Research Information System
Thesis Type: Expertise In Medicine
Institution Of The Thesis: Gazi Üniversitesi, Tıp Fakültesi, Turkey
Approval Date: 2020
Thesis Language: Turkish
Student: AĞAH YENİÇERİ
Supervisor: MEHMET DÜZLÜ
Open Archive Collection: AVESIS Open Access Collection
Abstract:Human Papilloma Virus (HPV) related head and neck squamous cell carcinomas (HNSCC), especially oropharyngeal cancers, are increasing in western countries. Patients with HPV positive HNSCC have different clinical features and generally show better survival than HPV negative HNSCC. HNSCC is considered an immunosuppressive disease. Various mechanisms have been proposed, such as PD1: PD-L1 immune control point pathway, for tumor cells to escape from the immune system. In our study, we investigated p16, HPV DNA and PD-L1 expression levels, correlation between these biomarkers and prognostic values on survival in patients with oral cavity and oropharyngeal squamous cell carcinoma. 73 patients with oral cavity and oropharyngeal squamous cell carcinoma were included in the study. P16 and PD-L1 expression by immunohistochemistry (IHC), HPV 16 DNA expressions by chromogen in situ hybridization (CISH) were evaluated. Paraffin-embedded tumor tissues fixed in formaldehyde were stained p16 with Mouse monoclonal antibody (clone E6H4), PD-L1 with Rabbit monoclonal antibody (clone SP142) and HPV DNA with INFORM HPV III Family 16 Probe. P16 positivity was defined as squamous cell ≥10% cytoplasmic or nuclear staining, HPV DNA positivity was squamous cell ≥1% nuclear staining and PD-L1 positivity was a tumoral cell (TH) ≥5% membranous staining. For comparison, PD-L1 tumor cell membranous staining ≥1% and PD-L1 immune cell (IH) ≥5% membranous staining were considered positive, and were also noted. Our average follow-up was 37.2 months. P16 was positive in 45 (61.6%) patients, HPV DNA positive in 12 patients (16.4%) and PD-L1 positive in 21 patients (28.7%). The best predictor of p16 positivity was gender (p = 0.026). There was no significant correlation between HPV DNA and p16 expressions (R: 0.3, P = 0.8). When the cut-off value was 1% and 5%, there was 46.5% and 28.7% TH PD-L1 positivity, respectively. 45 patients (61.6%) had IH PD-L1 positivity. No significant difference in expression of PD-L1 was observed between p16 (-) and p16 (+) tumors (32% vs. 26% p = 0.62). Advanced stage was the only independent factor associated with poor prognosis for overall survival (HR, 0.198; 95% Confidence Interval (CI), 0.057-0.687: p = 0.011). Overall survival (OS) and disease-free survival (DFS) were better in those positive for p16 (p = 0.039). Overall survival was significantly better in HPV DNA negative patients (p = 0.019). There was no significant relationship between tumor and immune cell PD-L1 ratios and overall and disease-free survival (Tumor cell OS p = 0.921, DFS p = 0.624 and Immune cell OS p = 0.430, DFS p = 0.398). In oral cavity and oropharyngeal squamous cell carcinoma patients, p16 expression is a strong prognostic biomarker for survival. More extensive studies are needed to determine the prognostic value of HPV DNA. There is no correlation between HPV DNA, p16 and PD-L1 expressions. Although PD-L1 expression is observed in the majority of patients, PD-L1 has no prognostic value for survival. When the data in the literature and our study are examined, more comprehensive and prospective prospective studies are needed to determine the role of PD-L1 expression as a prognostic or predictive biomarker.