Immunohistochemical expression of inflammasome-related proteins in head and neck squamous cell carcinoma tissues-A systematic review.

Abstract

<h4>Background</h4>Inflammasomes are multiprotein complexes that play a crucial role in cancer pathogenesis, including in head and neck squamous cell carcinoma (HNSCC), by regulating inflammation, immune responses, and tumour progression. This systematic review aimed to synthesize current evidence on the immunohistochemical (IHC) expression of inflammasome-related proteins in human HNSCC tissues.<h4>Methodology</h4>A comprehensive search of PubMed, Scopus, Web of Science, LILACS, and Google Scholar was conducted up to 31 May 2025, following PRISMA 2020 guidelines and after prior registration in PROSPERO. Studies were included if they evaluated inflammasome-related proteins, such as NLRP3, ASC, caspase-1, and IL-1β, using IHC in human HNSCC tissues.<h4>Results</h4>Sixteen studies were eligible, with sample sizes ranging from 7 to 176. Risk of bias was assessed using a modified QUIN tool, which revealed some methodological limitations, particularly with scoring consistency, blinding, and antibody validation. NLRP3 was the most consistently overexpressed marker, frequently associated with advanced tumour stage, poor prognosis, and therapy resistance. Other proteins, including IL-1β, ASC, and caspase-1, also demonstrated elevated expression and were linked to inflammation and metastatic features. Gasdermin E was associated with favourable clinical outcomes and improved chemotherapy response. Certainty of evidence, assessed using the GRADE approach, was moderate for NLRP3 but low for other markers. Significant heterogeneity in IHC protocols and a lack of standardized scoring limited cross-study comparability.<h4>Conclusion</h4>Overall, inflammasome-related proteins, especially NLRP3, appear to be key contributors to HNSCC progression and may hold potential as prognostic biomarkers or therapeutic targets.<h4>Systematic review registration</h4>PROSPERO CRD42023453852.