# Characterization of CD8 + and CD68 + Microenvironment and PDL1 Expression in HPV-related Multiphenotypic Sinonasal Carcinoma

## TL;DR

This study examines immune cell markers and PDL1 in a rare type of nasal cancer linked to HPV, finding that certain immune features may predict better outcomes and potential for immunotherapy.

## Contribution

The study is the first to characterize CD8+, CD68+, and PDL1 expression in HPV-related multiphenotypic sinonasal carcinoma and correlate them with clinical outcomes.

## Key findings

- Higher CD8+ T cell and CD68+ macrophage densities were associated with reduced recurrence risk in HMSC.
- PDL1 positivity correlated with increased CD8+ infiltration and was observed in 44.4% of tumors.
- Older age was linked to lower PDL1 expression and higher recurrence rates in HMSC patients.

## Abstract

To characterize the expression of CD8 + T cells, CD68 + macrophages, and PDL1 in HPV-related multiphenotypic sinonasal carcinoma (HMSC) and evaluate their correlations with clinical outcomes.

This retrospective cross-sectional study analyzed 27 HMSC cases. Clinical and histopathological data were obtained from medical records. Immunohistochemical expression of CD8 and CD68 was assessed quantitatively and qualitatively in stromal and intratumoral compartments. PDL1 expression was evaluated using the Combined Positive Score (CPS). HPV genotyping was performed using the Anyplex II HPV28 assay. Statistical analyses included descriptive statistics, Fisher’s exact test, Chi-square test, Spearman’s correlation, Student’s t-test, Mann-Whitney U test, Kaplan-Meier survival analysis with log-rank test, and Cox proportional hazards models.

The cohort included 15 (55.6%) males and 12 (44.4%) females, with a mean age of 59.5 years. Most patients presented without recurrence (n = 17, 63.0%), lymph node metastasis (n = 22, 81.5%), or distant metastasis (n = 23, 85.2%). HPV-33 was the predominant genotype, detected in 17 cases (63.0%). PDL1 positivity was observed in 12 tumors (44.4%) and correlated with increased CD8 + infiltration (ρ = 0.602, p < 0.01). Higher densities of CD8 + T cells and CD68 + macrophages were associated with reduced recurrence risk. Older age correlated with higher Ki67 index (ρ = 0.452, p < 0.05), lower PDL1 expression (ρ=-0.436, p < 0.05), and increased recurrence. Lymph node and distant metastases were associated with poorer disease-specific survival (p = 0.020 and p = 0.010, respectively).

The immune microenvironment, characterized by CD8 + and CD68 + cell density and PDL1 expression, together with patient age, appears to influence clinical outcomes in HMSC. These findings suggest that a subset of HMSC patients, particularly those with an inflamed tumor microenvironment, may be candidates for PDL1-targeted immunotherapy.

The online version contains supplementary material available at 10.1007/s12105-026-01908-0.