P53 and pRB induction improves response to radiation therapy in HPV-positive laryngeal squamous cell carcinoma.

INTRODUCTION: Patients with Human Papillomavirus (HPV+)-associated Laryngeal Squamous Cell Carcinoma (LSCC) exhibit dramatically improved survival relative to those with HPV-Negative (HPV-) tumors. In this study, the authors aimed to investigate the radiosensitivity of all available confirmed HPV+ and HPV-LSCC cells in vitro and in vivo. METHODS: Primary LSCC cells were generated from tumor specimens obtained from patients. Real-time PCR was performed to confirm HPV infection and the expression of HPV-related genes (E6 and E7), p53, and pRB. Clonogenic survival assays, western blotting, and flow cytometry were used to assess radiation sensitivity, apoptosis, and the expression of p53 and pRB. p53 and pRB knockout cells were generated using CRISPR/Cas9 technology. RESULTS: HPV+ LSCC cells displayed enhanced radiation sensitivity compared to HPV- cells. Radiation-induced apoptosis in HPV+ LSCC cells, accompanied by increased levels of p53 and pRB. Knockout of p53 or pRB led to radiation resistance and attenuated radiation-induced apoptosis in HPV+ LSCC cells. In vivo experiments showed similar results, where knockout of p53 or pRB decreased radiosensitivity in tumor-bearing mice. CONCLUSION: The present findings demonstrated that HPV+ LSCC cells displayed obvious inherent radiation sensitivity, corresponding to increased apoptosis following radiation exposure. Mechanism study showed that the expression of p53 and pRB in HPV+ cells are required for radiation sensitivity. These findings highlight a novel mechanism by which p53 and pRB play key roles in the radiation sensitivity of HPV+ LSCC compared to HPV-LSCC.

Pattern and prognostic value of lymph node metastasis in sinonasal mucosal melanoma.

OBJECTIVE: To analyze the pattern of lymph node (LN) metastasis and its effect on prognosis in sinonasal mucosal melanoma (SNMM). METHODS: This retrospective study was conducted based on the Surveillance, Epidemiology, and End Results (SEER) Program data. Survival outcomes were analyzed using the Kaplan-Meier method. Factors were compared between groups using log-rank test and Fisher's exact test, and prognostic factors were screened using the Cox proportional hazards model. Propensity score matching (PSM) was conducted to examine the treatment differences after accounting for sex, age, race, T stage, N stage, and M stage. RESULTS: Level I (57.1%) and level II (53.6%) nodes were the most common sites of lymph node metastasis, followed by level III (17.9%) and IV (17.9%) nodes. T stage, M stage, and tumor size were associated with LN metastasis. The 5-year overall survival rates for patients without and with LN metastasis were 35.2% and 5.3%, respectively. CONCLUSIONS: Level I and II lymph nodes may be the sentinel nodes of SNMM, Advanced T stage and increasing tumor size could promote LN metastasis. LN metastasis may promote distant metastasis and remains an important prognostic factor for patients with SNMM.

Supraglottic squamous cell carcinomas have distinctive clinical features and prognosis based on subregion.

OBJECTIVE: To analyze the clinicopathologic characteristics and prognosis of patients with squamous cell carcinoma localized to different supraglottic subregions. METHODS: Clinicopathologic data were reviewed retrospectively for 111 patients with supraglottic squamous cell carcinoma who were diagnosed between January 1, 1995 and December 31, 2005 and were initially treated with surgery. DNA from human papillomavirus (HPV) 16 and (or /and) HPV 18 were detected in all the 111 supraglottic carcinoma specimens using in situ hybridization. Survival analysis was performed by Kaplan-Meier analysis, factors were compared using log-rank test, and prognostic factors were determined using Cox proportional hazards model. The relationship between subregions and clinicopathologic factors was analyzed using Chi-square tests. RESULTS: HPV prevalence differed between patients with aryepiglottic fold carcinoma and ventricle carcinoma (P < .05). The local-regional control rates, overall survival rates or cancer specific survival rates were significantly different between different subregions. Univariate analysis indicated that pTNM classification, pN spread, and subregion were associated with prognosis (P < .05). Multivariate analysis indicated that pTNM classification and subregion were associated with supraglottic carcinoma prognosis. The survival rate was better for patients with carcinoma of the epiglottis or ventricular bands compared to those with carcinoma in the aryepiglottic fold or ventricle (P = .012). CONCLUSIONS: Subregion may be a new prognostic factor for supraglottic squamous cell carcinoma. Different supraglottic carcinoma subregions have distinct clinical features such as HPV expression, lymph node metastasis rate, local-regional control and prognosis. Therefore, it is necessary to subdivide supraglottic squamous cell carcinomas into several subregion groups to individualize therapy.