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The Chinese University of Hong Kong (CUHK)’s Faculty of Medicine (CU Medicine) research team has identified molecular features in Epstein-Barr virus (EBV) DNA specifically associated with nasopharyngeal cancer (NPC) by using next-generation sequencing technology, enabling more accurate risk stratification. The study has also found that individuals with cancer-associated EBV DNA detected in blood face an 87-fold increase in risk of developing NPC in the future, compared to plasma EBV DNA-negative individuals. The findings have been published in the international medical journal Cancer Cell.

Earlier studies by CU Medicine have shown that plasma EBV DNA screening can detect early-stage NPC in asymptomatic individuals and predict future cancer risk. In high-incidence regions such as Hong Kong and other parts of Southern China, nearly all NPC cases are associated with EBV infection, making the detection of tumour-derived EBV DNA in plasma a robust diagnostic tool. However, as EBV infection is very common (over 90% of the population has been infected at some point), testing via conventional  polymerase chain reaction (PCR) would reveal detectable plasma EBV DNA in non-cancer individuals, creating challenges for its use in screening for NPC.

In the latest study, by using next-generation sequencing technology, the research team has identified molecular features in EBV DNA specifically associated with NPC, which differ significantly from the EBV DNA found in individuals with general EBV infections. Compared with PCR testing alone, it can more accurately identify people at high risk of NPC. The team has also found that individuals with cancer-associated EBV DNA detected in their blood were shown to have an increased risk of 87 folds for developing NPC in the next four years compared to plasma EBV DNA-negative individuals. This screening strategy enables more accurate risk stratification, allowing more intense cancer surveillance among the high-risk subgroup.

CUHK has established plasma EBV DNA for screening for NPC and predicting future cancer risk through a study spanning over a decade

NPC is one of the most aggressive head and neck cancers, and frequently spreads to distant lymph nodes and organs. According to 2022 data from the Hong Kong Cancer Registry, over 700 new cases of NPC are diagnosed annually in Hong Kong, ranking it among the top 10 most common cancers in males in the region.

Between 2013 and 2016, CUHK’s research team conducted plasma EBV DNA screening on over 20,000 asymptomatic middle-aged males in Hong Kong, and successfully identified 34 patients with NPC, of whom 70% were diagnosed at stage I or II. This has demonstrated for the first time that analysing plasma EBV DNA enables early NPC detection before the onset of symptoms. In a follow-up study carried out between 2017 and 2020, three to five years after the initial screening, the team performed a second-round of NPC screening among the same subjects and identified 24 additional NPC cases. This study further revealed that subjects with plasma EBV DNA detectable by PCR have an increased risk of NPC four years later.  

Characterisation of plasma EBV DNA by sequencing differentiates EBV DNA originating from cancer cells and that from general EBV infections, enhancing accuracy of future NPC risk prediction 

Dr Jacky Lam Wai-kei, Assistant Professor in the Department of Chemical Pathology at CU Medicine and Assistant Scientific Director of the Centre for Novostics, said: “Our previous research data showed that some non-cancer individuals were also tested positive for plasma EBV DNA via PCR in the first round of screening due to viral reactivation. To accurately identify high-risk groups, we conducted in-depth analysis of the positive cases from the first round of screening, using next-generation sequencing technology to profile plasma EBV DNA characteristics. This approach successfully differentiated cancer-associated viral DNA and infection-related viral DNA. These molecular features included size, end motifs, and methylation, analysed using the FRAGMA technology previously established by our team. The research results revealed a distinct plasma DNA profile associated with NPC – individuals with these features were at an 87-fold increased risk of developing cancer in the second round compared to EBV DNA-negative individuals. The innovative finding not only confirms the clinical value of plasma EBV DNA testing but also establishes a novel molecular biomarker system for precision NPC screening.”

Professor Allen Chan Kwan-chee, Chairman and Professor in the Department of Chemical Pathology at CU Medicine and Co-Director of the Centre for Novostics, added: “Plasma DNA-based tests are increasingly adopted for the screening of various types of cancer. Our latest research confirmed that integrating DNA fragmentomics analysis with existing blood tests for cancer can further enhance the accuracy of cancer prediction. This approach not only facilitates early detection to initiate timely treatment but also optimises risk management for high-risk groups through refined screening protocols. 

The members of the team who worked on this research come from CUHK’s Li Ka Shing Institute of Health Sciences and State Key Laboratory of Translational Oncology, CU Medicine’s Department of Chemical Pathology, Department of Otorhinolaryngology, Head and Neck Surgery, Department of Imaging and Interventional Radiology and Department of Clinical Oncology, and the Centre for Novostics at Hong Kong Science Park. The Centre for Novostics is supported by the Hong Kong SAR government’s InnoHK scheme.