EBV-DNA Screening for Early Detection of Nasopharyngeal Cancer
ABSTRACT & COMMENTARY
Financial Disclosure: Clinical Oncology Alert’s Editor, William Ershler, MD; nurse planner, Irene Q. Flores, RN, BSN OCN; peer reviewer, V.R. Veerapalli, MD; executive editor, Leslie Coplin; and managing editor, Neill Kimball report no financial relationships relevant to this field of study
Synopsis: In a study conducted in Hong Kong, plasma Epstein-Barr virus (EBV) DNA levels were examined in 1308 adults who were not known to have nasopharyngeal cancer (NPC). Of these, 69 patients had detectable EBV DNA and three were found to have early NPC. The level of EBV DNA remained elevated on serial evaluations in the three patients but was only transiently elevated in the majority of those who remained free of NPC. In selected high-risk populations, plasma EBV DNA analysis may prove to be a useful screening measure for NPC.
Source: Chan KCA, et al. Early detection of nasopharyngeal carcinoma by plasma Epstein-Barr virus DNA analysis in a surveillance program. Cancer 2013;119:1838-1844.
Nasopharyngeal carcinoma (NPC) is a relatively uncommon cancer in western cultures but remains highly prevalent in Southeast Asia.1 Although the rates of occurrence are less than in China, the prevalence of NPC remains high in Chinese Americans.2 Success of treatment also remains very much stage-dependent, with 5-year survival rates of approximately 90% for patients who present with localized disease but less than 50% for those with regional lymph nodes and much less than that for those with distant metastases. Unfortunately, most patients present with either regional or distant disease.3 Strategies to enhance early detection are of critical importance.
Over the past decade, an awareness of the importance of detectable, tumor-associated nucleic acids in the plasma of patients with certain malignancies has developed, and it has been speculated that such may be useful as tumor markers, particularly in defining response to therapy and detecting early recurrence.4 In this context, plasma Epstein Barr virus (EBV) DNA has proven useful in the management of NPC.5 The current research was aimed at determining whether the detection of EBV DNA would prove useful as a screening tool for NPC.
In a study conducted over a 6-month period in community clinics associated with Prince of Wales Hospital in Hong Kong, 1318 volunteers aged 40-60 years were prospectively recruited. None of the subjects were known to have NPC or any active malignancy. Plasma EBV DNA analysis and immunoglobulin A (IgA) serology for the EBV viral capsid antigen (VCA) were performed for each participant. Every individual who had a positive test result (either EBV DNA or IgA VCA) underwent an endoscopic examination of the nasopharynx and follow-up plasma EBV DNA analysis after 2-4 weeks. For participants who had positive plasma EBV DNA results, the plasma EBV DNA test was repeated at 6 months and 18 months after the initial screening. All participants were followed for 2 years to record the development of NPC.
Of the 1318 subjects, 69 (5.2%) had detectable levels of EBV DNA at the time of enrollment and three were found to have NPC. These three patients remained positive for EBV DNA during follow-up analysis. Only one of those patients was positive for EBV serology. In one patient who had NPC with a small tumor confined to the mucosa, the tumor was not detectable on endoscopic examination. Because of a two-fold increase in plasma EBV DNA on the follow-up analysis, that patient underwent magnetic resonance imaging, which revealed the tumor. Among the participants who did not have NPC but who initially had positive plasma EBV DNA results, approximately 66% had negative EBV DNA results after a median of 2 weeks.
Among the 63 individuals who completed the test on the three occasions, 11 (17%) were positive in all three analyses. Each individual who had a positive plasma EBV DNA result on the follow-up visits at 6 months or 18 months underwent a follow-up nasal endoscopic examination. All of these individuals were negative for NPC. All participants in the study were interviewed 2 years after enrollment. Apart from the three patients who had NPC identified at enrollment, none of the participants had developed NPC.
In this relatively small study, plasma EBV DNA analysis proved useful for detecting early NPC in individuals without a clinical suspicion of NPC. There were three detected cases, and careful follow-up of the full cohort revealed no other cases of NPC in the subsequent 2 years. Repeating the test in those who initially had positive results differentiated those with NPC from those who had false-positive results.
The study emphasizes the potential importance of examining tumor-associated nucleic acids as a novel screening strategy. However, considerable additional study will be required before the expense of such an approach can be justified on a large scale. Nonetheless, for patients at risk (particularly Chinese or Chinese Americans), such studies are clearly warranted. In the meantime, medical oncologists should be aware of the important utility of plasma EBV DNA assessment in the management of selected patients with NPC.
1. Wei WI, Sham JS. Nasopharyngeal carcinoma. Lancet 2005;365:2041-2054.
2. Sun LM, et al. Trends in the incidence rates of nasopharyngeal carcinoma among Chinese Americans living in Los Angeles County and the San Francisco metropolitan area, 1992-2002. Am J Epidemiol 2005;162:1174-1178.
3. Lee AW, et al. Treatment results for nasopharyngeal carcinoma in the modern era: The Hong Kong experience. Int J Radiat Oncol Biol Phys 2005;61:1107-1116.
4. Schwarzenbach H, et al. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 2011;11:426-437.
5. Leung SF, et al. Plasma Epstein-Barr viral deoxyribonucleic acid quantitation complements tumor-node-metastasis staging prognostication in nasopharyngeal carcinoma. J Clin Oncol 2006;24:5414-5418.