RESUMO
The percentage of head and neck cancer (HNC) positive for human papillomavirus (HPV) is unknown in most parts of India. How toll-like receptors (TLRs) affect the adaptive immune response in HNC is also mainly unknown. We here assessed the expressions of HPV DNA, p16, inflammation, and TLRs in oral squamous cell carcinoma (OC) and oropharyngeal squamous cell carcinoma (OPC). Patients with OC (n = 31) and OPC (n = 41), diagnosed during 2017-2018 at the Malabar Cancer Centre (tertiary cancer center), Kerala, India, were included in the study. Immunohistochemistry was performed on tumor specimens against p16, TLR3, TLR7, TLR8, TLR9, CD4, and CD8. Quantitate polymerase chain reaction for 14 high-risk HPVs (HPV16/18/31/33/35/39/45/51/52/56/58/59/66/68) was performed. Seven out of 31 OC (22.6%) were p16+ but only 3.2% (1/31) of OC were positive for HPV DNA. While 24.4% (10/41) of OPC were p16+, HPV DNA was found in only one P16+ OPC and in no P16- OPC. TLR3, TLR7, TLR8, and TLR9 were expressed both in OC and in OPC. The expression of TLR7 was significantly higher in OPC compared with OC. TLR8 expression was correlated with and TLR7 tended to be correlated with the inflammatory score in OPC (r = 0.56, p < 0.05 and r = 0.52, p = 0.08, respectively). In conclusion, the role of HPV in OC and OPC is minor, and p16 constitutes a poor biomarker for HPV positivity in Kerala, India. Intracellular TLRs are correlated with the degree of inflammation in OPC but not in OC and may potentially constitute a medical target in the therapy of HNC in the future.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Receptor 7 Toll-Like , Receptor Toll-Like 9/metabolismo , Receptor 3 Toll-Like , Papillomavirus Humano 16/genética , Receptor 8 Toll-Like , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/metabolismo , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , DNA , Inflamação , ImunidadeRESUMO
Oral squamous cell carcinoma (OSCC), the most common type of head and neck cancers, is associated with high recurrence, metastasis, low long-term survival rates and poor treatment outcome. As deregulated miRNA expression plays a crucial role in malignant transformation and cancer progression, the present study is aimed at profiling the miRNA expression pattern in OSCC and developing a new miRNA prognostic signature for oral cancer. MiRNA expression profiling was performed using MiRNA microarray in 30 tumor and 18 normal samples. MiRNA signature obtained was validated with quantitative real time PCR (qRT-PCR) in 144 tumor and 36 normal samples. The potential targets, clinical implications and prognostic value of the miRNA signature were elucidated by various bioinformatics and statistical analyses. Microarray profiling identified a set of 105 miRNAs to be differentially expressed in OSCC, out of which a subset of 19 most dysregulated miRNAs were validated by qRT-PCR. In silico analysis revealed the signature miRNAs to be involved in various cancer associated pathways. Up-regulation of miR-196a, miR-21, miR-1237 and downregulation of miR-204, miR-144 was associated with poor prognosis of OSCC patients. The mir-196a/miR-204 expression ratio emerged as best predictor for disease recurrence and patient survival. Altogether, our study identified a miRNA signature for OSCC with prognostic significance.
