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Prognostic role of human papilloma virus status in hypopharyngeal squamous cell carcinoma.

ABSTRACT: Objective:Although the prognostic role of human papilloma virus (HPV) status in oropharyngeal head and neck squamous cell carcinoma (SCC) is well established, growing evidence shows that there may be a prognostic role for HPV status in hypopharyngeal SCC. The objective of this study was to determine the prognostic role of HPV status in hypopharyngeal SCC. Methods:We performed a retrospective, population-based analysis of 1934 adult patients with HNSCC diagnosed between 2010-2016 and treated with a combination of surgery and/or radiotherapy, with or without chemotherapy, and a subset of 641 patients with hypopharyngeal SCC and known HPV status included in the Surveillance, Epidemiology, and End Results (SEER) Head and Neck with HPV Status Database. Patient data were used to determine the adjusted 2-year cancer-specific survival (CSS) and overall survival (OS) for the entire cohort and the specific subgroup of hypopharyngeal cancer patients with known HPV status. Results:Of the 1934 hypopharynx SCC cases, HPV status was unknown in 1294 (66.9%), and 167 (8.6%) were HPV positive; among hypopharynx cases with known HPV status, 21.6% were HPV positive. In models adjusting for sex, age, race/ethnicity, marital status and stage, patients with HPV-positive hypopharyngeal tumors had improved CSS compared with patients with HPV-negative tumors (CSS: HR: .57, 95% CI = .38 to .86, P =?.008; OS: HR: .49, 95% CI = .34 to .71, P =?<.001). Conclusion:Our findings in a large cohort of hypopharyngeal SCC with known HPV status and cancer-specific survival support the hypothesis that HPV has a prognostic role in hypopharyngeal cancer. Consideration should be given to increased testing for HPV in hypopharyngeal SCC. Level of Evidence:4.

SUBMITTER: Marshall DC

PROVIDER: S-EPMC7585257 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Prognostic role of human papilloma virus status in hypopharyngeal squamous cell carcinoma.

Marshall Deborah C DC Kao Derek D DD Bakst Richard R Sharma Sonam S Ferrandino Rocco R Rosenzweig Kenneth K Wisnivesky Juan J Sigel Keith K

Laryngoscope investigative otolaryngology 20200811 5

<h4>Objective</h4>Although the prognostic role of human papilloma virus (HPV) status in oropharyngeal head and neck squamous cell carcinoma (SCC) is well established, growing evidence shows that there may be a prognostic role for HPV status in hypopharyngeal SCC. The objective of this study was to determine the prognostic role of HPV status in hypopharyngeal SCC.<h4>Methods</h4>We performed a retrospective, population-based analysis of 1934 adult patients with HNSCC diagnosed between 2010-2016 a ...[more]

PMID: 33134533

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Project description:Purpose:The expression of programmed death-ligand 1 (PD-L1) is common in various solid human cancers and it is an important therapeutic target. However, the expression pattern, clinical significance and potential mechanism of PD-L1 in hypopharyngeal squamous cell carcinoma (HSCC) are still lacking. Methods:PD-L1 expression in HSCC tumor tissues and paired adjacent hypopharyngeal mucosal tissues was detected using immunohistochemistry assay, and the clinical significance of PD-L1 in HSCC was characterized. In vitro assays including cell viability assays, migration assays, invasion assays as well as Western blot assays were performed to illuminate the biological functions and underlying molecular mechanisms of PD-L1 in HSCC development. Results:PD-L1 expression was detected in HSCC samples but we found no positive expression in matched normal hypopharyngeal mucosal tissues. The levels of PD-L1 expression were significantly correlated with advanced clinical progression and poor patient survival. Multivariable analysis of Cox model showed that PD-L1 expression was an independent predictor for the prognosis of HSCC patients. Functional experiments showed that the ectopic expression of PD-L1 markedly influenced the proliferation, migration and invasion of FaDu cells in vitro. Mechanistically, investigations demonstrated that PD-L1 could promote the epithelial-mesenchymal transition of FaDu cells. Meanwhile, PD-L1 knockdown inhibited, while PD-L1 overexpression activated the Akt-mTOR signaling pathway in FaDu cells. The EMT induced by PD-L1 overexpression could be reversed by the Akt inhibitor. Conclusion:In summary, the expression of PD-L1 can act as a significant biomarker for the adverse clinicopathological features and poor prognosis of patients with HSCC. PD-L1 can promote the proliferation, migration and invasion of FaDu cells and consequently enhance the aggressiveness. Moreover, PD-L1 induces EMT through AKT-mTOR signaling pathway. These suggest that PD-L1 has important tumor-intrinsic functions independent of its immunopathogenic effects.

Dataset Information

Prognostic role of human papilloma virus status in hypopharyngeal squamous cell carcinoma.

Publications

Prognostic role of human papilloma virus status in hypopharyngeal squamous cell carcinoma.

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