title: Infiltrating lymphocytes and human papillomavirus-16--associated oropharyngeal cancer.
abstract: OBJECTIVE
  Human papillomavirus-16 (HPV-16)-associated carcinoma of the oropharynx has a favorable prognosis. Such patients have elevated CD8+ T-lymphocyte levels that correlate with response to chemotherapy and survival. Tumor-infiltrating lymphocyte (TIL) subpopulations were assessed in pretreatment biopsies from a prospective patient cohort to determine if TIL subsets differed by HPV status, clinical factors, or patient outcome or correlated with peripheral blood T-cell levels.
  
  
  METHODS
  Retrospective immunological correlative study of patients entered in a prospective Phase 2 clinical trial.
  
  
  METHODS
  Measured were CD8, CD4, CD68, and Treg (FoxP3) lymphocytes by immunohistochemistry in a tissue microarray created from patients (n=46) with advanced oropharyngeal cancer. Correlations with peripheral blood levels, HPV status, expression of epidermal growth factor receptor (EGFR), clinical tumor, and patient characteristics and outcome were determined. Median follow-up was 6.6 years.
  
  
  RESULTS
  HPV-16-positive patients had improved survival (P=.016). Degree of T-cell infiltration did not differ by HPV status but was significantly related to disease-specific survival (DSS) and overall survival (OS). Even after adjusting for HPV status, we found that CD8, FoxP3, and total T cells were significantly associated with DSS (P=.0236, P=.0040, and P=.0197, respectively) and OS (P=.0137, P=.0158, and P=.0115, respectively). Less T-cell infiltration (P=.0130) and CD4 cells in particular (P=.0792) were associated with higher EGFR expression.
  
  
  CONCLUSIONS
  Improved outcomes are associated with increased TILs independent of HPV status and suggest the local immune response may be more related to factors such as tumor size, EGFR expression, or performance status than HPV status. Further study of larger numbers of patients and infiltrates combined with functional analysis of individual subsets may be necessary to detect significant differences in local immunity in HPV-16-related cancers.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Derrick
authors.initials: D
authors.lastname: Wansom
authors.forename: Emily
authors.initials: E
authors.lastname: Light
authors.forename: Dafydd
authors.initials: D
authors.lastname: Thomas
authors.forename: Francis
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
authors.initials: D
authors.lastname: Chepeha
authors.forename: Bhavna
authors.initials: B
authors.lastname: Kumar
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: Jeffrey
authors.initials: J
authors.lastname: Moyer
authors.forename: Carol
authors.initials: C
authors.lastname: Bradford
authors.forename: Nisha
authors.initials: N
authors.lastname: D'Silva
authors.forename: Thomas
authors.initials: T
authors.lastname: Carey
authors.forename: Jonathan
authors.initials: J
authors.lastname: McHugh
authors.forename: Gregory
authors.initials: G
authors.lastname: Wolf
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D052162:Human papillomavirus 16; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000473:pathology* / Q000821:virology*; D030361:Papillomavirus Infections / Q000473:pathology*; D011446:Prospective Studies; D012189:Retrospective Studies