OP027: Tumour infiltrating lymphocytes predict survival in HPV-positive OPSCC

Abstract

HPV is now recognised as the major cause of oropharyngeal squamous cell carcinoma (OPSCC). Patients with HPV-positive OPSCC have improved survival compared to those with HPV-negative tumours. One explanation for this may be an immune response against HPV-specific antigens. The aim of this study was to examine levels of tumour-infiltrating lymphocytes (TILs) in HPV-positive and HPV-negative OPSCC, and to establish the effect of TIL-levels on survival. We performed a retrospective analysis of 274 consecutively treated OPSCC patients with complete survival data and archival pathological material. Tissue microarrays were constructed and HPV-status established using a combination of p16 immunohistochemistry and HPV in situ hybridisation. All tumours were assessed for the presence of TILs on H&E sections, and were graded as TIL low (prominent infiltrate in <20% of tumour), TIL moderate (20–80%) or TIL high (>80%). HPV-status and TIL-levels were correlated by cross-tabulation and chi-squared test, and the effect of HPV-status and TIL-levels on disease specific survival (DSS) established using both Kaplan–Meier and Cox-proportional regression analysis. HPV-status was established for 270 tumours, of which 149 (54.4%) were positive. TIL-levels significantly correlated with HPV-status (HPV-positive: TIL low 15%, TIL mod 36%, TIL high 49%; HPV-negative: TIL low 46.3%, TIL mod 38%, TIL high 15.7%; p < 0.001). Both HPV-status and TIL-level were significant predictors of DSS (multivariate analysis: HPV-positive HR 0.40, p = 0.002; TIL high HR 0.24, p < 0.001). TIL-levels stratified survival in HPV-positive tumours; patients with HPV-positive TIL low tumours did not differ in DSS from patients with HPV-negative tumours (multivariate analysis: HPV-positive/TIL low HR 0.99, p = 0.99). HPV-positive tumours are associated with higher levels of TILs than HPV-negative tumours. Patients with HPV-positive tumours containing low numbers of TILs have comparable survival to patients with HPV-negative disease. These data suggest that the reason for improved survival in HPV-positive patients is related to an anti-tumour immune response.