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Screening improves nasopharyngeal carcinoma detection, survival
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Screening for circulating cell-free Epstein-Barr virus DNA detected nasopharyngeal carcinoma at earlier stages and improved outcomes, according to a study published The New England Journal of Medicine.
“Most analysis of DNA released from tumor cells focuses on the guidance of treatment choice and to detect disease recurrence after treatment,” K.C. Allen Chan, FRCPA, professor of chemical pathology at Chinese University of Hong Kong, told HemOnc Today. “There is little information on the potential application of plasma DNA analysis for the screening of early cancer.
“In this study, we have demonstrated that plasma DNA analysis is useful for the screening of early asymptomatic cancers, and the detection of early cancer can improve PFS,” Chan added.
Nasopharyngeal carcinoma is especially prevalent in Southeast Asia, where incidence among middle-aged men in endemic areas is up to 35 cases per 100,000 persons. Smoking, consumption of salted fish and family history are among the risk factors for early nasopharyngeal carcinoma, which is relatively asymptomatic.
Five-year survival of patients with stage I disease is 95%; however, survival at stage IV is just over 60%. About 80% of patients present with locally advanced disease or distant metastasis at diagnosis.
Circulating cancer-derived Epstein-Barr Virus (EBV) DNA — detected using real-time polymerase chain reaction in liquid biopsies — has been established as a tumor biomarker for nasopharyngeal carcinoma, with a sensitivity of 96% and a specificity of 93%.
Researchers analyzed EBV DNA in plasma specimens from 20,174 men aged 40 to 62 years (median age, 52 years) with no symptoms of nasopharyngeal carcinoma.
Median follow-up was 22 months.
Of the 1,112 men (5.5%; median age, 53 years) who tested positive for EBV DNA at baseline, 43% currently or formerly smoked and 90.8% did not have a first-degree relative with a history of nasopharyngeal carcinoma.
Men who initially tested positive for EBV DNA underwent retesting about 4 weeks later (median interval, 34 days).
Among 309 men (1.5% of all patients; 27.8% of those positive at baseline) with persistently positive results, 300 underwent nasal endoscopic examination, and 275 underwent both nasal endoscopic examination and MRI. Nine men declined further testing.
Subsequent diagnosis of nasopharyngeal carcinoma occurred in 34 (11%) of these participants.
Researchers compared data on stage of diagnosis from these men with data from 1,278 men aged 40 to 62 years derived from a historical cohort of all patients who received treatment at public oncology centers in Hong Kong over 5 years.
A significantly higher proportion of participants with screen-detected nasopharyngeal carcinoma had stage I or stage II disease compared with the historical cohort (71% vs. 20%; P < .001).
A greater proportion of men with screen-detected disease also achieved 3-year PFS (97% vs. 70%; HR = 0.1; 95% CI, 0.05-0.18).
Nasopharyngeal carcinoma developed in one man with negative EBV DNA within 1 year of testing. Based on that occurrence, screening had a sensitivity of 97.1% and a specificity of 98.6%.
One patient who declined additional testing with nasal endoscopy and MRI presented with advanced nasopharyngeal carcinoma 32 months after enrollment and subsequently died 2 months later.
“The efficacy of the study is a surprising finding as 70% of the patients identified by screening had stage I and II disease,” Chan said. “In comparison, 75% of nasopharyngeal carcinoma patients presented with stage III and IV disease historically. As the treatment for early nasopharyngeal carcinoma is very effective, the shifting of the stage has resulted in a very significant improvement in PFS.”
In the United States, EBV DNA analysis costs $30, endoscopic exam costs $80 and MRI costs $1,000. Based on the study results, 593 participants would need to be screened at a cost of $28,600 to detect one case of nasopharyngeal carcinoma.
“Overall, this study has provided important data that screening of asymptomatic cancers through plasma DNA analysis is feasible,” Chan said. “As nasopharyngeal carcinoma is one of the most common cancers in Southern China and Southeast Asia, it may be worthwhile to consider implementing screening in these endemic areas.”
Because early-stage nasopharyngeal carcinoma is usually cured with radiation therapy, and because almost half the men in the study with nasopharyngeal carcinoma had stage I disease, the findings are clinically important and suggest lives have been saved because of this screening, Richard F. Ambinder, MD, PhD, director of hematologic malignancies at Johns Hopkins University School of Medicine, wrote in an accompanying editorial.
However, Ambinder cautioned that a retrospective survey conducted at Sidney Kimmel Comprehensive Cancer Center showed only 1% of patients with EBV DNA detected in blood samples had nasopharyngeal carcinoma.
“Thus, the positive predictive value of EBV DNA in plasma to screen for nasopharyngeal carcinoma is much lower outside of endemic areas, high-risk populations, or high-risk persons than it is in [Southern China and Southeast Asia],” Ambinder wrote. “However, the study by Chan [and colleagues] shows that in the right context, population screening of plasma DNA is a very promising approach to detect early-stage cancer.” – by Chuck Gormley
For more information:
K.C. Allen Chan, FRCPA, can be reached at Department of Chemical Pathology, Chinese University of Hong Kong, Prince of Wales Hospital, 30-32 Ngan Shing St., Shatin, Hong Kong; email: allen@cuhk.edu.hk.
Disclosures: The Kadoorie Charitable Foundation and research grants from the Hong Kong government funded this study. Chan reports he serves as director, holds equity in, receives grant support from, and receives royalties for patents from Cirina; holds equity in Grail; receives royalties for patents from Sequenom; and receives royalties for patents and consulting fees from Xcelom. Please see the full study for a list of all other researchers’ financial disclosures. Ambinder reports no relevant financial disclosures.
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