Abstract
Simple SummaryEpstein–Barr virus DNA positivity, age ≥ 55 years, cigarette smoking, and high BCL-2, B2M, and CD161 expression were identified as independent risk factors for primary laryngeal squamous cell carcinoma. A high EBER signal and low CD3 expression significantly and independently predicted local recurrence and disease-free survival within five years. The information obtained in this study improves our understanding of viral infections in laryngeal cancer, and may guide future prevention, treatment, and follow-up strategies. Mounting molecular evidence supports Epstein–Barr virus (EBV) involvement in the pathogenesis of laryngeal squamous cell carcinoma (LSCC); however, the epidemiological data are inconsistent. In this retrospective case-control study, we aimed to determine whether EBV infection underlies the risk and prognosis of LSCC. The prevalence of EBV infection, as analyzed using an EBV DNA polymerase chain reaction assay, was significantly higher in 42 Taiwanese patients with newly diagnosed primary LSCC, compared to 39 age- and sex-matched control patients without cancer (48% vs. 19%). Furthermore, most of the EBER signals detected using in situ hybridization were localized to the nuclei of tumor-infiltrating lymphocytes. In multivariate analysis, EBV DNA positivity, age ≥ 55 years, cigarette smoking, and high BCL-2, B2M, and CD161 expression (assessed using immunohistochemistry) were identified as independent risk factors for LSCC. Furthermore, five-year local recurrence and disease-free survival rates were 34% and 58%, respectively, with a high EBER signal and low CD3 expression independently predicting five-year local recurrence and disease-free survival. Our comprehensive profiling data accurately identified patients at risk for LSCC development, local recurrence, or disease-free survival. The information obtained in this study improves our understanding of EBV infection in LSCC, and may guide precision medicine for patients with LSCC.
Highlights
The long-term survival of patients with laryngeal squamous cell carcinoma (LSCC) is excellent when locoregional recurrence is controlled [1]
This study aimed to investigate the effects of Epstein–Barr virus (EBV) infection on long-term prognoses, including five-year local recurrence (LR), neck recurrence (NR), distant metastasis (DM), disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS), of primary LSCCs
BCL-2 overexpression might not contribute to the prognostic significance of LSCC development [43], we found that both EBV DNA positivity and BCL-2 overexpression in the larynx were independently associated with a risk of LSCC
Summary
The long-term survival of patients with laryngeal squamous cell carcinoma (LSCC) is excellent when locoregional recurrence is controlled [1]. The etiologic risk factors for primary and recurrent LSCC need to be thoroughly studied; potential risk factors include cigarette smoking, alcohol consumption, environmental carcinogens, and gene mutations [4]. The effects of EBV infection on the host’s genetic susceptibility (e.g., expression of BCL-2 (the Akt signaling pathway) [16], MYC (the TGF-β signaling pathway) [17], and p16INK4a (the cell cycle G1/S checkpoint signaling pathway) [7]) and immune response (e.g., expression of B2M [18], CD3 [19], and CD161 [20]) to LSCC have not been reported in detail. The relationship between viral infections and LSCC development and prognosis requires further investigation
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