title: CD8+ and CD4+ tumour infiltrating lymphocytes in relation to human papillomavirus status and clinical outcome in tonsillar and base of tongue squamous cell carcinoma.
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+ 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.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Nordfors
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Grün
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tertipis
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ährlund-Richter
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Linnea
authors.initials: L
authors.lastname: Haeggblom
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Sivars
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tommy
authors.initials: T
authors.lastname: Nyberg
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Marklund
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Munck-Wikland
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Näsman
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Ramqvist
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. Electronic address: Tina.Dalianis@ki.se.
authors.forename: Tina
authors.initials: T
authors.lastname: Dalianis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy / Q000821:virology; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy / Q000821:virology; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000276:immunology / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology; D010865:Pilot Projects; D000077195:Squamous Cell Carcinoma of Head and Neck; D014062:Tongue Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy / Q000821:virology; D014067:Tonsillar Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy / Q000821:virology; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor