Abstract

AimsSinonasal inverted papillomas (SIP) and sinonasal squamous cell carcinomas (SNSCC) are sinonasal tumors with unclear etiology and pathogenesis. Epstein-Barr virus (EBV) has been detected in these tumors but information concerning their association is still limited. This study aimed to investigate the prevalence in, and association of EBV infection with SIP and SNSCC in northeastern Thailand.MethodsDNA was extracted from 226 formalin-fixed, paraffin-embedded tissues including 80 nasal polyps (NP; the control group), 64 SIP and 82 SNSCC samples. Presence of EBV in these tissues was investigated using real-time PCR and their localization within tissues was confirmed using in situ hybridization (ISH). Characteristics of patients and the association of EBV prevalence with sinonasal tumors were analyzed.ResultsSIP and SNSCC were frequently found in people aged > 50 years and more often in males than in females (3:1 ratio). EBV infection was detected in 33.75, 64.06 and 37.80% of NP, SIP and SNSCC tissues, respectively, by real-time PCR. There was a statistically significant association between EBV infection and SIP (odds ratio [OR] = 3.52). This was not the case for SNSCC when compared to the NP group (OR = 1.83). Interestingly, EBV infection tended to be associated with inflammation and dysplasia in SIP. In SNSCC, EBV was mostly found in samples with undifferentiated or poorly differentiated cell types as well as in recurrent cases and lymph-node metastasis. Using ISH, EBV was detected only in infiltrating lymphocytes within the tumor stroma, not in the tumor epithelial cells.ConclusionsInfiltrating lymphocytes containing EBV in the tumor microenvironment might enhance tumorigenesis of SIP and SNSCC. The mechanism by which EBV promotes development of SIP and SNSCC needs to be elucidated in the future.

Highlights

  • Epstein-Barr virus (EBV) is a human herpesvirus 4 present in more than 90% of the world’s population

  • Tissue samples and patient characteristics Tissue samples of nasal polyps (NP), sinonasal inverted papillomas (SIP) and sinonasal squamous cell carcinomas (SNSCC) from 2010 to 2016 were retrieved from archival paraffin blocks stored in the Department of Pathology, Faculty of Medicine, Khon Kaen University

  • Statistical analysis using multiple logistic regression shown that age was the only factor significantly associated with Sinonasal inverted papilloma (SIP) and SNSCC

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Summary

Introduction

Epstein-Barr virus (EBV) is a human herpesvirus 4 present in more than 90% of the world’s population. Sinonasal inverted papilloma (SIP) is a benign tumor of the nasal cavity and paranasal sinuses [7, 8]. It is seen three times more frequently in males than in females at the fifth and sixth decade of life [9]. The term “inverted papilloma” describes the epithelial growth inward into the underlying supportive tissue of the nasal cavity and paranasal sinuses that is characteristic of the tumor [10]. It is the second most common benign tumor of the sinonasal tract, representing approximately 0.5–4% of all primary nasal tumors. An association between EBV infection and SIP has been reported in a few studies [13]

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