ABSTRACT
BACKGROUND/AIM: Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is clinically and immunologically distinct from HPV-negative HNSCC. Herein, we investigated the presence of tumor antigens HPV E6/E7 and wild-type p53-specific T-cell responses, and the impact of immune checkpoint blockade in patients with HPV-positive HNSCC. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) from patients with HPV-positive HNSCC were stimulated with HPV E6/E7 or wild-type p53-derived peptide mixture and evaluated using the interferon-γ enzyme-linked immunosorbent spot assay. Flow cytometry was performed to analyze the proportion of T-cell subsets and T cells expressing immune checkpoint molecules. RESULTS: HPV E6/E7-specific T cells were detected in 22 (95.7%) of 23 patients, whereas wild-type p53-specific T cells were detected in 3 (15.0%) of 20 patients. Seven (43.8%) of 16 patients exhibited wild-type p53-specific T-cell responses, as determined using whole proteins instead of peptides. Immune checkpoint blockade enhanced wild-type p53-specific T-cell responses in 9 (45.0%) of 20 patients. Flow cytometric analysis of PBMCs revealed that responders exhibiting enhanced wild-type p53-specific T-cell responses following immune checkpoint blockade had a significantly higher proportion of Ki-67+CD4+ T cells, Ki-67+CD8+ T cells, regulatory T cells, PD-1+CD4+ T cells, and TIM-3+CD4+ T cells than non-responders. CONCLUSION: Our findings indicate that tumor antigen-specific T cells are present in the peripheral blood of patients with HPV-positive HNSCC. Blockade of checkpoint pathways can enhance T-cell responses in certain patients, probably via activated T cells, Tregs, and/or exhausted CD4+ T cells.
Subject(s)
Head and Neck Neoplasms , Immune Checkpoint Inhibitors , Papillomavirus Infections , Squamous Cell Carcinoma of Head and Neck , Humans , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/virology , Squamous Cell Carcinoma of Head and Neck/drug therapy , Male , Female , Middle Aged , Aged , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/virology , Papillomavirus Infections/immunology , Papillomavirus Infections/virology , Antigens, Neoplasm/immunology , Oncogene Proteins, Viral/immunology , Tumor Suppressor Protein p53/immunology , Adult , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Papillomaviridae/immunology , T-Lymphocytes/immunology , Human Papillomavirus VirusesABSTRACT
We retrospectively analyzed the clinicopathological factors affecting survival in patients with previously untreated parotid carcinoma. The subjects were 50 patients treated in our department from 1987 through 2011. The T stage was T1, T2, T3, and T4 in 4 patients, 11 patients, 9 patients, and 26 patients, respectively. The N stage was N0, N1, and N2 in 36 patients, 3 patients, and 11 patients, respectively. The clinical stage was I, II, III, and IV in 4 patients, 10 patients, 7 patients, and 29 patients, respectively. Histopathologically, eleven tumor types were observed; mucoepidermoid carcinoma was the most common. The overall 5-year survival rate was 72.1%, and the disease-specific 5-year survival rate was 74.0% in 42 patients who received radical surgery. Twelve patients relapsed; the site of relapse was the primary site alone in 2, in the neck alone in 3 patients, in the neck with distant metastases in 2 patients, and in distant metastatic site (s) alone in 5 patients. Univariate analysis showed that significant prognostic factors for overall survival rates were the T stage, cervical lymph node metastasis, clinical stage, grade, facial nerve palsy, and tumor size. We concluded that patients at high risk of recurrence should receive adjuvant therapy to improve the therapeutic outcomes.
Subject(s)
Carcinoma/pathology , Parotid Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma/therapy , Female , Humans , Male , Middle Aged , Parotid Neoplasms/therapy , Prognosis , Retrospective StudiesABSTRACT
OBJECTIVE: To present the first reported case of a simultaneous squamous cell carcinoma with a leiomyosarcoma of the larynx, our treatment of the patient, and the 9-month follow-up results. STUDY DESIGN: Case study. METHODS: Review of diagnostic studies, the operative technique, and the patient's chart for the 9-month period after treatment. RESULTS: A case with double laryngeal tumors with simultaneous evolution but different histological patterns is described. The squamous cell carcinoma and leiomyosarcoma involved both the vocal cords and the anterior commissure. A partial laryngectomy was performed, and the patient has been free of disease for 9 months. CONCLUSIONS: Multiple laryngeal tumors are exceedingly rare. To our knowledge, no previous reports of a simultaneous squamous cell carcinoma and a leiomyosarcoma of the larynx have been reported. Both tumors were not invasive in this case, so conservation surgery was feasible.
