The ratio of CD4/CD8 T-cells in human papillomavirus-positive laryngeal squamous cell carcinoma accounts for improved outcome.

CONCLUSION: Improved prognosis associated with HPV-positive status may depend on lower CD4/CD8 ratio. Th1 CD4(+ )T cells were found to be the major sub-set of T lymphocytes in the HPV positive laryngeal squamous cell carcinoma microenvironment. BACKGROUND: To examine the prognostic significance of human papillomavirus (HPV) status in relation to the ratio of CD4/CD8 in LSCC. METHODS: In this study, 46 LSCC biopsy samples were retrospectively assessed using immunohistochemistry for CD4(+ )and CD8(+ )tumor infiltrating lymphocytes (TILs). HPV status was determined by HPV in situ hybridization (ISH) and p16(INK4A) immunohistochemistry. Of the 46 samples, 21 were evaluated for the expression of IFN-γ and IL-4 by quantitative real-time PCR (qRT-PCR). The influence of HPV status on locoregional tumor control and T-cell sub-sets infiltrating tumor microenvironment were investigated. RESULTS: Nineteen patients (41.3%) were classified as HPV positive, who had improved disease-free survival (28% in reduction, hazard ratio =0.10; 95% CI =0.011-0.938). A direct correlation between the HPV status and the ratio of CD4/CD8 or mean levels of CD8(+ )T cells was observed. Compared with the HPV-negative samples, HPV-positive samples had a higher ratio of IFN-γ/IL-4 (24.43 ± 29.89 vs 3.90 ± 4.03; p = 0.0375).