RESUMO
PURPOSE: Human papillomavirus (HPV) infection has been recognized as a cause of head and neck squamous cell carcinomas (HNSCC). Laryngeal squamous cell carcinoma (LSCC) is one of the most common pathologic types of HNSCC. Clinical trials show that there are differences in response to immunotherapy according to HPV status. It was reported that a high level of programmed cell death-ligand 1 (PD-L1) is correlated with better survival in HPV-positive head and neck cancer. In this study, we investigated the expression of PD-L1 in HPV-positive and HPV-negative LSCC to determine its prevalence and prognostic value. METHODS: 52 cases of LSCC were collected from Tangshan Head and Neck Disease Pathology Research Base. PCR-reverse dot blot hybridization and RNAscope in situ hybridization were used to detect HPV status. PD-L1 expression was evaluated by immunohistochemistry and all cases were followed up for survival. SPSS24.0 was used for data entry and statistical analysis. Kaplan-Meier method and Log-rank time series analysis were used for single factor analysis. Multivariate analysis was performed using Cox proportional hazard regression model, and HR and 95% CI were calculated. RESULTS: Of the 52 LSCC patients, 32.7% (17/52) were HPV-positive by RNAscope in situ hybridization, and 51.9% (27/52) of patients were positive for PD-L1 expression by immunohistochemistry. Regression analysis showed that with a median follow-up period of 69 months, smoking and late stage were associated with poor overall survival (OS), whereas HPV positivity and PD-L1 expression showed a better overall survival outcome. CONCLUSION: Smoking status, tumor stage, HPV status, and PD-L1 expression in tumor cells may represent useful prognostic biomarkers in patients with LSCC.
RESUMO
High risk human papillomavirus (HPV) infection is related to the development of head and neck squamous cell carcinoma (HNSCC). Oropharyngeal squamous cell carcinoma (OPSCC) is a common type of HNSCC, and its incidence has increased significantly in recent years. In this study, high risk HPV, the expression of P53, P21, and Cdc2 in OPSCC tissues was detected and the prognostic factors and clinical value of OPSCC were discussed. According to the WHO classification and diagnosis standard for head and neck tumors (2017 Edition), 49 OPSCC cases with complete clinical data were collected from Tangshan Head and Neck Disease Pathology Research Base from January 1, 2012 to December 31, 2018. The E6 and E7 mRNA of HPV 16 and HPV 18 were detected by RNAscope in situ hybridization. The expression of P53, P21, and Cdc2 protein was observed by SP immunohistochemical method and all cases were followed up for survival. Median survival time was analyzed by Kaplan-Meier method. The Log-rank test was used for single factor analysis and Cox regression model was used to analyze multiple prognostic factors. In 49 OPSCC cases the median age was 53 years; 14 were HPV-DNA positive (14/49, 28.6%) while 35 were negative (35/49, 71.4%). E6, E7 mRNA test showed that 20 cases (20/49, 40.8%) were positive for HPV-16. Among them 11 cases were positive for HPV-16 DNA. 2 cases were positive for HPV-18 mRNA (2/49, 4.08%). 27 cases were negative for mRNA16 and 18 (27/49, 55.1%). The prevalence of HPV was 68.8% (11/16) in the non-smoking group, which was higher than that of the smoking group (10/33, 33.3%), (χ2=5.463, P=0.019). There was no significant correlation between HPV detection and gender, age, drinking, tumor differentiation degree, and clinical stage (P > 0.05). The expression rates of P53, P21, and Cdc2 in OPSCC tissues were 63.3% (31/49), 65.3% (32/49), and 67.3% (33/49), respectively. There was no significant correlation between expression of all the three proteins and gender, age, HPV, smoking, drinking, tumor differentiation, and clinical stage (P > 0.05). Cox multifactor regression analysis showed that HPV (HR=0.275, 95% CI: 0.146-0.517), tumor differentiation (HR=1.751, 95% CI: 1.231-2.492), stage (HR=3.268, 95% CI: 1.758-6.074) and expression of Cdc2 protein (HR=1.804, 95% CI: 0.990-3.286) were related to the survival time of patients (P < 0.05). Our findings support that most of the HPV-positive OPSSC patients were non-smokers. The patients with negative HPV, low differentiation, late stage, and Cdc2 positive expression have poor prognosis and need to be followed up.
RESUMO
The aim of this study was to explore the correlation between HPV infection, p53, p16, epidermal growth factor receptor (EGFR), p34cdc2 protein expression and prognosis in patients with adenoid cystic carcinoma of salivary gland. Totally 78 cases of adenoid cystic carcinoma of salivary gland specimens were selected from January 1, 2004 to December 31, 2013 in Tangshan Union Hospital. PCR-reverse dot blot hybridization was used to detect infection of human papilloma virus (HPV), and SP immunohistochemical method was adopted to detect the expression of p53, p16, EGFR and p34cdc2 protein in the carcinoma tissues. Clinical data were collected and the patients were followed up. Results showed that the infection rate of HPV in adenoid cystic carcinoma tissues was 0% (0/78). The expression rate of p53, p16, EGFR and p34cdc2 protein in carcinoma tissues were 75.6% (59/78), 57.7% (45/78), 60.1% (47/78) and 64.1% (50/78), respectively. Expression of p53, p16, EGFR and p34cdc2 proteins was not significantly correlated with patients' age, gender, disease location, TNM classification and histological type (P > 0.05). Kaplan-Meier analysis showed that EGFR-positive patients had a lower median overall survival than EGFR-negative ones (58 months vs. 75 months, respectively. P = 0.001). The result of median progression-free survival was virtually the same for both EGFR-positive and EGFR-negative patients (43 months vs. 49 months, respectively. P = 0.002). p34cdc2-positive patients had a lower median overall survival than p34cdc2-negative ones (61 months vs. 71 months, respectively. P = 0.027). Median progression-free survival was also almost the same for both p34cdc2-positive and p34cdc2-negative patients (44 months vs. 51 months, respectively. P = 0.011). Cox regression analysis showed that expression of EGFR and p34cdc2 was independent risk factors for the prognosis of patients with adenoid cystic carcinoma of salivary gland (relative risk = 13.199, 11.466, P < 0.001). In conclusion, HPV infection is not detected in salivary adenoid cystic carcinoma tissues. p53, p16, EGFR and p34cdc2 protein are positively expressed in most salivary adenoid cystic carcinoma tissues. p16 is unsuitable as a surrogate for HPV infection status in patients with adenoid cystic carcinoma of salivary gland. Expression of EGFR and p34cdc2 is independent risk factors in the prognosis of patients with salivary gland adenoid cystic carcinoma. Patients with EGFR or p34cdc2 positive expression should be followed up closely.
