Nasopharyngeal Cancer Screening Results May “Predict” Development of Related Cancer and Improve Early Diagnosis, CUHK Study Finds

A recent study conducted by The Chinese University of Hong Kong (CUHK)’s Faculty of Medicine (CU Medicine) has shown that individuals with detectable plasma Epstein–Barr virus (EBV) DNA but without an immediately identifiable nasopharyngeal cancer (NPC) after further investigation with nasal endoscopic examination and magnetic resonance imaging (MRI), have a higher risk of developing NPC in 3 to 5 years, up to 17 times higher than those tested “negative” in the test. The non-invasive liquid biopsy techniques not only could be used for early cancer detection but may also indicate the risk for future cancer development.

The important findings were published in NEJM Evidence, a journal from The New England Journal of Medicine, in June 2023.

Detecting Cancer-associated Aberrations through Liquid Biopsy Can Tell the Future Cancer Risk

The research team conducted a "Plasma DNA Screening" on over 20,000 middle-aged Chinese males in Hong Kong without NPC symptoms between 2013 and 2016. Among them, 309 persons had persistently positive results on initial and follow-up tests, and 34 people were confirmed as having NPC in the first-round screening, of which as many as 70% were early-stage patients (in general, 80% of unscreened patients were diagnosed with NPC at late stages, where the cancer has already spread and deteriorated). The study has fully demonstrated that screening can effectively shift the detection to significantly earlier stages, improving mortality and reducing the side effects of treatments. The landmark results of this study were published in The New England Journal of Medicine, a top international medical journal, in 2017.

To understand the long-term significance of “false-positive” results in individuals and the clinical implications, the research team conducted a second-round screening for the same group of participants 3 to 5 years after the first-round screening.

Detectable Plasma EBV DNA Indicates a Risk of Developing NPC In the Next 3-5 Years by Up to About 17 Times

The team found a strong positive correlation between plasma EBV DNA results of the two rounds of screening. Compared with individuals with undetectable first-round EBV DNA (i.e., relative risk, 1), the relative risks of developing NPC identified in the second round were 4.4 and 16.8, respectively, for individuals with transiently positive and persistently positive EBV DNA results.

The study also suggests that the invasion of EBV into epithelial cells is a critical step in its carcinogenesis, and plasma EBV DNA positivity probably reflects the presence of such a process. The research team speculated that the existence of such cancer-related mutations in plasma may precede and portend the development of cancer, which serves as a warning sign for future cancer!

Professor Dennis LO, Director of the Li Ka Shing Institute of Health Sciences at CUHK, who led the study, said: "Although some test results of participants were positive, cancer was not identified upon further investigation. Our large-scale prospective study proves that detection of cancer-associated changes in plasma through liquid biopsy could be able to reflect the risk for future cancer development."

The Results Indicate Clinical Significance. Specialists Recommend Hong Kong Citizens Undergo Annual Screening

NPC is a common type of cancer in southern China, including Hong Kong, and Southeast Asia, and is one of the most aggressive head and neck cancers – the cancer frequently metastasizes to distant lymph nodes and organs. According to the latest data from the Hong Kong Cancer Registry, there are nearly 800 new NPC cases in Hong Kong every year, while it is also the top cancer among young men aged between 20-44.

NPC is closely associated with EBV infection. The study’s results reflect that NPC screening with circulating EBV DNA analysis can be used to detect early-stage NPC, and reflect the risk of future cancer development, thereby one can make more appropriate follow-up arrangements. Ear, Nose, and Throat Specialists also recommend that Hong Kong citizens should consider undergoing relevant screening every 1-2 years, and if there is a family history of NPC, other high-risk factors, or suspected symptoms, more frequent examinations are necessary.

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