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

• Published in: European journal of cancer (1990) 2013-07, Vol.49 (11), p.2522-2530
• Main Authors: Nordfors, Cecilia, Grün, Nathalie, Tertipis, Nikolaos, Ährlund-Richter, Andreas, Haeggblom, Linnea, Sivars, Lars, Du, Juan, Nyberg, Tommy, Marklund, Linda, Munck-Wikland, Eva, Näsman, Anders, Ramqvist, Torbjörn, Dalianis, Tina
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Base of tongue cancer; Biological and medical sciences; Biomarkers, Tumor - immunology; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; Carcinoma, Squamous Cell - virology; CD4 antigen; CD4+ TILs; CD4-Positive T-Lymphocytes - immunology; CD8+ TILs; CD8-Positive T-Lymphocytes - immunology; Clinical outcome; Female; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - therapy; Head and Neck Neoplasms - virology; Hematology, Oncology and Palliative Medicine; HPV; Human papillomavirus; Humans; Lymphocytes, Tumor-Infiltrating - immunology; Male; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Papillomaviridae - immunology; Papillomaviridae - isolation & purification; Papillomavirus Infections - immunology; Papillomavirus Infections - virology; Pharmacology. Drug treatments; Pilot Projects; Squamous Cell Carcinoma of Head and Neck; Tongue Neoplasms - immunology; Tongue Neoplasms - pathology; Tongue Neoplasms - therapy; Tongue Neoplasms - virology; Tonsillar cancer; Tonsillar Neoplasms - immunology; Tonsillar Neoplasms - pathology; Tonsillar Neoplasms - therapy; Tonsillar Neoplasms - virology; Treatment Outcome; Tumors
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/j.ejca.2013.03.019

Abstract 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+ p16INK4a+ 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 p16INK4a 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 p16INK4a status, overall survival (OS) and disease free survival (DFS). In both HPVDNA+ and HPVDNA+ p16INK4a+ 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+ p16INK4a+ tumours high CD8+ TIL counts indicated a better 3-year OS. This suggests that high CD8+ TIL counts together with HPVDNA+ or HPVDNA+ p16INK4a+ could be used when selecting patients for more individualised treatment.