title: Correlation of cellular immunity with human papillomavirus 16 status and outcome in patients with advanced oropharyngeal cancer.
abstract: OBJECTIVE
  to determine whether the favorable outcome associated with human papillomavirus (HPV) 16-positive oropharyngeal cancer is related to a patient's adaptive immunity.
  
  
  METHODS
  academic medical center.
  
  
  METHODS
  forty-seven of 66 previously untreated patients (6 of 20 patients with stage III and 41 of 46 with stage IV cancer) in a prospective clinical trial of chemoradiotherapy.
  
  
  METHODS
  all patients were treated with a single course of neoadjuvant chemotherapy followed by either surgery (for nonresponders) or chemoradiotherapy.
  
  
  METHODS
  pretreatment levels (percentages and absolute counts) of CD3, CD4, CD8, natural killer, and B cells and overall white blood cell counts were measured by flow cytometry. Correlations of subsets with HPV-16 status, tumor subsite, cancer stage, T class, N class, smoking status, performance status, sex, response to chemoradiotherapy, p53 mutation type, epidermal growth factor receptor expression, and disease-specific and overall survival were determined.
  
  
  RESULTS
  after a median follow-up of 6.6 years, improved survival was associated with an elevated percentage of CD8 cells (P = .04), a low CD4:CD8 ratio (P = .01), low epidermal growth factor receptor expression (P = .002), and HPV status (P = .02). The percentage of CD8 cells was significantly higher (P = .04) and the CD4:CD8 ratio was significantly lower (P = .02) in HPV-16-positive patients. A higher percentage of CD8 cells was associated with response to induction chemotherapy (P = .02) and complete tumor response after chemoradiotherapy (P = .045).
  
  
  CONCLUSIONS
  these findings confirm previous correlations of outcome with circulating CD8 cell levels and support the conjecture that improved adaptive immunity may play a role in the favorable prognosis of patients with HPV-16-positive cancers.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, 1904 H Taubman, PO Box 5312, Ann Arbor, MI 48109, USA.
authors.forename: Derrick
authors.initials: D
authors.lastname: Wansom
authors.forename: Emily
authors.initials: E
authors.lastname: Light
authors.forename: Frank
authors.initials: F
authors.lastname: Worden
authors.forename: Mark
authors.initials: M
authors.lastname: Prince
authors.forename: Susan
authors.initials: S
authors.lastname: Urba
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Chepeha
authors.forename: Kitrina
authors.initials: K
authors.lastname: Cordell
authors.forename: Avraham
authors.initials: A
authors.lastname: Eisbruch
authors.forename: Jeremy
authors.initials: J
authors.lastname: Taylor
authors.forename: Nisha
authors.initials: N
authors.lastname: D'Silva
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Moyer
authors.forename: Carol R
authors.initials: CR
authors.lastname: Bradford
authors.forename: David
authors.initials: D
authors.lastname: Kurnit
authors.forename: Bhavna
authors.initials: B
authors.lastname: Kumar
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Carey
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wolf
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000276:immunology* / Q000628:therapy; D003131:Combined Modality Therapy; D004279:DNA, Viral / Q000032:analysis*; D005500:Follow-Up Studies; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D007111:Immunity, Cellular; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000150:complications / Q000276:immunology* / Q000628:therapy; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D000970:Antineoplastic Agents; D004279:DNA, Viral