Clinical Significance of Activating Interleukin‐1 Ligands in HPV‐positive and HPV‐negative HNSCCs

Abstract

Interleukin‐1 alpha (IL‐1α) and interleukin‐1 beta (IL‐1β) are cytokines involved in the acute phase immune response and their expression is upregulated in a variety of solid tumors including head and neck squamous cell carcinomas (HNSCCs). Our previous data has shown that IL‐1α in particular is associated with poor prognosis but this has yet to be studied in the context of human papilloma virus (HPV) status. This study is aimed at determining differences in tumor expression and the clinical significance of IL‐1α and IL‐1β in HPV‐positive (HPV+) and HPV‐negative (HPV‐) tumors. Differences in tumor gene expression and the prognostic value of IL‐1α and IL‐1β were determined in HPV+ and HPV− tumors from publically available gene expression datasets. Tissue microarrays (TMAs) containing HPV+ (n=31) and HPV− (n=47) primary and metastatic HNSCCs were analyzed for IL‐1α and IL‐1β expression using immunohistochemical (IHC) staining. HPV status was confirmed using p16 IHC staining and RNAish. We found that both IL‐1α and IL‐1β gene expression were significantly increased in HPV− tumors compared to HPV+ tumors. However, tumor expression (as detected by IHC) of IL‐1α (but not IL‐1β) was significantly increased in HPV− tumors compared to HPV+ tumors. Comparison of matched primary and metastatic tumors revealed a decrease in IL‐1α expression and an increase in IL‐1β in metastatic tumors compared to primary tumors. Lastly, increased IL‐1α gene expression was significantly associated with worse survival in HPV− tumors but not in HPV+ tumors. IL‐1β held no prognostic value in HPV+ or HPV− tumors. Overall IL‐1α expression may possess more prognostic significance in HPV− tumors rather than HPV+ tumors and this work warrants further investigation in larger patient cohorts.