title: Deintensification candidate subgroups in human papillomavirus-related oropharyngeal cancer according to minimal risk of distant metastasis.
abstract: OBJECTIVE
  To define human papillomavirus (HPV) -positive oropharyngeal cancers (OPC) suitable for treatment deintensification according to low risk of distant metastasis (DM).
  
  
  METHODS
  OPC treated with radiotherapy (RT) or chemoradiotherapy (CRT) from 2001 to 2009 were included. Outcomes were compared for HPV-positive versus HPV-negative patients. Univariate and multivariate analyses identified outcome predictors. Recursive partitioning analysis (RPA) stratified the DM risk.
  
  
  RESULTS
  HPV status was ascertained in 505 (56%) of 899 consecutive OPCs. Median follow-up was 3.9 years. HPV-positive patients (n = 382), compared with HPV-negative patients (n = 123), had higher local (94% v 80%, respectively, at 3 years; P < .01) and regional control (95% v 82%, respectively; P < .01) but similar distant control (DC; 90% v 86%, respectively; P = .53). Multivariate analysis identified that HPV negativity (hazard ratio [HR], 2.9; 95% CI, 2.0 to 5.0), N2b-N3 (HR, 2.9; 95% CI, 1.8 to 4.9), T4 (HR, 1.8; 95% CI, 1.2 to 2.9), and RT alone (HR, 1.8; 95% CI, 1.1 to 2.5) predicted a lower recurrence-free survival (RFS; all P < .01). Smoking pack-years > 10 reduced overall survival (HR, 1.72; 95% CI, 1.1 to 2.7; P = .03) but did not impact RFS (HR, 1.1; 95% CI, 0.7 to 1.9; P = .65). RPA segregated HPV-positive patients into low (T1-3N0-2c; DC, 93%) and high DM risk (N3 or T4; DC, 76%) groups and HPV-negative patients into different low (T1-2N0-2c; DC, 93%) and high DM risk (T3-4N3; DC, 72%) groups. The DC rates for HPV-positive, low-risk N0-2a or less than 10 pack-year N2b patients were similar for RT alone and CRT, but the rate was lower in the N2c subset managed by RT alone (73% v 92% for CRT; P = .02).
  
  
  CONCLUSIONS
  HPV-positive T1-3N0-2c patients have a low DM risk, but N2c patients from this group have a reduced DC when treated with RT alone and seem less suited for deintensification strategies that omit chemotherapy.
authors.affiliation: Room 5-624, Princess Margaret Hospital, 610 University Ave, Toronto, Ontario, Canada M5G 2M9. Brian.OSullivan@rmp.uhn.on.ca
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
authors.forename: Shao Hui
authors.initials: SH
authors.lastname: Huang
authors.forename: Lillian L
authors.initials: LL
authors.lastname: Siu
authors.forename: John
authors.initials: J
authors.lastname: Waldron
authors.forename: Helen
authors.initials: H
authors.lastname: Zhao
authors.forename: Bayardo
authors.initials: B
authors.lastname: Perez-Ordonez
authors.forename: Ilan
authors.initials: I
authors.lastname: Weinreb
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.forename: Jolie
authors.initials: J
authors.lastname: Ringash
authors.forename: Andrew
authors.initials: A
authors.lastname: Bayley
authors.forename: Laura A
authors.initials: LA
authors.lastname: Dawson
authors.forename: Andrew
authors.initials: A
authors.lastname: Hope
authors.forename: John
authors.initials: J
authors.lastname: Cho
authors.forename: Jonathan
authors.initials: J
authors.lastname: Irish
authors.forename: Ralph
authors.initials: R
authors.lastname: Gilbert
authors.forename: Patrick
authors.initials: P
authors.lastname: Gullane
authors.forename: Angela
authors.initials: A
authors.lastname: Hui
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liu
authors.forename: Eric
authors.initials: E
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000639:trends; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000517:prevention & control*; D009367:Neoplasm Staging; D016017:Odds Ratio; D009864:Ontario / Q000453:epidemiology; D009959:Oropharyngeal Neoplasms / Q000453:epidemiology / Q000473:pathology* / Q000628:therapy* / Q000821:virology; D030361:Papillomavirus Infections / Q000150:complications* / Q000453:epidemiology / Q000821:virology; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects / Q000639:trends; D018570:Risk Assessment; D012307:Risk Factors; D055502:Secondary Prevention