Prognostic value of combined CD8 score versus compartmental distribution in head and neck squamous cell carcinoma

Abstract Background The prognostic value of CD8 + T-cell spatial distribution within the tumor microenvironment of head and neck squamous cell carcinoma (HNSCC) remains unclear. We investigated whether the ratio of CD8 + density in the tumor center to the invasion front predicts survival and compared this with total CD8 + density. Methods We analyzed 709 HNSCC patients from the public HANCOCK dataset with tissue microarray-based CD8 + quantification at both the tumor center and the invasion front. Center-to-front CD8 + ratios were calculated and categorized into tertiles. Total CD8 + density (center + front) was also analyzed. Kaplan-Meier, log-rank, and Cox proportional hazards models were used for survival analysis, adjusting for age, HPV status, nodal status, and pT stage. Results Median CD8 + density did not differ between tumor center (393.9 cells/mm²) and invasion front (344.1 cells/mm², p = 0.828). No significant survival difference was observed among ratio tertiles (log-rank Low vs High: p = 0.477; multivariate HR = 1.17, 95% CI: 0.87–1.57, p = 0.300). In contrast, higher total CD8 + density was modestly but statistically significantly associated with improved survival (HR = 0.99 per 100 cells/mm², 95% CI: 0.97-1.00, p = 0.033). Established prognostic factors were confirmed: age (HR = 1.03, p < 0.001), HPV positivity (HR = 0.52, p = 0.006), nodal positivity (HR = 1.72, p = 0.002), and pT3-4 stage (HR = 1.92, p < 0.001). Conclusions The center-to-front CD8 + ratio has limited prognostic value in HNSCC. However, higher total CD8 + density is associated with improved survival, suggesting that overall immune burden, rather than topographic distribution, drives clinical outcomes. These findings suggest that overall CD8 + immune burden may be more informative than spatial distribution for prognostic assessment in HNSCC