INTRODUCTION: The incidence of advanced oral cavity and oropharyngeal cancers is generally high. Treatment outcomes for patients, especially those unfit for comprehensive cancer treatment, are unsatisfactory. Therefore, the search for factors to predict response to treatment and increase overall survival is underway. OBJECTIVE: This study aimed to analyze the presence of 32 HPV genotypes in tumor samples of 34 patients and the effect of HPV status and RAD51 on overall survival. METHOD: Tumor samples of 34 patients with locally advanced oropharyngeal or oral cavity cancer treated with accelerated radiotherapy in monotherapy were analyzed using reverse hybridization and immunohistochemistry for the presence of HPV and RAD51. Its effect on overall survival was examined. RESULTS: Only two types of HPV were identified-HPV 16 (dominant) and HPV 66 (two samples). The HPV positivity was associated with a borderline insignificant improvement in 2-year (p = 0.083), 5-year (p = 0.159), and overall survival (p = 0.083). Similarly, the RAD51 overexpression was associated with borderline insignificant improvement in 2-year (p = 0.083) and 5-year (p = 0.159) survival. CONCLUSION: We found no statistically significant differences but detected trends toward improvement in the survival of HPV-positive and RAD51 overexpressing patients unfit for surgical treatment or chemotherapy treated with hyperfractionated radiotherapy. The trends, however, indicate that in a larger group of patients, the effects of these two parameters would likely be statistically significant.

• Keywords
• HPV, RAD51, oral cavity cancer, oropharyngeal cancer, radiotherapy,
• MeSH
• Papillomavirus Infections * complications   MeSH
• Humans MeSH
• Human papillomavirus 6 MeSH
• Oropharyngeal Neoplasms * MeSH
• Prognosis MeSH
• Rad51 Recombinase MeSH
• Carcinoma, Squamous Cell * pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• RAD51 protein, human MeSH Browser
• Rad51 Recombinase MeSH

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death with a 5-year survival of only 21%. Reliable prognostic and/or predictive biomarkers are needed to improve NSCLC patient stratification, particularly in curative disease stages. Since the endogenous cannabinoid system is involved in both carcinogenesis and anticancer immune defense, we hypothesized that tumor tissue expression of cannabinoid 1 and 2 receptors (CB1 and CB2) may affect survival. METHODS: Tumor tissue samples collected from 100 NSCLC patients undergoing radical surgery were analyzed for CB1 and CB2 gene and protein expression using the quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The gene and protein expression data were correlated with disease stage, histology, tumor grading, application of chemotherapy, and survival. Additional paired tumor and normal tissue samples of 10 NSCLC patients were analyzed independently for comparative analysis of CB1 and CB2 gene expression. RESULTS: Patients with tumors expressing the CB2 gene had significantly longer overall survival (OS) (P<0.001), cancer specific survival (CSS) (P=0.002), and disease-free survival (DFS) (P<0.001). They also presented with fewer lymph node metastases at the time of surgery (P=0.011). A multivariate analysis identified CB2 tumor tissue gene expression as a positive prognostic factor for CSS [hazard ratio (HR) =0.274; P=0.013] and DFS (HR =0.322; P=0.009), and increased CSS. High CB2 gene and protein expression were detected in 79.6% and 31.5% of the tested tumor tissue samples, respectively. Neither CB1 gene nor CB1 or CB2 protein expression affected survival. When comparing paired tumor and tumor-free lung tissue samples, we observed reduced CB1 (P=0.008) and CB1 (P=0.056) gene expression in tumor tissues. CONCLUSIONS: In NSCLC patients undergoing radical surgery, expression of the CB1 and CB2 receptor genes is significantly decreased in neoplastic versus tumor-free lung tissue. CB2 tumor tissue gene expression is strongly associated with longer survival (OS, CSS, DFS) and fewer lymph node metastases at the time of surgery. More studies are needed to evaluate its role as a biomarker in NSCLC and to investigate the potential use of CB2 modulators to treat or prevent lung cancers.

• Keywords
• Lung cancer, cannabinoid receptor, cannabinoids, metastasis, patient survival,
• Publication type
• Journal Article MeSH