Abstract

Nasopharyngeal carcinoma (NPC) is consistently associated with Epstein-Barr virus (EBV) and highly prevalent in Indonesia. EBV-DNA load can be used for early diagnosis and may have prognostic value. In this study, EBV-DNA load was evaluated in minimal invasive nasopharyngeal (NP) brushings and whole blood for initial diagnosis and therapy assessment against the standard-of-care diagnosis by biopsy with EBV-RISH and standard EBV-IgA serology. NP brushings and blood samples were collected from 289 consecutive ENT patients suspected of NPCs and 53 local healthy controls. EBV-DNA load was quantified by real-time PCR and serology by peptide-based EBV-IgA ELISA. Tissue biopsies were examined by routine histochemistry and by EBER RNA in situ hybridization. Repeated NP brushing was well tolerated by patients and revealed high viral load in the 228 NPC cases at diagnosis than 61 non-NPC cancer cases and healthy controls (P < 0.001). The diagnostic value of EBV-DNA load in blood and EBV-IgA serology was inferior to the NP brush results. The level of EBV-DNA load in brushes of patients with NPC was not related to T, N, or M stage, whereas elevated EBV-DNA load in blood correlated with N and M stage. EBV-DNA levels in brushings and whole blood showed a significant reduction at 2 months after treatment (P = 0.001 and P = 0.005, respectively), which was not reflected in EBV-IgA serology. NP brush sampling combined with EBV-DNA load analysis is a minimal invasive and well-tolerated diagnostic procedure, suited for initial diagnosis and follow-up monitoring of NPCs.

Highlights

  • Nasopharyngeal carcinoma (NPC) is a distinct head and neck cancer, occurring at high frequency in Southeast-Asian, North-African, and Inuit populations [1]

  • The level of Epstein-Barr virus (EBV)-DNA load in brushes of patients with NPC was not related to T, N, or M stage, whereas elevated EBV-DNA load in blood correlated with N and M stage

  • EBV-DNA levels in brushings and whole blood showed a significant reduction at 2 months after treatment (P 1⁄4 0.001 and P 1⁄4 0.005, respectively), which was not reflected in EBV-IgA serology

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Summary

Introduction

Nasopharyngeal carcinoma (NPC) is a distinct head and neck cancer, occurring at high frequency in Southeast-Asian, North-African, and Inuit populations [1]. In Indonesia, with an ethnically diverse population of 225 million people, NPC is the most common head and neck cancer with high prevalence among native populations and an overall. In the Dr Cipto Mangunkusumo Hospital (Jakarta, Indonesia), NPC is the fifth most frequent cancer overall after cervical carcinoma, breast cancer, colon, and skin cancer with an incidence of 6.6% (cervical cancer 16.1%, breast cancer 14.5%, colorectal cancer 9.9%). More than 85% of patients with NPCs in Indonesia present in the clinic with advanced stage of disease and treatment outcome is poor [3]

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