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Zhang G.,University of Hong Kong | Zong J.,Fujian Medical University | Lin S.,Fujian Medical University | Verhoeven R.J.A.,University of Hong Kong | And 8 more authors.
International Journal of Cancer | Year: 2015

More than 75% of nasopharyngeal carcinoma (NPC) patients have already developed local or regional spread at diagnosis, which hampers effective treatment and results in a poor prognosis. It is essential to characterize more sensitive and specific biomarkers for screening of high risk individuals and assessment of NPC treatment effectiveness. NPC is an Epstein-Barr virus (EBV) associated tumor in which only a few viral proteins but more than 20 BamHI A rightward transcripts (BART) microRNAs are detected, at abundant levels. We hypothesized that these BART microRNAs may be novel biomarkers for NPC. Systematic analysis of EBV BART microRNA expression profiles in EBV latently infected Mutu I and Mutu III cell lines, EBV-harboring NPC and noncancerous NP cells found that miR-BART3, miR-BART7 and miR-BART13 microRNAs are highly expressed and regularly secreted into the extracellular environment of NPC cells. These BART microRNAs were evaluated for used as potential NPC biomarkers. Analysis of plasma specimens obtained from NPC patients (n=89), and healthy (n=28) and non-NPC tumor patient controls (n=18) found levels of both miR-BART7 and miR-BART13, but not miR-BART3, to be distinctly presence among NPC patients, with elevated levels being particularly apparent among patients with advanced disease. Receiver operating characteristic curve analysis combining miR-BART7 and miR-BART13 levels produces a 90% predictive value for the presence of NPC. Analysis of 41 NPC patients before and after radiotherapy showed that miR-BART7 and miRBART13, but not miR-BART3, were diminished after treatment. These results indicate that EBV microRNAs, miR-BART7 and miRBART13, may constitute useful new serological biomarkers for diagnosis of NPC and prediction of treatment efficacy. © 2014 UICC.

Ji M.-F.,Cancer Research Institute of Zhongshan City | Cheng W.-M.,Cancer Research Institute of Zhongshan City | Yu B.-H.,Cancer Research Institute of Zhongshan City | Wu B.-H.,Cancer Research Institute of Zhongshan City | And 5 more authors.
Chinese Journal of Cancer Prevention and Treatment | Year: 2012

OBJECTIVE: To evaluate the cost effective of the new screening program for nasopharyngeal carcinoma (NPC) patients. METHODS: A new screening program was used in Zhongshan City with a high incidence for NPC. The effect was measured by using the cancer detection rate, early diagnosis rate, the cost per screening, the average early detection cost and the early detection cost index (EDCI). RESULTS: Totally 16 712 adults were recruited to the study with informed consent and 25 NPC cases were detected. The cancer detection rate was 149.59 per 100 000.The rate of early detection was 76.0% and these patient could be completely cured. The cost per screening was ¥41.56, and the detection cost was ¥27 779.82. The early detection cost was ¥36 552.40 and EDCI was 1.71 with the country GDP and 0.65 with the Zhongshan City GDP. CONCLUSION: Although the screening cost for NPC is higher than that for other cancers. The early diagnosis rate can be significantly improved which results an effective treatment.

Lian S.,Cancer Research Institute of Zhongshan City | Ji M.,City.com | Wu B.,Cancer Research Institute of Zhongshan City | Yu X.,Cancer Research Institute of Zhongshan City
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2015

OBJECTIVE: To investigate the relationship between changes in high-risk populations and screening detected nasopharyngeal carcinoma (NPC) during the three-year follow-up of high-risk and moderate-risk groups at initial EB virus serology screening.METHODS: We tested EB virus VCA-IgA and EBNA1-IgA antibody to identify the probability of suffering from NPC of the crowd. The high-risk and moderate-risk groups at initial screening in one county during 2009 to 2010 were followed-up once a year with EB virus serology testing. All the high-risk people during initial screening and follow-up were conducted with nasopharyngeal fiber endoscopy. Through the follow-up of three years, we analyzed changes in the number of high-risk group, detection rate of NPC in high-risk group, and tumor staging. Firstly detected NPC by screening was defined as screening group, and detected by following-up was defined as following-up group.RESULTS: A total of 404 participants were at high-risk and 1 041 participants were at moderate-risk group, 1 445 persons were in the group. All 404 persons were at high-risk at initial screening, the number of high-risk people during follow-up decreased from 371 to 187, 853 people of the all high-risk group were conducted with nasopharyngeal fiber endoscopy, and 38 cases of NPC were detected. NPC detection rate of high-risk group was 6.2% (25/404), 3.2% (12/371), 0.5% (1/188) and 0 (0/187) during the initial screening and three years follow-up respectively. The cumulative incidence of NPC in the high-risk and moderate-risk group were 7.7% (31/404) ,0.8% (8/1 041) . The early diagnosis rate of NPC in screening group and following-up group was 80% (20/25)and 11/13, respectively. With the primary tumor, the rate of T1 in screening group was higher than following-up group (80% to 38%, 20/25 to 5/13; P = 0.028). However, compared with following-up group, the rate of regional lymph node metastasis in screening group was higher (19/25 to 5/13; P = 0.035 ).CONCLUSION: Along with the high detection rate of early staging NPC in screening group and following-up group, the detection of NPC in high risk people is mainly at initial screening and the first year following-up and NPC detection rate thereafter is dropping significantly.

Ji M.-F.,Cancer Research Institute of Zhongshan City | Huang Q.-H.,Sihui Cancer Institute | Yu X.,Cancer Research Institute of Zhongshan City | Liu Z.,Karolinska Institutet | And 12 more authors.
Cancer | Year: 2014

BACKGROUND The utility of circulating Epstein-Barr Virus (EBV) DNA as a tumor marker for nasopharyngeal carcinoma (NPC) detection suggests that it might improve the diagnostic performance of anti-EBV antibody markers in NPC screening. In this study, the authors evaluated whether circulating EBV DNA load is capable of distinguishing NPC patients from high-risk individuals who have positive anti-EBV antibodies. METHODS In a population-based NPC screening trial in Sihui City and Zhongshan City, Guangdong Province, China, the authors previously identified 862 high-risk participants with 2 screening markers, immunoglobulin A (IgA) antibodies to EBV capsid antigen (VCA/IgA) and nuclear antigen-1 (EBNA1/IgA). In the current study, real-time polymerase chain reaction was used to measure the baseline plasma EBV DNA load among 825 participants (97%). Follow-up was extended to the end of 2011 to evaluate the diagnostic and predictive values of plasma EBV DNA load. RESULTS By using 0 copies/mL as the cutoff value, plasma EBV DNA had a sensitivity of 86.8% (33 of 38 patients) for NPC detected within the first year of follow-up, yielding a positive predictive value of 30% (33 of 110 participants) and a negative predictive value of 99.3% (696 of 701 participants). The patients who had early stage NPC had lower sensitivity (81.5%; 22 of 27 patients) than those who had advanced NPC (100%; 11 of 11 patients). For the 14 patients who had NPC detected after 1 year of follow-up, only 50% (7 of 14 patients) tested positive for EBV DNA at baseline. CONCLUSIONS The plasma EBV DNA load may improve the accuracy of diagnosing NPC in high-risk individuals, but it appears to have limited value in screening patients who have early stage NPC and predicting NPC development. Cancer 2014;120:1353-1360. © 2014 American Cancer Society. This study is the first to prospectively evaluate whether plasma Epstein-Barr virus (EBV) DNA load may serve as a complementary screening tool to distinguish nasopharyngeal carcinoma (NPC) patients from the individuals who are positive for anti-EBV antibodies in a population-based NPC screening trial in endemic areas. The results provide high-grade evidence that EBV DNA could be useful in clinical diagnosis of NPC but has limited value in screening for early stage NPC or predicting NPC development. © 2013 American Cancer Society.

Ji M.-F.,Cancer Research Institute of Zhongshan City | Yu Y.-L.,Cancer Research Institute of Zhongshan City | Cheng W.-M.,Cancer Research Institute of Zhongshan City | Zong Y.-S.,Sun Yat Sen University | And 3 more authors.
Chinese Journal of Cancer | Year: 2011

In a prospective study, 42 048 adults residing in Zhongshan City, Guangdong, China, were followed for 16 years, and 171 of them developed nasopharyngeal carcinoma (NPC). Although Epstein-Barr virus (EBV) antibody levels of the cohort fluctuated, the antibody levels of 93% of the patients with NPC were raised and maintained at high levels for up to 10 years prior to diagnosis. This suggests that the serologic window affords an opportunity to monitor tumor progression during the preclinical stage of NPC development, facilitating early NPC detection. We reviewed the clinical records of the 171 patients with NPC in the prospective study to assess the efficacy of early NPC detection by serologic screening and clinical examination. Of the 171 patients, 51 had Stage I tumor (44 were among the 73 patients detected by clinical examination and 7 were among the 98 patients presented to outpatient department). Initial serologic screening predicted 58 (95.1%) of the 61 patients detected within 2 years. The risk of the screened population (58/3093) raised 13 times relative to cohort (61/42 048) during this period. Clinical examination detected all the 58 predicted cases, and 35 (60.3%) of which were diagnosed with Stage I tumor. The serologic prediction rate fell to 33.6% (37/110) 2 to 16 years after screening. The proportion of cases detected by clinical examination fell to 40.5% (15/37). The proportion of Stage I tumors among the cases detected by clinical examination during both periods remained at about 60%. We concluded that early detection of NPC can be accomplished by repeated serologic screening to maintain high prediction rates and by promptly examining screened subjects to detect tumors before the symptoms develop.

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