title: Temporal nodal regression and regional control after primary radiation therapy for N2-N3 head-and-neck cancer stratified by HPV status.
abstract: OBJECTIVE
  To compare the temporal lymph node (LN) regression and regional control (RC) after primary chemoradiation therapy/radiation therapy in human papillomavirus-related [HPV(+)] versus human papillomavirus-unrelated [HPV(-)] head-and-neck cancer (HNC).
  
  
  METHODS
  All cases of N2-N3 HNC treated with radiation therapy/chemoradiation therapy between 2003 and 2009 were reviewed. Human papillomavirus status was ascertained by p16 staining on all available oropharyngeal cancers. Larynx/hypopharynx cancers were considered HPV(-). Initial radiologic complete nodal response (CR) (≤1.0 cm 8-12 weeks after treatment), ultimate LN resolution, and RC were compared between HPV(+) and HPV(-) HNC. Multivariate analysis identified outcome predictors.
  
  
  RESULTS
  A total of 257 HPV(+) and 236 HPV(-) HNCs were identified. The initial LN size was larger (mean, 2.9 cm vs 2.5 cm; P<.01) with a higher proportion of cystic LNs (38% vs 6%, P<.01) in HPV(+) versus HPV(-) HNC. CR was achieved is 125 HPV(+) HNCs (49%) and 129 HPV(-) HNCs (55%) (P=.18). The mean post treatment largest LN was 36% of the original size in the HPV(+) group and 41% in the HPV(-) group (P<.01). The actuarial LN resolution was similar in the HPV(+) and HPV(-) groups at 12 weeks (42% and 43%, respectively), but it was higher in the HPV(+) group than in the HPV(-) group at 36 weeks (90% vs 77%, P<.01). The median follow-up period was 3.6 years. The 3-year RC rate was higher in the HPV(-) CR cases versus non-CR cases (92% vs 63%, P<.01) but was not different in the HPV(+) CR cases versus non-CR cases (98% vs 92%, P=.14). On multivariate analysis, HPV(+) status predicted ultimate LN resolution (odds ratio, 1.4 [95% confidence interval, 1.1-1.7]; P<.01) and RC (hazard ratio, 0.3 [95% confidence interval 0.2-0.6]; P<.01).
  
  
  CONCLUSIONS
  HPV(+) LNs involute more quickly than HPV(-) LNs but undergo a more prolonged process to eventual CR beyond the time of initial assessment at 8 to 12 weeks after treatment. Post radiation neck dissection is advisable for all non-CR HPV(-)/non-CR N3 HPV(+) cases, but it may be avoided for selected non-CR N2 HPV(+) cases with a significant LN involution if they can undergo continued imaging surveillance. The role of positron emission tomography for response assessment should be investigated.
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre/University of Toronto, Toronto, Ontario, Canada.
authors.forename: Shao Hui
authors.initials: SH
authors.lastname: Huang
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Helen
authors.initials: H
authors.lastname: Zhao
authors.forename: Duo-duo
authors.initials: DD
authors.lastname: Chen
authors.forename: Jolie
authors.initials: J
authors.lastname: Ringash
authors.forename: Andrew
authors.initials: A
authors.lastname: Hope
authors.forename: Albiruni
authors.initials: A
authors.lastname: Razak
authors.forename: Ralph
authors.initials: R
authors.lastname: Gilbert
authors.forename: Jonathan
authors.initials: J
authors.lastname: Irish
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.forename: Laura A
authors.initials: LA
authors.lastname: Dawson
authors.forename: Andrew
authors.initials: A
authors.lastname: Bayley
authors.forename: B C John
authors.initials: BC
authors.lastname: Cho
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.forename: Patrick
authors.initials: P
authors.lastname: Gullane
authors.forename: Eugene
authors.initials: E
authors.lastname: Yu
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: Waldron
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery / Q000821:virology*; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery / Q000821:virology; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery / Q000821:virology; D008198:Lymph Nodes / Q000473:pathology / Q000528:radiation effects* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D037981:Neck Dissection; D009367:Neoplasm Staging; D009929:Organ Size; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery / Q000821:virology; D030361:Papillomavirus Infections / Q000821:virology*; D012074:Remission Induction / Q000379:methods; D016896:Treatment Outcome