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Fulltext Systematic comparison of plasma EBV DNA, anti-EBV antibodies and miRNA levels for early detection and prognosis of nasopharyngeal carcinoma

Tan LP, Tan GW, Sivanesan VM, Goh SL, Ng XJ, Lim CS, et al.

Int J Cancer, 2020 04 15;146(8):2336-2347.
PMID: 31469434 DOI: 10.1002/ijc.32656

Nasopharyngeal carcinoma (NPC) is originated from the epithelial cells of nasopharynx, Epstein-Barr virus (EBV)-associated and has the highest incidence and mortality rates in Southeast Asia. Late presentation is a common issue and early detection could be the key to reduce the disease burden. Sensitivity of plasma EBV DNA, an established NPC biomarker, for Stage I NPC is controversial. Most newly reported NPC biomarkers have neither been externally validated nor compared to the established ones. This causes difficulty in planning for cost-effective early detection strategies. Our study systematically evaluated six established and four new biomarkers in NPC cases, population controls and hospital controls. We showed that BamHI-W 76 bp remains the most sensitive plasma biomarker, with 96.7% (29/30), 96.7% (58/60) and 97.4% (226/232) sensitivity to detect Stage I, early stage and all NPC, respectively. Its specificity was 94.2% (113/120) against population controls and 90.4% (113/125) against hospital controls. Diagnostic accuracy of BamHI-W 121 bp and ebv-miR-BART7-3p were validated. Hsa-miR-29a-3p and hsa-miR-103a-3p were not, possibly due to lower number of advanced stage NPC cases included in this subset. Decision tree modeling suggested that combination of BamHI-W 76 bp and VCA IgA or EA IgG may increase the specificity or sensitivity to detect NPC. EBNA1 99 bp could identify NPC patients with poor prognosis in early and advanced stage NPC. Our findings provided evidence for improvement in NPC screening strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity or specificity and testing biomarkers from single sampled specimen to avoid logistic problems of resampling.

Matched MeSH terms: Nasopharyngeal Neoplasms/virology*
Fulltext The distinctive profile of risk factors of nasopharyngeal carcinoma in comparison with other head and neck cancer types

Abdulamir AS, Hafidh RR, Abdulmuhaimen N, Abubakar F, Abbas KA

BMC Public Health, 2008;8:400.
PMID: 19055849 DOI: 10.1186/1471-2458-8-400

Nasopharyngeal carcinoma (NPC) and other head and neck cancer (HNCA) types show a great epidemiological variation in different regions of the world. NPC has multifactorial etiology and many interacting risk factors are involved in NPC development mainly Epstein Barr virus (EBV). There is a need to scrutinize the complicated network of risk factors affecting NPC and how far they are different from that of other HNCA types.

Matched MeSH terms: Nasopharyngeal Neoplasms/virology*
Fulltext Whole-genome profiling of nasopharyngeal carcinoma reveals viral-host co-operation in inflammatory NF-κB activation and immune escape

Bruce JP, To KF, Lui VWY, Chung GTY, Chan YY, Tsang CM, et al.

Nat Commun, 2021 07 07;12(1):4193.
PMID: 34234122 DOI: 10.1038/s41467-021-24348-6

Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs. A similar spectrum of somatic aberrations and viral gene expression undermine innate immunity in 79% of cases and adaptive immunity in 47% of cases; mechanisms by which NPC may evade immune surveillance despite its pro-inflammatory phenotype. Additionally, genomic changes impairing TGFBR2 promote oncogenesis and stabilize EBV infection in tumor cells. Fine-mapping of CDKN2A/CDKN2B deletion breakpoints reveals homozygous MTAP deletions in 32-34% of NPCs that confer marked sensitivity to MAT2A inhibition. Our work concludes that NPC is a homogeneously NF-κB-driven and immune-protected, yet potentially druggable, cancer.

Matched MeSH terms: Nasopharyngeal Neoplasms/virology
p53 and nasopharyngeal carcinoma: a Malaysian study

Hoe SL, Lee ES, Khoo AS, Peh SC

Pathology, 2009;41(6):561-5.
PMID: 19900105

AIMS: Nasopharyngeal carcinoma (NPC) is a common malignancy among men in Malaysia. To determine the role of p53 in NPC, we screened for p53 mutations and evaluated the protein expression levels in samples from local patients with NPC.
METHODS: Fifty-three formalin-fixed, paraffin-embedded nasopharyngeal carcinoma tissue blocks were chosen for this study. The presence of Epstein-Barr virus (EBV) was determined by in situ hybridisation using an EBER probe. p53 protein expression was detected using immunohistochemistry. Simultaneously, amplifications by PCR were performed for p53 exons 5 to 8, followed by mutation screening via single strand conformation polymorphism (SSCP). Sequencing of all the four exons was performed in five samples with mobility shift. To rule out false negative results by SSCP, 13 samples with p53 overexpression and five samples with low p53 expression were randomly selected and sequenced.
RESULTS: There was no mutation found in exons 5 to 8 in all the samples despite 46 (87%) of them having high p53 levels. EBV was detected in 51 (96%) out of 53 samples. There was no statistically significant association between p53 expression level and EBV presence.
CONCLUSIONS: High-intensity staining for p53 by immunohistochemistry was common in our series of NPC tissue samples but was not associated with 'hot spot' mutations of exons 5-8 of the gene. We did not find a significant relationship between the expression level of p53 and presence of EBV. Our study confirms that mutation of the DNA-binding domain of p53 is rare in NPC.

Matched MeSH terms: Nasopharyngeal Neoplasms/virology