Tumor Infiltration Levels of CD3, Foxp3 (+) Lymphocytes and CD68 Macrophages at Diagnosis Predict 5-Year Disease-Specific Survival in Patients with Oropharynx Squamous Cell Carcinoma

SIMPLE SUMMARY: Head and neck cancer (HNC) is the sixth most common cancer worldwide, with a general prognosis of 50% disease-specific survival (DSS). The subgroup of oropharyngeal (OP) cancers are of interest because HPV infection is one of several causative agents and carries favorable prognosis. Influxes of inflammatory cells into tumors may vary with prognosis. T lymphocytes are important regarding specific immune defense. Within the immune system T regulatory cells (Foxp3 positive) co-governs this process. We have therefore primarily studied levels of Foxp3 (+) cells in malignant tumors from 170 patients related to prognosis of the patients. Higher levels of T lymphocyte Foxp3 (+) cells predicted better 5-year DSS. This case was unique relative to age, gender, TNM stage, and HPV infection; but more so among tumor HPV (+) than HPV (−) patients. The results encourage further study into the use of immune-based therapy in HNC patients. ABSTRACT: Head and neck cancer (HNC) is the sixth most common cancer worldwide. Oropharyngeal (OP) cancers are of special interest because of possible underlying HPV infection which is tied to prognosis. Influxes of inflammatory cells into tumors may vary with prognoses. We wanted to study whether the number of tumor-infiltrating lymphocytes (TIL) and tumor-associated macrophages (TAM) in tumors correlated to HPV status and predicted 5-year disease-specific survival (DSS). Formalin-fixed paraffin-embedded (FFPE) biopsies cut sections from 170 patients treated for OP cancer were stained by immunohistochemistry and evaluated for the number of CD68 (+) TAMs, CD3 (+), and Foxp3 (+) (T regulatory) TILs. From FFPE slides HPV by PCR and p16 by immunohistochemistry were established. From FFPE Hematoxylin-Eosin slides, levels of tumor nuclear polymorphism, tumor invasion, desmoplasia, and inflammation were determined as previously published. Levels of TIL CD3 (+) and TIL Foxp3 (+) were increased among the HPV (+) compared to the HPV (−) patients. High levels of TIL Foxp3 (+) and CD68 (+) macrophages predicted better 5-year DSS. TIL Foxp3 (+) levels predicted independent of age, gender, TNM stage, and HPV infection as well as level of stromal desmoplasia, tumor invasion, and nuclear polymorphism, but more pronounced among tumor HPV (+) than HPV (−) patients.