title: Differential response rates to irradiation among patients with human papillomavirus positive and negative oropharyngeal cancer.
abstract: OBJECTIVE
  To evaluate the responsiveness of human papillomavirus (HPV) -positive and HPV-negative oropharyngeal cancer to intensity-modulated radiotherapy (IMRT), using axial imaging obtained daily during the course of image-guided radiotherapy (IGRT).
  
  
  METHODS
  Observational cohort study with matched-pair analysis of patients irradiated for HPV-positive and HPV-negative oropharygeal cancer.
  
  
  METHODS
  Ten patients treated by IMRT to 70 Gy for locally advanced, HPV-positive squamous cell carcinoma of the oropharynx were matched to one HPV-negative control subject by age, gender, performance status, T-category, tumor location, and the use of concurrent chemotherapy. The gross tumor volume (GTV) was delineated on daily IGRT scans obtained via kilovoltage cone-beam computed tomography (CBCT). Mathematical modeling using fitted mixed-effects repeated measure analysis was performed to quantitatively and descriptively assess the trajectory of tumor regression.
  
  
  RESULTS
  Patients with HPV-positive tumors experienced a more rapid rate of tumor regression between day 1 of IMRT and the beginning of week 2 (-33% Δ GTV) compared to their counterparts with HPV-negative tumors (-10% Δ GTV), which was statistically significant (p<0.001). During this initial period, the average absolute change in GTV was -22.9 cc/week for HPV-positive tumors and -5.9 cc/week for HPV-negative tumors (p<0.001). After week 2 of IMRT, the rates of GTV regression were comparable between the two groups.
  
  
  CONCLUSIONS
  HPV-positive oropharyngeal cancers exhibited an enhanced response to radiation, characterized by a dramatically more rapid initial regression than those with HPV-negative tumors. Implications for treatment de-intensification in the context of future clinical trials and the possible mechanisms underlying this increased radiosensitivity will be discussed.
authors.affiliation: Department of Radiation Oncology, University of California, Davis, Comprehensive Cancer Center, Sacramento, California, USA. allen.chen@ucdmc.ucdavis.edu
authors.forename: Allen M
authors.initials: AM
authors.lastname: Chen
authors.forename: Judy
authors.initials: J
authors.lastname: Li
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Beckett
authors.forename: Talia
authors.initials: T
authors.lastname: Zhara
authors.forename: Gregory
authors.initials: G
authors.lastname: Farwell
authors.forename: Derick H
authors.initials: DH
authors.lastname: Lau
authors.forename: Regina
authors.initials: R
authors.lastname: Gandour-Edwards
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Vaughan
authors.forename: James A
authors.initials: JA
authors.lastname: Purdy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy* / Q000821:virology; D015331:Cohort Studies; D054893:Cone-Beam Computed Tomography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000532:radiotherapy* / Q000821:virology; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000000981:diagnostic imaging* / Q000473:pathology; D061089:Radiotherapy, Image-Guided; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D016896:Treatment Outcome