title: Stromal infiltration of CD8 T cells is associated with improved clinical outcome in HPV-positive oropharyngeal squamous carcinoma.
abstract: BACKGROUND
  Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) have a better prognosis than those with HPV-negative tumours. There is interest in de-escalating their treatment but strategies are needed for risk stratification to identify subsets with a poor prognosis. This study investigated tumour-infiltrating lymphocytes (TILs) in relation to HPV tumour status and patient survival.
  
  
  METHODS
  Biopsies from 218 patients diagnosed with OPSCC between 2002 and 2011, who underwent chemo/radiotherapy were analysed for HPV by PCR, in-situ hybridisation and p16 immunohistochemistry (IHC). One hundred and thirty-nine samples with concordant HPV detection were analysed for CD3, CD4, CD8 and FoxP3 expression in tumour and stromal regions using multiplexIHC and multispectral image analysis. Labelling of smooth muscle actin (SMA) identified activated stroma.
  
  
  RESULTS
  Human papillomavirus-positive compared with HPV-negative OPSCC had higher infiltration in both tumour and stromal areas of CD4 and CD8 T cells but not FoxP3 T regulatory cells. Only CD3+CD8+ stromal and not tumour area infiltration was associated with increased survival (P=0.02). There was significantly higher SMA expression in HPV-positive compared with -negative tumours, which did not correlate with survival.
  
  
  CONCLUSIONS
  Studies of TILs for risk stratification in OPSCC should assess stromal infiltration.
authors: Translational Radiobiology Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester, Wilmslow Road, Manchester, UK.|The Christie NHS Foundation Trust, Manchester, Wilmslow Road, UK.
authors: K
authors: K
authors: Oguejiofor
authors: Lymphoma Translational Research Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester, Wilmslow Road, Manchester, UK.
authors: J
authors: J
authors: Hall
authors: Lymphoma Translational Research Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, Manchester Medical School, University of Manchester, Wilmslow Road, Manchester, UK.
authors: C
authors: C
authors: Slater
authors: Central Manchester University Hospitals, Manchester, UK.
authors: G
authors: G
authors: Betts
authors: Central Manchester University Hospitals, Manchester, UK.
authors: G
authors: G
authors: Hall
authors: The Christie NHS Foundation Trust, Manchester, Wilmslow Road, UK.
authors: N
authors: N
authors: Slevin
authors: Targeted Therapy Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, the University of Manchester; Wilmslow Road, Manchester.
authors: S
authors: S
authors: Dovedi
authors: Center for Women's Cancer, Institute of Cancer Sciences, University of Manchester, Paterson Building, Wilmslow Road, Manchester, M20 4BX, UK.
authors: P L
authors: PL
authors: Stern
authors: Translational Radiobiology Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester, Wilmslow Road, Manchester, UK.|The Christie NHS Foundation Trust, Manchester, Wilmslow Road, UK.
authors: C M L
authors: CM
authors: West
mesh_terms: D000199:Actins / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D001706:Biopsy; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000821:virology*; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016131:Lymphocyte Subsets / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D009130:Muscle, Smooth / Q000737:chemistry; D009959:Oropharyngeal Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000821:virology*; D009960:Oropharynx / Q000276:immunology / Q000473:pathology; D027383:Papillomaviridae / Q000302:isolation & purification*; D011379:Prognosis
chemical_list: D000199:Actins; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors