CD8+ and CD4+ tumour infiltrating lymphocytes in relation to human papillomavirus status and clinical outcome in tonsillar and base of tongue squamous cell carcinoma

Eur J Cancer. 2013 Jul;49(11):2522-30. doi: 10.1016/j.ejca.2013.03.019. Epub 2013 Apr 6.


Patients with human papillomavirus (HPV) positive tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC, respectively) have a better clinical outcome than those with HPV negative tumours, irrespective of treatment. However, to better individualise treatment, additional biomarkers are needed together with HPV status. In a pilot study, we showed that high numbers of CD8(+) tumour infiltrating lymphocytes (TILs) in HPVDNA+ p16(INK4a+) TSCC indicated a better outcome. Here this study was extended. Totally 203 TSCC and 77 BOTSCC formalin fixed paraffin embedded tumour biopsies, earlier tested for HPV DNA (79% HPVDNA+) and p16(INK4a) from patients treated with curative intention, were analysed for CD8(+) and CD4(+) TILs by immunohistochemistry. Data obtained for 275 patients were correlated to HPVDNA and p16(INK4a) status, overall survival (OS) and disease free survival (DFS). In both HPVDNA+ and HPVDNA+ p16(INK4a+) tumours higher CD8(+) TIL counts correlated to a better 3-year OS (logrank test, both p<0.001) and 3-year DFS (logrank test, p = 0.003 and p = 0.004 respectively) as compared to the lowest quartile in the groups. A similar pattern was observed when analysing TSCC alone, while for BOTSCC significance was obtained only for 3-year OS. In HPVDNA- tumours the trend was similar, but significance was obtained again only for 3-year OS. The number of CD4(+) TILs did not generally correlate to survival. In conclusion, in HPVDNA+ and/or HPVDNA+ p16(INK4a+) tumours high CD8(+) TIL counts indicated a better 3-year OS. This suggests that high CD8(+) TIL counts together with HPVDNA+ or HPVDNA+ p16(INK4a+) could be used when selecting patients for more individualised treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Carcinoma, Squamous Cell / virology
  • Female
  • Head and Neck Neoplasms / immunology*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / therapy
  • Head and Neck Neoplasms / virology
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Middle Aged
  • Papillomaviridae / immunology
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / immunology*
  • Papillomavirus Infections / virology
  • Pilot Projects
  • Squamous Cell Carcinoma of Head and Neck
  • Tongue Neoplasms / immunology*
  • Tongue Neoplasms / pathology
  • Tongue Neoplasms / therapy
  • Tongue Neoplasms / virology
  • Tonsillar Neoplasms / immunology*
  • Tonsillar Neoplasms / pathology
  • Tonsillar Neoplasms / therapy
  • Tonsillar Neoplasms / virology
  • Treatment Outcome


  • Biomarkers, Tumor