Prognostic Significance of Tumor–Stroma Ratio (TSR) in Head and Neck Squamous Cell Carcinoma: Systematic Review and Meta-Analysis

The management of head and neck squamous cell carcinoma (HNSCC) relies heavily on TNM staging and WHO histologic grading; however, in recent years, the analysis of prognostic markers expressed in the tumor stroma has gained attention. The tumor–stroma ratio (TSR) quantifies the proportion of tumor tissue relative to the surrounding stromal tissue; it is assessed with the percentage of stromal tissue within the tumor area, with a cutoff point of 50% being widely used to discriminate high-stroma cancer. In this systematic review and meta-analysis, we investigated the potential prognostic role of the TSR in HNSCC. After a literature screening, 24 studies dealing with the TSR and survival outcomes were included. The TSR showed a significant association with overall survival (OS) in both unadjusted and adjusted measures (RR 2.04, CI 1.57–2.65, p < 0.01; HR 2.36 CI 1.89–2.94, p < 0.00001), with an even stronger prognostic potential in oral cavity/oral tongue cancers (RR 2.44 CI 1.84–3.22, p < 0.00001). The TSR also showed prognostic value when dealing with cancer-specific survival and was associated with a reduction in disease-free survival (DFS). In particular, the TSR also retained its prognostic role in terms of DFS when specifically considering early-stage cancers in both unadjusted and adjusted analyses (RR 1.81 CI 1.57–2.10, p < 0.00001; HR 2.09 CI 1.58–2.76, p < 0.00001). Therefore, we conclude that the TSR is a reliable prognostic marker that is easy to assess in routine histological slides and can be effectively implemented in the routine evaluation of HNSCC.