Early Detection of Nasopharyngeal Cancer With EBV DNA

Roxanne Nelson, BSN, RN

August 09, 2017

Individuals who are at high risk for nasopharyngeal carcinoma may benefit from screening using circulating cell–free Epstein-Barr virus (EBV) DNA, suggest researchers from China. This cancer has a high prevalence in Southeast Asia, they note, especially among middle-aged men.  

The team, led by Y.M. Dennis Lo, FRS, from Chinese University of Hong Kong, China, showed that such screening detected the cancer at an earlier stage, leading to superior outcomes.

The results are published August 10 in the New England Journal of Medicine In an accompanying editorial, Richard F. Ambinder, MD, PhD, from the Johns Hopkins School of Medicine, Baltimore, Maryland, says this is a "very promising approach" in the right setting.

Screening Asymptomatic Men

The researchers note that the pathogenesis of nasopharyngeal cancer  is closely associated with EBV and that circulating EBV DNA in plasma has already been established as a tumor marker, with a sensitivity of 96% and a specificity of 93%.

The current  prospective study evaluated the use of EBV DNA in plasma samples for screening in asymptomatic persons. The cohort comprised  20,174 men aged 40 to 62 years.

EBV DNA was detected in plasma samples obtained from 1112 participants (5.5%).

A total of 309 participants had persistently positive results on a repeated sample, and 300 underwent further examination with endoscopic examination and/or MRI. Nasopharyngeal carcinoma was ultimately diagnosed in 34 (11%) of this subset.

The screened patients had a significantly higher proportion of stage I or II disease compared with historical controls (71% vs. 20%; P < .001). Almost half of the group (n = 16 [47%]) had stage I disease, a rate substantially higher than the 5% to 7% of patients diagnosed with stage I disease that has generally been reported in the literature, the team notes.

In addition, patients diagnosed after screening also achieved better 3-year progression-free survival compared with the control group (97% vs 70%; P < .001).

Promising in the Right Context

In his editorial,  Dr Ambinder points out that early-stage nasopharyngeal carcinoma is generally curable with local radiation therapy. Because almost half the participants with nasopharyngeal carcinoma in this study had stage I disease, the "findings are clinically important and the data presented suggest that lives have been saved because of this screening," he comments.

Dr. Ambinder points out that measuring viral loads has been useful for several infectious diseases, but as measurements of EBV DNA in plasma become more widely used, "it will be important that measurement of the EBV DNA viral copy number not be misinterpreted as a measurement of virions."

"The target of measurement in plasma samples obtained from patients with nasopharyngeal carcinoma is predominantly viral sequences released from tumor cells into cell-free blood — a very important distinction," he writes.

Dr Ambinder also cautions that outside of endemic areas and high-risk patients and populations, the positive predictive value of plasma EBV DNA for screening is much lower. For example, a retrospective survey conducted at Johns Hopkins showed that among unselected patients who had EBV DNA detected in plasma samples, only about 1% had nasopharyngeal carcinoma.

But in the right context, as demonstrated in the current study, "population screening of plasma DNA is a very promising approach to detect early-stage cancer," Dr Ambinder writes.

"Like cervical cytologic testing or testing for human papillomavirus in the cervix for early detection of cervical cancer, plasma EBV DNA screening may profoundly change the natural history of nasopharyngeal carcinoma," he suggests.

The study was funded by the Kadoorie Charitable Foundation and a grant from the Research Grants Council of the Hong Kong government under the Theme-based Research Scheme. Several coauthors report relationships with industry, as noted in the paper. Dr Ambinder has disclosed no relevant financial relationships.

N Engl J Med. 2017;377:513-522, 584-585. Abstract, Editorial

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