Detection Of Nasopharyngeal Carcinoma Research Articles

Fiber-Optic Raman Spectroscopy with Nature-Inspired Genetic Algorithms Enhances Real-Time in Vivo Detection and Diagnosis of Nasopharyngeal Carcinoma.

Raman spectroscopy is an optical vibrational spectroscopic technique capable of probing specific biochemical structures and conformation of tissue and cells in biomedical systems. This work aims to assess the clinical utility of a fiber-optic Raman spectroscopy with nature-inspired genetic algorithms for enhancing in vivo detection and diagnosis of nasopharyngeal carcinoma (NPC) patients. The Raman diagnostic platform is developed based on simultaneous fingerprint (FP) and high-wavenumber (HW) fiber-optic Raman endoscopy associated with genetic algorithms-partial least-squares-linear discriminant analysis (GA-PLS-LDA). A total of 2126 in vivo FP/HW Raman spectra (598 NPC, 1528 normal) acquired from 113 tissue sites of 14 NPC patients and 48 healthy subjects during nasopharyngeal endoscopic examinations. Distinct Raman peaks have been identified (853 cm-1 - proteins, 1209 cm-1 - phenylalanine, 1265 cm-1 - proteins, 1335 cm-1 - proteins and nucleic acids, 1554 cm-1 - tryptophan, porphyrin, 2885 cm-1 - lipids, 2940 cm-1 - proteins, 3009 cm-1 - lipids, and 3250 cm-1 - water) that are related to the significant biochemical changes ( p < 1 × 10-5) in NPC compared to normal tissue. Raman diagnostic performance is evaluated through the leave-one-object (tissue site)-out cross-validation (LOOCV) method. A statistically significant GA-PLS-LDA model ( p < 1 × 10-5) on FP/HW Raman yields a CV diagnostic accuracy of 98.23% (111/113), sensitivity of 93.33% (28/30), and specificity of 100% (83/83) for NPC classification. This work demonstrates that the fiber-optic FP/HW Raman diagnostic platform developed has great promise for improving real-time in vivo detection and diagnosis of NPC at the molecular level during clinical nasopharyngeal endoscopy.

Cell-free DNA methylation markers for noninvasive early detection of nasopharyngeal carcinoma.

e14537 Background: Nasopharyngeal carcinoma (NPC) is one of the most prevalent malignancies among populations native to Southeast Asia, the Mediterranean Basin and the Arctic. Early diagnosis of NPC is predicted to improve survival. The identification of cancer-specific DNA methylation patterns of cell-free DNA (cfDNA) isolated from blood samples is an established approach for detecting various cancers. In the present study, we evaluated the performance characteristics of a previously identified NPC methylation marker panel for the diagnosis of nasopharyngeal carcinoma. Methods: Retrospective samples were obtained for 168 subjects, including: 59 subjects diagnosed with NPC (Stage I to IV), 14 subjects diagnosed with benign nasopharyngeal disease and 43 healthy subjects. In addition, sample were obtained for 52 subjects diagnosed with breast, colorectal, liver or lung cancer. Samples were provided to the laboratory blinded for DNA methylation analysis by using the IvyGene Platform. Results: A total of 57 of the 59 samples drawn from subjects with NPC were correctly identified for an overall sensitivity of 97%, with little difference between the sensitivity of detecting Stage I to Stage IV nasopharyngeal carcinoma (range 92% to 100%). For subjects diagnosed with other cancers, 85% of colorectal cancer samples, 82% of lung cancer samples, 93% of both breast cancer and liver cancer samples, were correctly identified as negative for NPC, for a total calculated analytical specificity of 86%. Additionally, all 43 samples drawn from healthy donors and 14 samples drawn from subjects diagnosed with benign nasopharyngeal disease were correctly identified as negative for nasopharyngeal carcinoma for a combined specificity of 100%. Conclusions: The NPC methylation panel was demonstrated to be both sensitive and specific for the detection of nasopharyngeal carcinoma. The potential of cfDNA methylation markers for the early detection of nasopharyngeal carcinoma is predicted to improve patient outcomes through earlier detection of the disease.

Genome-wide study of salivary microRNAs as potential noninvasive biomarkers for detection of nasopharyngeal carcinoma.

e17535 Background: Since recent studies reported that blood-based microRNAs (miRNAs) could detect cancers and predict prognosis, a new field has been opened for circulating miRNAs as potential biomarkers in cancers. In this pilot study, we evaluated to our knowledge for the first time whether salivary miRNAs might be applicable as innovative biomarkers for Nasopharyngeal carcinoma (NPC) detection. Methods: By high throughput label-free microarray contained 2025 human miRNA probes, 12 down-regulated miRNAs from saliva samples from 22 newly diagnosed NPC patients and 25 healthy controls were selected. Then, their target genes enriched by gene ontology and pathway were used to construct a regulatory and interaction networks. The receiver operating characteristic analyses (ROC) and logistic regression were calculated to assess discriminatory accuracy. Results: Advanced bioinformatics analysis was conducted to understand the most significant hub gene is TP53 that probably regulated by the 12 dysregulated miRNAs. The ROC including the 12 miRNAs as well as the 6 significant deregulated miRNAs separated NPC patients from healthy controls with a very high (areas under the receiver operating characteristic curve [AUC] = 0.999, sensitivity = 100.00%, specificity = 96.00%) and high accuracy (AUC = 0.941, sensitivity = 95.45%, specificity = 80.00%), respectively. Conclusions: Differentially expressed miRNAs might play critical roles in NPC by regulating their target genes, and may have the potential to become diagnostic biomarkers.

Accuracy of Raman spectroscopy in discrimination of nasopharyngeal carcinoma from normal samples: a systematic review and meta-analysis.

The aim of this review was to systematically evaluate the diagnostic accuracy of Raman spectroscopy (RS) in the identification of nasopharyngeal carcinomas from normal nasopharyngeal tissue. We searched six databases (PubMed, Embase, Cochrane Library, Web of Science, Scopus and CNKI) up to September 2018 for all published studies that assessed the diagnostic accuracy of RS in the detection of nasopharyngeal carcinomas. Non-qualifying studies were screened out in accordance with the specified exclusion criteria and relevant information about the diagnostic performance of RS extracted. A random effects model was adopted to calculate the pooled sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR, respectively), diagnostic threshold and diagnostic odds ratio (DOR). Additionally, we conducted a summary receiver-operating characteristic (SROC) curve analysis and threshold analysis, reporting area under the curve (AUC) to evaluate the overall performance of RS. Three studies examined RS analysis in vivo, the pooled sensitivity and specificity of RS of which were 0.90 and 0.91, respectively, with an AUC of 0.9617. Eighteen studies assessed ex vivo samples, for which RS exhibited particularly high accuracy for the analysis of blood plasma. RS was demonstrated to be a reliable technique for the detection of nasopharyngeal carcinoma with high accuracy, but additional studies are required to improve its performance and expand its application in ex vivo detection.

Cost-effectiveness of Screening for Nasopharyngeal Carcinoma among Asian American Men in the United States.

Most patients with nasopharyngeal carcinoma (NPC) in the United States are diagnosed with stage III-IV disease. Screening for NPC in endemic areas results in earlier detection and improved outcomes. We examined the cost-effectiveness of screening for NPC with plasma Epstein-Barr virus DNA among Asian American men in the United States. We used a Markov cohort model to estimate discounted life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios for screening as compared with usual care without screening. The base case analysis considered onetime screening for 50-year-old Asian American men. Confirmatory testing was magnetic resonance imaging and nasopharyngoscopy. Cancer-specific outcomes, health utility values, and costs were determined from cancer registries and the published literature. For Asian American men, usual care without screening resulted in the detection of NPC at stages I, II, III-IVB, and IVC among 6%, 29%, 54%, and 11% of those with cancer, respectively, whereas screening resulted in earlier detection with a stage distribution of 43%, 24%, 32%, and 1%. This corresponded to an additional 0.00055 QALYs gained at a cost of $63 per person: an incremental cost of $113,341 per QALY gained. In probabilistic sensitivity analysis, screening Asian American men was cost-effective at $100,000 per QALY gained in 35% of samples. Although screening for NPC with plasma Epstein-Barr virus DNA for 50-year-old Asian American men may result in earlier detection, in this study it was unlikely to be cost-effective. Screening may be reasonable for certain subpopulations at higher risk for NPC, but clinical studies are necessary before implementation.

A novel and non-invasive approach utilising nasal washings for the detection of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an epithelial cancer of the nasopharynx which is highly associated with Epstein–Barr virus (EBV). Worldwide, most of the top 20 countries with the highest incidence and mortality rates of NPC are low‐ and middle‐income countries. Many studies had demonstrated that EBV could be detected in the tissue, serum and plasma of NPC patients. In this study, we explored the potential of assays based on non‐invasive nasal washings (NW) as a diagnostic and prognostic tool for NPC. A total of 128 patients were evaluated for NW EBV DNA loads and a subset of these samples were also tested for 27 EBV and human miRNAs shortlisted from literature. EBV DNA and seven miRNAs showed area under the receiver operating characteristic curve (AUC) values of more than 0.7, suggestive of their potential utility to detect NPC. Logistic regression analyses suggested that combination of two NW assays that test for EBNA‐1 and hsa‐miR‐21 had the best performance in detecting NPC. The trend of NW EBV DNA load matched with clinical outcome of 71.4% (10 out of 14) NPC patients being followed‐up. In summary, the non‐invasive NW testing panel may be particularly useful for NPC screening in remote areas where healthcare facilities and otolaryngologists are lacking, and may encourage frequent testing of individuals in the high risk groups who are reluctant to have their blood tested. However, further validation in an independent cohort is required to strengthen the utility of this testing panel as a non‐invasive detection tool for NPC.

Detection of Epstein-Barr virus (EBV)-encoded microRNAs in plasma of patients with nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) latently infected by Epstein-Barr virus (EBV) expresses 40 EBV BART microRNAs (miRNAs). Difference in diagnostic efficacy of these miRNAs on NPC detection was observed. Here, we performed a comprehensive evaluation on the efficacy of these miRNAs. Quantitative polymerase chain reaction was performed on plasma nucleic acid isolated from patients with NPC and noncancer donors. For primary NPC, BART2-5P, BART6-3P, BART7-3P, BART7-5P, BART9-5P, BART11-3P, BART17-5P, and BART19-5P were significantly elevated. For recurrent NPC, plasma levels of BART2-3P, BART2-5P, BART5-3P, BART5-5P, BART6-3P, BART8-3P, BART9-5P, BART17-5P, BART19-3P, and BART20-3P were significantly increased. Area under curve (AUC) analysis showed that BART19-5P had the best performance to identify NPC which was serologically EBV DNA undetectable. For recurrent NPC, BART8-3P and BART10-3P had highest AUC value for identifying cancer in EBV DNA undetectable plasma. Our data supported the use of circulating EBV miRNAs in NPC and recurrent NPC detection.

Plasma microRNA expression signature involving miR-548q, miR-630 and miR-940 as biomarkers for nasopharyngeal carcinoma detection.

Increasing studies have identified a series of circulating mircoRNAs (miRNAs) as biomarkers for disease detection due to their stability in the blood. The aim of the present study was to identify specific plasma miRNAs as potential biomarkers for nasopharyngeal carcinoma (NPC) detection. Relative public microarray data were obtained and analyzed for screening of the plasma differentially expressed miRNAs (DEMs) between NPC patients and controls. This study contained two phases: a screening phase and a validation one. Logistic regression and receiver operating characteristics curve (ROC) analyses were used to identify DEM signatures. Moreover, targeted genes of the selected DEMs were predicted and their functions were annotated by using bioinformatic analysis. Both the screening and the validation phases showed that three miRNAs (miR-548q, miR-630 and miR-940) in the plasma of NPC patients were up-regulated compared to those of controls. They can be used as biomarkers for discriminating NPC patients from non-cancerous controls. Moreover, we found a classifier including only two miRNAs (miR-548q and miR-940) that can be used as a diagnostic signature for NPC, achieving an area under curve (AUC) of 0.972, a sensitivity of 0.94, and a specificity of 0.925. The present study demonstrated that three miRNAs (miR-548q, miR-630 and miR940) might be novel and useful biomarkers for NPC detection. A two-miRNA signature (miR-548q and miR940) may be considered as a better biomarker for NPC detection with relatively high sensitivity and specificity. Future studies with large sample sizes are needed for further validation.

Vesicle-bound EBV-BART13-3p miRNA in circulation distinguishes nasopharyngeal from other head and neck cancer and asymptomatic EBV-infections.

Cell‐free microRNA (miRNA) in biofluids released by tumors in either protein or vesicle‐bound form, represent promising minimally‐invasive cancer biomarkers. However, a highly abundant non‐tumor background in human plasma and serum complicates the discovery and detection of tumor‐selective circulating miRNAs. We performed small RNA sequencing on serum and plasma RNA from Nasopharyngeal Carcinoma (NPC) patients. Collectively, Epstein Barr virus‐encoded miRNAs, more so than endogenous miRNAs, signify presence of NPC. However, RNAseq‐based EBV miRNA profiles differ between NPC patients, suggesting inter‐tumor heterogeneity or divergent secretory characteristics. We determined with sensitive qRT‐PCR assays that EBV miRNAs BART7‐3p, BART9‐3p and BART13‐3p are actively secreted by C666.1 NPC cells bound to extracellular vesicles (EVs) and soluble ribonucleoprotein complexes. Importantly, these miRNAs are expressed in all primary NPC tumor biopsies and readily detected in nasopharyngeal brushings from both early and late‐stage NPC patients. Increased levels of BART7‐3p, BART9‐3p and particularly BART13‐3p, distinguish NPC patient sera from healthy controls. Receiver operating characteristic curve analysis using sera from endemic NPC patients, other head and neck cancers and individuals with asymptomatic EBV‐infections reveals a superior diagnostic performance of EBV miRNAs over anti‐EBNA1 IgA serology and EBV‐DNA load (AUC 0.87–0.96 vs 0.86 and 0.66 respectively). The high specificity of circulating EBV‐BART13‐3p (97%) for NPC detection is in agreement with active secretion from NPC tumor cells. We conclude EV‐bound BART13‐3p in circulation is a promising, NPC‐selective, biomarker that should be considered as part of a screening strategy to identify NPC in endemic regions.

Diagnosis of nasopharyngeal carcinoma from serum samples using hyperspectral imaging combined with a chemometric method.

Diagnosing nasopharyngeal carcinoma (NPC) is a significant challenge because of the highly complex process. We proposed an approach to diagnose NPC serum using a combination of hyperspectral imaging and weight-based principal component analysis. Samples were prepared by pressing boric acid into pellets for use as the sera substrate. The sera, collected from 100 healthy volunteers and 60 NPC patients, was dripped onto the surface of the substrate for hyperspectral imaging. The characteristic spectral bands were selected based on the variable weight obtained from a support vector machine (SVM) model, using principal component analysis (PCA) to reduce the dimension in the extracted bands. Obtained results show that the accuracy rate, sensitivity, and specificity between the NPC sera and the sera of the healthy controls reached extremely high levels of 99.15%, 98.79%, and 99.36%, respectively. For the model's consistency evaluation, we found that the Kappa and area under the curve (AUC) of the receiver operating characteristic (ROC) curve were 0.99 and 0.98, respectively. These results suggest that the developed approach could serve as a noninvasive diagnostic and screening tool for highly accurate and consistent detection of NPC. Hence, a combination of hyperspectral imaging (HSI) and a weighted principal component analysis (WPCA)-SVM model represents a powerful and promising tool for NPC diagnosis.

MiR-639 is associated with advanced cancer stages and promotes proliferation and migration of nasopharyngeal carcinoma.

Early detection of nasopharyngeal carcinoma (NPC) is of vital importance for improving prognosis and survival rates. MicroRNA (miRNA) are a class of short and non-coding RNA molecules that are capable of inhibiting the translation of mRNA of target genes. Previous studies have revealed that miRNA are involved in tumorigenesis and cancer development. The RNase-resistance of circulating miRNA have made them valuable non-invasive biomarkers, and has therefore drawn particular attention to their therapeutic potential. The aim of the present study was to investigate the expression of the previously uncharacterized miR-639 in NPC. In a study population of 139 patients, higher expression of miR-639 was associated with metastasis, more advanced cancer stages, and lower disease-free survival rates. In vitro experiments involving transfection of human NPC C666-1 and NPC/HK1 cell lines with miR-639 mimics and antagomir indicated that overexpressing miR-639 promoted cell proliferation and migration, suppression of miR-639 inhibited proliferation and migration. The present study provides evidence that miR-639 is differentially expressed in NPC tissues of varying cancer stages, and suggests that quantifying circulating miR-639 may be of importance for non-invasive diagnosis and prognostic evaluation, and may have potential therapeutic utility.

Epigenetic Alterations of Wnt Signaling Pathways in Nasopharyngeal Carcinoma

The purpose of this study is to discuss the epigenetic alterations of Wnt signaling pathways in nasopharyngeal carcinoma. Methylomic analyses have revealed that in nasopharyngeal carcinoma, numerous genes in Wnt signaling pathways are hypermethylated, which results in the inactivation of tumor-suppressor genes and aberrant activation of Wnt signaling. Reactivation of the tumor-suppressor genes by demethylation or ectopic expression inhibits the proliferation, metastasis, or stemness of nasopharyngeal carcinoma cells. Epigenetic alterations of Wnt signaling pathways contribute to cancer-cell stemness, epithelial-mesenchymal transition, and metastasis during the tumorigenesis of nasopharyngeal carcinoma. Methylated DNAs of Wnt signaling factors hold considerable potential as candidate biomarkers for early detection of nasopharyngeal carcinoma.

A real time computer aided object detection of nasopharyngeal carcinoma using genetic algorithm and artificial neural network based on Haar feature fear

Nasopharyngeal carcinoma (NPC) is a serious disease with diverse prognoses and the diffusive development of the tumors further complicates the diagnosis. However, in most cases, surgery is performed by resecting the tumor that decides the life expectancy of a patient. Certainly, the graphical portrayal is a fundamental factor to distinguish and examine an NPC tumor; and, the exact nasopharyngeal carcinoma perception remains an important errand. It is crucial to improve the extent of resection for the irregular tissues while sparing the normal ones. There are several methods to envision the nasopharyngeal carcinoma, but the main problem with these strategies is the inability to imagine the border points of the nasopharyngeal tumor accurately in detail. In addition, the inability to separate the normal tissues from the undesirable ones prompts the assessment and calculation of a wrong tumor measure. NPC diagnosis is a difficult and challenging process owing to the possible shapes and regions of tumors and intensity of the images. The pathological identification of the nasopharyngeal carcinoma and comparing typical and anomalous tissues require a set of scientific strategies for the extraction of features. The aim of this paper was to outline and assess a novel method using machine learning approaches based on genetic algorithm for NPC feature selection and artificial neural networks for an automated NPC detection of the NPC tissues from endoscopic images. The proposed approach was validated by comparing the number of NPC identified through this technique against the manual checking by the ENT specialists. The classifier lists a high precision of 96.22%, the sensitivity of 95.35%, and specificity of 94.55%. Additionally, the feature chosen process makes the Artificial Neural Networks classifier straightforward and more efficient.

A meta-analysis of narrow-band imaging for the diagnosis of primary nasopharyngeal carcinoma

Background: Narrow band imaging (NBI), an endoscopic technique featuring an augmented definition of microvasculature and mucosal patterns. NBI is increasingly advocated as a tool to characterize neoplasia and intestinal metaplasia in endoscopic standards, such as for colorectal polyps and tumors. Recently NBI has also been studied in the detection of Nasopharyngeal Carcinoma (NPC). Here we aimed to assess the diagnostic utility of NBI for the diagnosis of NPC. Methods: A meta-analysis of studies comparing narrow-band imaging and white light endoscopy in the diagnosis of primary nasopharyngeal carcinoma was performed. The review process involved two independent investigators. The databases used were MEDLINE, PubMed, the Cochrane library, Embase, and the Web of Science. Statistical analysis was performed with OpenMetaAnalyst, MetaDiSc version 1.4, and Medcalc version 17.9.7. Results: Five studies including 2480 patients were included. The sensitivity and specificity for narrow-band imaging were 0.90 (0.73-0.97) and 0.95 (0.81-0.99) respectively. The positive likelihood ratio and negative likelihood ratio were 18.82 (0.31-82.1) and 0.08 (0.02-0.31). For white light endoscopy, the sensitivity and specificity were 0.77 (0.58-0.89) and 0.91 (0.79-0.96). The positive likelihood ratio was 7.61 (3.61-16.04), and the negative likelihood ratio was 0.21 (0.11-0.39). The odds ratio for detection rates between narrow-band imaging and white light endoscopy was 4.29 (0.56-33.03, p = 0.16). Area under the curve for narrow-band imaging was 0.98 (SE: 0.02), and for white light it was 0.93 (SE: 0.03). There was no significant difference in the receiver operating characteristic curves between the two modalities (p = 0.14). Conclusion: Narrow-band imaging showed a higher sensitivity and positive likelihood ratio for the diagnosis of nasopharyngeal carcinoma. However, there was no significant difference in detection rates compared to white light endoscopy. Further investigation with a uniform diagnostic criteria and terminology is needed for narrow-band imaging in the diagnosis of nasopharyngeal carcinoma.

A meta-analysis of narrow-band imaging for the diagnosis of primary nasopharyngeal carcinoma.

Background: Narrow band imaging (NBI), an endoscopic technique featuring an augmented definition of microvasculature and mucosal patterns. NBI is increasingly advocated as a tool to characterize neoplasia and intestinal metaplasia in endoscopic standards, such as for colorectal polyps and tumors. Recently NBI has also been studied in the detection of Nasopharyngeal Carcinoma (NPC). Here we aimed to assess the diagnostic utility of NBI for the diagnosis of NPC. Methods: A meta-analysis of studies comparing narrow-band imaging and white light endoscopy in the diagnosis of primary nasopharyngeal carcinoma was performed. The review process involved two independent investigators. The databases used were MEDLINE, PubMed, the Cochrane library, Embase, and the Web of Science. Statistical analysis was performed with OpenMetaAnalyst, MetaDiSc version 1.4, and Medcalc version 17.9.7. Results: Five studies including 2480 patients were included. The sensitivity and specificity for narrow-band imaging were 0.90 (0.73-0.97) and 0.95 (0.81-0.99) respectively. The positive likelihood ratio and negative likelihood ratio were 18.82 (0.31-82.1) and 0.08 (0.02-0.31). For white light endoscopy, the sensitivity and specificity were 0.77 (0.58-0.89) and 0.91 (0.79-0.96). The positive likelihood ratio was 7.61 (3.61-16.04), and the negative likelihood ratio was 0.21 (0.11-0.39). The odds ratio for detection rates between narrow-band imaging and white light endoscopy was 4.29 (0.56-33.03, p = 0.16). Area under the curve for narrow-band imaging was 0.98 (SE: 0.02), and for white light it was 0.93 (SE: 0.03). There was no significant difference in the receiver operating characteristic curves between the two modalities (p = 0.14). Conclusion: Narrow-band imaging showed a higher sensitivity and positive likelihood ratio for the diagnosis of nasopharyngeal carcinoma. However, there was no significant difference in detection rates compared to white light endoscopy. Further investigation with a uniform diagnostic criteria and terminology is needed for narrow-band imaging in the diagnosis of nasopharyngeal carcinoma.

Identification of a Novel, EBV-Based Antibody Risk Stratification Signature for Early Detection of Nasopharyngeal Carcinoma in Taiwan.

Background Epstein-Barr virus (EBV) is necessary for the development of nasopharyngeal carcinoma (NPC). By adulthood, approximately 90% of individuals test EBV-positive, but only a fraction develop cancer. Factors that identify which individuals are most likely to develop disease, including differential antibody response to the virus, could facilitate detection at early stages when treatment is most effective.Methods We measured anti-EBV IgG and IgA antibody responses in 607 Taiwanese individuals. Antibodies were measured using a custom protein microarray targeting 199 sequences from 86 EBV proteins. Variation in response patterns between NPC cases and controls was used to develop an antibody-based risk score for predicting NPC. The overall accuracy [area under the curve (AUC)] of this risk score, and its performance relative to currently used biomarkers, was evaluated in two independent Taiwanese cohorts.Findings Levels of 60 IgA and 73 IgG anti-EBV antibodies differed between stage I/IIa NPC cases and controls (P < 0.0002). Risk prediction analyses identified antibody targets that best discriminated NPC status-BXLF1, LF2,BZLF1, BRLF1, EAd, BGLF2, BPLF1, BFRF1, and BORF1. When combined with currently used VCA/EBNA1 IgA biomarkers, the resulting risk score predicted NPC with 93% accuracy (95% CI, 87%-98%) in the general Taiwanese population, a significant improvement beyond current biomarkers alone (82%; 95% CI, 75%-90%, P ≤ 0.01). This EBV-based risk score also improved NPC prediction in genetically high-risk families (89%; 95% CI, 82%-96%) compared with current biomarkers (78%; 95% CI, 66%-90%, P ≤ 0.03).Interpretation We identified NPC-related differences in 133 anti-EBV antibodies and developed a risk score using this microarray dataset that targeted immune responses against EBV proteins from all stages of the viral life cycle, significantly improving the ability to predict NPC. Clin Cancer Res; 24(6); 1305-14. ©2017 AACR.

MR Imaging Criteria for the Detection of Nasopharyngeal Carcinoma: Discrimination of Early-Stage Primary Tumors from Benign Hyperplasia.

MR imaging can detect nasopharyngeal carcinoma that is hidden from endoscopic view, but for accurate detection carcinoma confined within the nasopharynx (stage T1) must be distinguished from benign hyperplasia of the nasopharynx. This study aimed to document the MR imaging features of stage T1 nasopharyngeal carcinoma and to attempt to identify features distinguishing it from benign hyperplasia. MR images of 189 patients with nasopharyngeal carcinoma confined to the nasopharynx and those of 144 patients with benign hyperplasia were reviewed and compared in this retrospective study. The center, volume, size asymmetry (maximum percentage difference in area between the right and left nasopharyngeal halves), signal intensity asymmetry, deep mucosal white line (greater contrast enhancement along the deep tumor margin), and absence/distortion of the adenoidal septa were evaluated. Differences were assessed with logistic regression and the χ2 test. The nasopharyngeal carcinoma center was lateral, central, or diffuse in 134/189 (70.9%), 25/189 (13.2%), and 30/189 (15.9%) cases, respectively. Nasopharyngeal carcinomas involving the walls showed that a deep mucosal white line was present in 180/183 (98.4%), with a focal loss of this line in 153/180 (85%) cases. Adenoidal septa were absent or distorted in 111/111 (100%) nasopharyngeal carcinomas involving the adenoid. Compared with benign hyperplasia, nasopharyngeal carcinoma had a significantly greater volume, size asymmetry, signal asymmetry, focal loss of the deep mucosal white line, and absence/distortion of the adenoidal septa (P < .001). Although size asymmetry was the most accurate criterion (89.5%) for nasopharyngeal carcinoma detection, use of this parameter alone would have missed 11.9% of early-stage T1 nasopharyngeal carcinomas. MR imaging features can help distinguish stage T1 nasopharyngeal carcinoma from benign hyperplasia in most cases.

Abnormally expressed microRNA as auxiliary biomarkers for nasopharyngeal carcinoma: A meta‑analysis

Aberrant expression of microRNA (miRNA) has been highlighted as a helpful indicator to aid in nasopharyngeal carcinoma (NPC) diagnosis. The present meta-analysis aimed to validate the efficacy of miRNA as potential biomarkers for NPC detection. Publication searches were conducted on the online PubMed and EMBASE databases from inception to June 2016. A bivariate meta-analysis was performed to generate the diagnostic parameters based on Meta-Disc 1.4 and Stata 12.0 programs. Sensitivity analysis and meta-regression tests were applied to trace heterogeneity sources among eligible studies. A total of six studies comprising 528 patients with NPC and 252 matched controls were enrolled. Results from the present meta-analysis demonstrated that miRNA testing achieved a pooled sensitivity of 0.78 [95% confidence interval (CI), 0.70-0.84] and specificity of 0.79 (95% CI, 0.73-0.84) in confirming NPC, corresponding to an area under the curve (AUC) value of 0.85. Additionally, the pooled diagnostic odds ratio was estimated to be 9.01 (95% CI, 5.62-14.44), along with a positive likelihood ratio of 2.81 (95% CI, 2.19-3.61) and negative likelihood ratio of 0.35 (95% CI, 0.28-0.44). Additionally, the stratified analyses revealed that paralleled testing of miRNA sustained a pooled accuracy superior compared with that of single miRNA testing (sensitivity, 0.88 vs. 0.70; specificity, 0.85 vs. 0.69; AUC, 0.95 vs. 0.75). Testing of miRNA harbors a moderate diagnostic efficacy and is acceptable as an auxiliary biomarker for NPC diagnosis.

Noninvasive detection of nasopharyngeal carcinoma based on saliva proteins using surface-enhanced Raman spectroscopy

The present study evaluated the capability of saliva analysis combining membrane protein purification with surface-enhanced Raman spectroscopy (SERS) for noninvasive detection of nasopharyngeal carcinoma (NPC). A rapid and convenient protein purification method based on cellulose acetate membrane was developed. A total of 659 high-quality SERS spectra were acquired from purified proteins extracted from the saliva samples of 170 patients with pathologically confirmed NPC and 71 healthy volunteers. Spectral analysis of those saliva protein SERS spectra revealed specific changes in some biochemical compositions, which were possibly associated with NPC transformation. Furthermore, principal component analysis combined with linear discriminant analysis (PCA-LDA) was utilized to analyze and classify the saliva protein SERS spectra from NPC and healthy subjects. Diagnostic sensitivity of 70.7%, specificity of 70.3%, and diagnostic accuracy of 70.5% could be achieved by PCA-LDA for NPC identification. These results show that this assay based on saliva protein SERS analysis holds promising potential for developing a rapid, noninvasive, and convenient clinical tool for NPC screening.

Establishment of ultrasensitive PCR assay targeting cell-freeEBVDNA for early detection of nasopharyngeal carcinoma

In Vietnam, nasopharyngeal carcinoma (NPC) is the eighth most common cause of death from cancer. Cell-free Epstein Barr virus DNA (cf-EBV DNA) was reported to be present in almost all NPC patients. However, currently available assays in Vietnam can detect cf-EBV DNA in only 67.6% of NPC patients, thus leaving 32.4% of cancer cases undetected. Therefore, in this study, we aim to develop a highly sensitive quantitative PCR (qPCR) assay that measures the load of cf-EBV DNA for the purpose of early detection of NPC, and then evaluate the sensitivity and the specificity of the developed qPCR assay on the clinical samples. The major methods used in this study include primer/TaqMan probe design, cf-DNA extraction, optimization of qPCR assay and statistical analysis. Using an international standard panel from the Chinese University of HongKong, the linear range of developed qPCR assay is from 50-150,000 copies/ml (R2 = 0.99613) and the detection limit has been shown to be 25 copies/ml. The developed assay could detect cf-EBV DNA with a sensitivity of 96.9% (31/32 NPC patients) and cf-EBV DNA has not been detected in 103 out of 105 healthy controls, which corresponds to a specificity of 98%. Consequently, the performance of the optimal assay has achieved remarkably high sensitivity and specificity. Moreover, the detection limit of our optimal qPCR assay is 25 copies/ml of plasma, which is at least ten times better than other assays tested in recent studies in Vietnam. This developed qPCR assay will also form the basis for further studies in Vietnam and will open many new applications in management of NPC.