Biomarkers in nasopharyngeal carcinoma and ionizing radiation

Cancer of the nasopharynx is an epithelial cancer developed in the retro-nasal area in the nasal cavity. Nasopharyngeal carcinoma (NPC) is prevalent in the endemic regions including Southern China and Southeast Asia. The primary tumor of NPC is small and usually causes no symptoms. Patients often present with bilateral glands enlargement and local/regional lymph node metastasis leading to poor prognosis and local control rate. Therefore, there is a desperate need to develop early diagnosis method to improve the treatment outcome. Detection of EBV-derived biomarkers in tissues and EBV DNA in the peripheral blood of NPC patients opens up the possibility to monitor the disease using molecular markers with high sensitivity. Among the biomarkers in tissue, in situ hybridization for EBER remains to be the most efficient and reliable way because EBER is the most abundantly expressed viral transcript. In addition to diagnosis value, EBER, EBNA1, and LMP1 levels in tissue after radiation therapy could serve as biomarkers to evaluate response to radiotherapy. In light of the detection of EBV DNA in plasma, serum, nasal brush, and saliva, EBV DNA is particularly useful for periodic monitoring of NPC patients. A systematic review has revealed that circulating EBV DNA could be applied as noninvasive diagnostic biomarker for NPC. Moreover, the close association of circulating EBV DNA with the clinical outcomes of treatment provided new tool to predict the treatment outcome. Nevertheless, circulating EBV DNA was not detectable in all the undifferentiated NPC patients, and EBV latent infection was not associated with WHO-1 NPC, which limits the utility of EBV DNA. Further studies are warranted to identify complementary biomarkers originating from the human cancer cells to overcome the limitation of EBV-based biomarkers in NPC screening and monitoring treatment outcome.