Tumor infiltrating lymphocytes (TILs) are thought to represent a host immune response directed against tumour cells. Preclinical and clinical data have shown the presence of TILs to be associated with improved outcomes in many solid tumors including ovarian, colorectal, melanoma and breast. The role of TILS in head and neck cancer (HNC), and their association with Human Papilloma Virus (HPV) status, has not been well studied to date. We set out to characterise the prevalence and tumoral location of TILS in formalin fixed paraffin embedded tissue sections from two independent clinically annotated cohorts of HNC and correlate our findings with clinicopathological features and patient outcomes. Immunohistochemistry was performed for CD3 (T lymphocytes), CD8 (cytotoxic T cells) and FoxP3 (T regulatory cells) on whole sections from cohorts of 113 laryngeal squamous cell carcinomas (LSCC) and 24 oropharyngeal squamous cell carcinomas (OSCC). TIL prevalence was scored semi-quantitatively in two compartments; intra-tumoral (within the tumor nest) and peri-tumoral (located within the stroma surrounding the tumor nests). We found a significant increase in the prevalence of CD3+, CD8+ and FoxP3+ TILs within the tumor nests in OSCC compared to LSCC and an increase in CD3+ TILs in the peri-tumoral area. When stratified by HPV status, we found a significant increase in CD3+, CD8+ and FoxP3+ TILs in both the intra-tumoral and peri-tumoral areas studied in HPV positive OSCC compared to OSCC HPV negative and LSCC HPV negative tumors. Within the LSCC cohort, individual TILs did not correlate with any clinicopathological features, nor have any association with patient outcome. We are yet to analyse the associations with outcome in the OSCC cohort (to be presented at conference). These results suggest that the presence of TILs in HNC may be subsite specific and that there may be a significant role for TIL’s in HPV associated OSCC.