) improved from 42.3% (group 1) to 72.5% (group 2), and 78.4% (group 3), adjusted P = 0.0084. Non-OP 5-year OS was 51.0% (group 1), 58.8% (group 2), and 66.3% (group 3), adjusted P = 0.51. Five-year recurrence-free survival (RFS) improved for OP groups from 42.3% to 68.4% to 75.8% (adjusted P = 0.017). Non-OP 5-year RFS was 42.9%, 53.6%, and 61.7% for sequential groups (adjusted P = 0.30). Five-year OP distant failure-free survival (DFFS) improved from 42.3% to 71.1% to 77.8% (adjusted P = 0.011). Five-year non-OP DFFS was 46.9%, 57.1%, and 66.0% for sequential groups (adjusted P = 0.38).
  
  
  CONCLUSIONS
  Over the past two decades, OP HNSCC outcomes improved significantly, while non-OP outcomes only trended toward improvement. Although our patients are not stratified by HPV status, improving OP outcomes are likely at least partly due to the increasing HPV incidence. These data further justify trial stratification by HPV status, investigations of novel approaches for carcinogen-related HNSCC, and current de-intensification for HPV-related HNSCC.
authors.affiliation: Department of Radiation and Cellular Oncology. Electronic address: lherman@radonc.uchicago.edu.
authors.forename: L C
authors.initials: LC
authors.lastname: Das
authors.affiliation: Department of Health Studies.
authors.forename: T G
authors.initials: TG
authors.lastname: Karrison
authors.affiliation: Department of Radiation and Cellular Oncology.
authors.forename: M E
authors.initials: ME
authors.lastname: Witt
authors.affiliation: Department of Medicine, University of Chicago Medical Center, Chicago.
authors.forename: C
authors.initials: C
authors.lastname: Muller
authors.affiliation: Department of Otolaryngology, Rush University Medical Center, Chicago.
authors.forename: K
authors.initials: K
authors.lastname: Stenson
authors.affiliation: Department of Otolaryngology, University of Chicago Medical Center, Chicago; The University of Chicago Medicine Comprehensive Cancer Center, Chicago.
authors.forename: E A
authors.initials: EA
authors.lastname: Blair
authors.affiliation: Moores Cancer Center, University of California San Diego, La Jolla, USA.
authors.forename: E E W
authors.initials: EEW
authors.lastname: Cohen
authors.affiliation: Department of Medicine, University of Chicago Medical Center, Chicago; The University of Chicago Medicine Comprehensive Cancer Center, Chicago.
authors.forename: T Y
authors.initials: TY
authors.lastname: Seiwert
authors.affiliation: Department of Radiation and Cellular Oncology; The University of Chicago Medicine Comprehensive Cancer Center, Chicago.
authors.forename: D J
authors.initials: DJ
authors.lastname: Haraf
authors.affiliation: Department of Medicine, University of Chicago Medical Center, Chicago; The University of Chicago Medicine Comprehensive Cancer Center, Chicago.
authors.forename: E E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000821:virology; D005260:Female; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality; D009959:Oropharyngeal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000821:virology; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000453:epidemiology*; D011446:Prospective Studies; D011859:Radiography; D012907:Smoking; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome
keywords: HPV; head and neck; oropharyngeal; squamous cell carcinoma