Ferrari et al. BMC Cancer 2012, 12:208 http://www.biomedcentral.com/1471-2407/12/208 unusually long OS (median 28 months), which have never reported elsewhere [45,46], suggest there may have been a selection bias. Furthermore, the need to analyse multiple plasma samples limits the usefulness of this method in clin- ical practice. In a larger cohort of patients receiving chemotherapy for metastatic disease, monitoring EBV DNA levels proved to be useful in predicting which patients would survive longer (i.e. those with low pre-treatment and un- detectable post-treatment levels) [47], which is in line with our experience as some of our long-term survivors maintained low EBV DNA copy numbers years after the end of chemotherapy (data not shown). Conclusions In an era of new biomolecular marker development, the measurement of plasma EBV DNA levels is as essential in the West as it is in the East. Given its high degree of accuracy, all NPC patients with loco-regionally advanced disease should be regularly monitored in order to detect any increase in plasma levels and diagnose recurrence as early as possible. Competing interests The authors declare that they have no competing interests. Authors’ contributions DF and PF conceived the study and participated in its design and coordination. CC, CB, FB and FC participated in designing the study. AL and IF performed the statistical analysis. AM, FC and DA participated in coordinating the study. All of the authors read and approved the final manuscript. Acknowledgements We thank Barbara Cassani for her contribution to the writing of the Methods Section. Author details 1Division of Medical Oncology and Department of Medicine, Surgery and Dentistry, San Paolo Hospital and University of Milan, Via Di Rudinì 8, Milan, Italy. 2Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, Milan, Italy. 3Head and Neck Surgery, European Institute of Oncology, Via Ripamonti, Milan, Italy. 4Division of Radiotherapy, European Institute of Oncology, Via Ripamonti, Milan, Italy. Received: 12 November 2011 Accepted: 16 May 2012 Published: 30 May 2012 References 1. Parkin DM, Whelan SL, Ferlay J, Raymond L, Young J: Cancer Incidence in Five Continents. VIIth edition. Lyon: International Agency for Research on Cancer; 1997:814–815. IARC Scientific Publications No.143. 2. Parkin D: Cancer Burden in the year 2000. The global Picture. Eur J Cancer 2001, 37:S4–S66. 3. Nielsen NH, Mikkelsen F, Hansen JP: Nasopharyngeal cancer in Greenland. The incidence in an Arctic Eskimo population. Acta Pathol Microbiol Scand 1977, 85:850–858. 4. Yu MC, Yuan JM: Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol 2002, 12:421–429. 5. Huang TB, Min HQ, Min HQ, Wang HM, Zhang EP, Hong MH: Nasopharyngeal Carcinoma Research. Guangzhou: Guangdong Science and Technology Press; 1998:6–12. Page 6 of 7 6. Devi BCR, Pisani P, Tang TS, et al: High incidence of nasopharyngeal carcinoma in native people of Sarawak, Borneo Island. Cancer Epidemiol Biomarkers Prev 2004, 13:482–486. 7. Adham M, Kurniawan AN, Muhtadi AI, et al: Nasopharyngeal carcinoma in Indonesia: epidemiology, incidence, signs, and symptoms at presentation. Chin J Cancer 2012. doi: 10.5732/cjc.011.10328. Epub ahead of print. 8. Micheli A, Francisci S, Krogh V, Rossi AG, Crosignani P: Cancer prevalence in Italian cancer registry areas: the ITAPREVAL study. ITAPREVAL Working Group. Tumori 1999, 85:309–369. 9. Heng DM, Wee J, Fong KW, Lian LG, Sethi VK, Chua ET, Yang TL, Khoo Tan HS, Lee KS, Lee KM, Tan T, Chua EJ: Prognostic factors in 677 patients in Singapore with non disseminated nasopharyngeal carcinoma. Cancer 1999, 86:1912–1920. 10. Sanguineti G, Geara FB, Garden AS, Tucker SL, Ang KK, Morrison WH, Peters LJ: Carcinoma of the nasopharynx treated by radiotherapy alone: determinants of local and regional control. Int J Radiat Oncol Biol Phys 1997, 37:985–996. 11. Qin DX, Hu YH, Yan JH, Xu GZ, Cai WM, Wu XL, Cao DX, Gu XZ: Analysis of 1379 patients with nasopharyngeal carcinoma treated by radiation. Cancer 1988, 61:1117–1124. 12. Ma J, Mai H, Hong M, Min HQ, Mao ZD, Cui NJ, Lu TX, Mo HY: Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma. J Clin Oncol 2001, 19:1350–1357. 13. Zeng Y, Zhang LG, Wu YC, Huang YS, Huang NQ, Li JY, Wang YB, Jiang MK, Fang Z, Meng NN: Prospective studies on nasopharyngeal carcinoma in Epstein-Barr virus IgA/VCA antibody-positive persons in Wuzhou City, China. Int J Cancer 1985, 36(5):545–547. 15. 14. Ji MF, Yu YL, Cheng WM, Zong YS, Ng PS, Chua DT, Ng MH: Detection of stage I nasopharyngeal carcinoma by serologic screening and clinical examination. Chin J Cancer 2011, 30:120–123. 15. Chan JKC, Pilch BZ, KUO TT, Wenig BM, Lee AWM: World Health Organization: Pathology and Genetics Head and Neck Tumours. In Classification of Tumours. Tumours of the nasopharynx. Edited by Barnes L, Eveson JW, Reichart P, Sidransky D. Lyon:; 2005:81–106. 16. Gulley ML: Molecular diagnosis of Epstein-Barr virus-related diseases. J Mol Diagn 2001, 3(1):1–10. 17. Marks JE, Phillips JL, Menck HR: The National Cancer Database report on the relationship of race and national origin to the histology of nasopharyngeal carcinoma. Cancer 1998, 83:582–588. 18. Herrmann K, Niedobitek G: Epstein-Barr virus-associated carcinomas: facts and fiction. J Pathol 2003, 199:140–145. 19. Brooks L, Yao QY, Rickinson AB, Young LS: Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts. J Virol 1992, 66:2689–2697. 20. Wang D, Liebowitz D, Kieff E: An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells. Cell 1985, 43:831–840. 21. Mainou BA, Raab-Traub N: LMP1 strain variants: biological and molecular properties. J Virol 2006, 80:6458–6468. 22. Fahraeus R, Fu HL, Ernberg I, Finke J, Rowe M, Klein G, Falk K, Nilsson E, Yadav M, Busson P, Tursz T, Kallin B: Expression of Epstein-Barr virus- encoded proteins in nasopharyngeal carcinoma. Int J Cancer 1988, 42:329–338. 23. Tsang RK, Vlantis AC, Ho RW, Tam JS, To KF, van Hasselt CA: Sensitivity and specificity of Epstein-Barr virus IGA titer in the diagnosis of nasopharyngeal carcinoma: a three-year institutional review. Head Neck 2004, 26(7):598–602. 24. Cheng WM, Chan KH, Chen HL, Luo RX, Ng SP, Luk W, Zheng BJ, Ji MF, Liang JS, Sham JST, Wang DK, Zong YS, Ng MH: Assessing the risk of nasopharyngeal carcinoma on the basis of EBV antibody spectrum. Int J Cancer 2002, 97(4):489–492. 25. Shotelersuk K, Khorprasert C, Sakdikul S, Pornthanakasem W, Voravud N, Mutirangura A: Epstein-Barr virus DNA in serum/plasma as a tumor marker for nasopharyngeal cancer. Clin Cancer Res 2000, 6:1046–1051. 26. Lo YM, Chan LY, Chan AT, Leung SF, Lo KW, Zhang J, Lee JC, Hjelm NM, Johnson PJ, Huang DP: Quantitative and temporal correlation between circulating cell-free Epstein-Barr virus DNA and tumor recurrence in nasopharyngeal carcinoma. Cancer Res 1999, 59:5452–5455.