Development and validation of the health belief model questionnaire to promote smoking cessation for nasopharyngeal cancer prevention: a cross-sectional study.

OBJECTIVE: Lifestyle-induced nasopharyngeal carcinoma is a serious but preventable risk factor. This study serves to develop and validate a questionnaire that aims to predict the health behavioural intention on smoking cessation in Sarawak, Malaysia using the Health Belief Model (HBM). DESIGN: A cross-sectional study. SETTING: Urban and suburban areas in Sarawak, Malaysia. PARTICIPANTS: The preliminary items of the instrument were developed after extensive literature review. The instrument was translated into the Malay language using the forward-backwards method before commencing with the content validity by a panel of 10 experts. Face validity was done both quantitatively and qualitatively by 10 smokers. The construct validity of the instrument was evaluated through exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). A total of 100 smokers participated in phase 1 for EFA, while 171 smokers participated in phase 2 for CFA. Internal consistency was measured using Cronbach's alpha coefficients to evaluate the reliability. RESULTS: In the exploratory stage, the factor loading of each item remained within the acceptable threshold. The final revised CFA yielded appropriate fit of the seven-factor model with the following model fit indices: χ2=641.705; df=500; p<0.001; comparative fit index=0.953; Tucker-Lewis Index=0.948; root mean square error of approximation=0.041. Satisfactory convergent validity and divergent validity were shown, with the exception of one pairwise construct. The internal reliability of these scales was above the desirable threshold, with Cronbach's alpha coefficients ranging from 0.705 to 0.864 and 0.838 to 0.889 in phases 1 and 2, respectively. CONCLUSIONS: The study substantiated the instrument to be valid and reliable for predicting smokers' health behavioural intention to reduce cancer risk. The instrument is made up of 34 items, categorised into two sections, six HBM constructs and health behavioural intention. The instrument can be utilised for other smoking cessation-related cancers in different at-risk populations.

Survey on determinants of intention to reduce nasopharyngeal cancer risk: an application of the theory of planned behavior.

BACKGROUND: To have better prognostic outcomes and minimize deaths due to nasopharyngeal cancer, it is vital to understand factors that motivate the public to undertake cancer preventive measures. The study investigated determinants of intention to adopt measures to reduce nasopharyngeal cancer risk using the Theory of Planned Behavior. METHOD: A cross-sectional survey was conducted on Malaysians (n = 515) using a questionnaire on attitudes, subjective norm, perceived behavioral control, knowledge of nasopharyngeal cancer, past nasopharyngeal cancer preventive behavior, and intention to adopt preventive measures. The attitudes construct encompassed perceptions of susceptibility, severity, benefits and barriers. Hierarchical regression of mediation effect under structural equation model approach was used to test the theory. The model was re-estimated using the two-stage least square approach by instrumental approach. Next the Maximum Likelihood Estimation-Structural Equation Modeling was conducted to gauge the instrumentation and check the robustness of the model's simultaneity. RESULTS: The respondents had moderate knowledge of nasopharyngeal cancer, and reported high levels of perceived risk, perceived severity and perceived behavioral control. The respondents were under little social pressure (subjective norm) to perform nasopharyngeal cancer preventive actions, marginally believed in the benefits of medical tests and reported few barriers. The Partial Least Squares-Structural Equation Modeling results show that the relationship between intention and four independent variables were significant (perceived behavioral control, perceived risk, perceived severity, marital status) at p < .05. Tests of Two-stage Least Square Approach and Maximum Likelihood Estimation-Structural Equation Modeling confirm the four key factors in determining the intention to reduce nasopharyngeal cancer risk. The variance explained by these factors is 33.01 and 32.73% using Two-stage Least Square Approach and Maximum Likelihood Estimation-Structural Equation Modeling respectively. Intention to undertake nasopharyngeal cancer risk-reducing behavior has no significant relationship with subjective norm, attitudes (perceived benefits and barriers to screening), knowledge of nasopharyngeal cancer and past behavior in enacting nasopharyngeal cancer preventive measures. The only demographic variable that affects intention is marital status. Gender, age, race, religion, education level, and income are not significantly associated with intention. CONCLUSIONS: In contexts where knowledge of nasopharyngeal cancer is moderate, the factors associated with the intention to reduce risk are perceived risk and severity, perceived behavioral control, and marital status.

Supplemental folic acid and/or multivitamins in pregnancy is associated with a decreased risk of childhood and adolescent nasopharyngeal carcinoma.

The aim of this study was to evaluate the association between prenatal and neonatal period exposures and the risk of childhood and adolescent nasopharyngeal carcinoma (NPC). From January 2009 to January 2016, a total of 46 patients with childhood and adolescent NPC (i.e., less than 18 years of age) who were treated at Sun Yat-sen University Cancer Center were screened as cases, and a total of 45 cancer-free patients who were treated at Sun Yat-sen University Zhongshan Ophthalmic Center were selected as controls. The association between maternal exposures during pregnancy and obstetric variables and the risk of childhood and adolescent NPC was evaluated using logistic regression analysis. Univariate analysis revealed that compared to children and adolescents without a family history of cancer, those with a family history of cancer had a significantly higher risk of childhood and adolescent NPC [odds ratios (OR) = 3.15, 95% confidence interval (CI) = 1.02-9.75, P = 0.046], and the maternal use of folic acid and/or multivitamins during pregnancy was associated with a reduced risk of childhood and adolescent NPC in the offspring (OR = 0.07, 95% CI = 0.02-0.25, P < 0.001). After multivariate analysis, only the maternal use of folic acid and/or multivitamins during pregnancy remained statistically significant. These findings suggest that maternal consumption of folic acid and/or multivitamins during pregnancy is associated with a decreased risk of childhood and adolescent NPC in the offspring.

Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-181a retards nasopharyngeal carcinoma development by mediating KDM5C.

OBJECTIVE: It has been studied that mesenchymal stem cells (MSCs)-derived exosomes could suppress tumor growth in nasopharyngeal carcinoma (NPC) and microRNA-181a (miR-181a) could mediate drug resistance in NPC. Focused on this work, the mechanism of human umbilical cord MSCs (hUC-MSCs)-derived exosomal miR-181a was explored in NPC cell progression. METHODS: NPC tissues and normal tissues were obtained from patients, and miR-181a and KDM5C expression was examined. hUC-MSCs-derived exosomes were extracted, identified and co-cultured with NPC cells (C666-1 and SUNE1). C666-1 cell progression in vitro and/or tumor growth in vivo were examined after incubation with exosomes, miR-181a or lysine-specific demethylase 5C (KDM5C). miR-181a and KDM5C expression were examined in NPC. RESULTS: miR-181a expression was reduced while KDM5C expression was elevated in NPC. hUC-MSCs-derived exosomes restrained NPC cell growth in vivo and in vitro. Depleting or restoring exosomal miR-181a promoted or delayed NPC cell progression. KDM5C silencing suppressed NPC cell progression. CONCLUSION: This study concluded that hUC-MSCs-derived exosomal miR-181a retards NPC development via negatively modulating KDM5C, serving as a candidate reference for the therapy of NPC.

The Association between Tea Consumption and Nasopharyngeal Cancer: A Systematic Review and Meta-Analysis

Heated debates have been on-going about tea consumption and the incidence of cancer, especially in head and neck cancer types. This study aimed to review the association between tea consumption habits and nasopharyngeal cancer (NPC). Methods: This review was carried out in accordance with the PRISMA-P protocol. Literature search for journal articles that published studies on the relationship between tea consumption and NPC was performed via databases, such as Elsevier, PubMed, Science Direct, Springer Link, Google, and Google Scholar, for 10 years from 2008 to 2018. Relevant studies were obtained by applying the pre-determined keywords, such as nasopharyngeal cancer, tea consumption and NPC, risk factors of NPC and benefits of tea consumption. Results: A total of 126 articles was retrieved. These articles were subjected to eligibility assessment. Six articles remained after applying the inclusion criteria. Results suggest that habitual tea consumption reduces NPC. Tea consumption significantly reduces NPC with all the studies having a p-value ≤0.05. Meta-analysis showed statistical association between tea consumption and NPC risk with OR=0.865 at 95% CI (0.806-0.929). Conclusion: This study suggests that habitual tea consumption could be associated with prevention of NPC development. Additional studies are needed to further understand the molecular role of bioactive compound and potential health benefit of tea consumption in NPC prevention.

The promise of a prophylactic Epstein-Barr virus vaccine.

The worldwide burden of disease due to Epstein-Barr virus (EBV) infection is enormous. Diseases include endemic Burkitt lymphoma, infectious mononucleosis, cancers after transplantation, Hodgkin lymphoma, and nasopharyngeal carcinoma. A prophylactic EBV vaccine has the potential to significantly reduce the incidence and/or the severity of all these diseases. Infectious mononucleosis can be nasty and prolonged with a median duration of 17 days. Patients, especially children, undergoing bone marrow or solid organ transplantation may develop post-transplant lymphoproliferative disorder (PTLD). Preventing or modifying primary EBV infection could reduce the incidence PTLD, and also certain lymphomas and nasopharyngeal carcinoma. EBV is a major environmental risk factor for multiple sclerosis (MS). Contracting EBV is essential to getting MS, and having a childhood case of infectious mononucleosis increases that risk. Vaccinating against EBV could be vaccinating against MS.

Prophylactic and therapeutic strategies for Epstein-Barr virus-associated diseases: emerging strategies for clinical development.

INTRODUCTION: Epstein-Barr virus (EBV) infects more than 95% of the world's population and is associated with infectious mononucleosis as well as a number of cancers in various geographical locations. Despite its significant health burden, no licenced prophylactic or therapeutic vaccines are available. Areas covered: Over the last two decades, our understanding of the role of EBV infection in the pathogenesis and immune regulation of EBV-associated diseases has provided new lines of research to conceptualize various novel prophylactic and therapeutic approaches to control EBV-associated disease. In this review, we evaluate the prophylactic and therapeutic vaccine approaches against EBV and various immunotherapeutic strategies against a number of EBV-associated malignancies. This review also describes the existing and future prospects of improved EBV-targeted therapeutic strategies. Expert opinion: It is anticipated that these emerging strategies will provide answers for the major challenges in EBV vaccine development and help improve the efficacy of novel therapeutic strategies.

Metformin and risk of developing nasopharyngeal cancer in patients with type 2 diabetes mellitus.

BACKGROUND: Metformin has anticancer effects, but whether it can reduce the risk of nasopharyngeal cancer (NPC) is not known. METHODS: A total of 15,486 ever-users and 15,486 never-users of metformin matched by propensity score were enrolled from among patients with new-onset type 2 diabetes mellitus diagnosed during the period 1999-2005 and who were found in the reimbursement database of Taiwan's National Health Insurance. The patients were followed until December 31, 2011. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity scores. RESULTS: NPC incidence was 33.41 and 106.04 per 100,000 person-years in ever-users and never-users, respectively. The overall hazard ratio (95% confidence interval) of 0.312 (0.197-0.494) favored a significantly lower risk among metformin ever-users than in never-users. Hazard ratios comparing the first (<26.03 months), second (26.03-58.03 months) and third (>58.03 months) tertiles of cumulative duration of metformin use to never-users were 0.690 (0.389-1.224), 0.187 (0.076-0.463) and 0.168 (0.068-0.415), respectively. A significantly lower risk of NPC was consistently observed among metformin users in subgroup analyses of age (<50 years and ≥50 years), sex (men and women), and patients with or without nephropathy, liver diseases or diseases of the esophagus, stomach, and duodenum, respectively. CONCLUSIONS: Metformin use is associated with a significantly lower risk of NPC.

Rubus idaeus Inhibits Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Suppression of MMP-2 through Modulation of the ERK1/2 Pathway.

Nasopharyngeal carcinoma (NPC) is characterized by a high incidence of metastasis in the neck lymph nodes, resulting in a poor prognosis and posing challenges for treatment. In this study, we investigated the in vitro antimetastatic properties of Rubus idaeus extract (RIE) on human nasopharyngeal carcinoma cells. HONE-1, NPC-39 and NPC-BM cells were subjected to RIE treatment, and effects on the migration and invasion of tumor cells were analyzed. The results showed that RIE suppressed the migration and invasion of NPC cells. Gelatin zymography assay, Western blotting and real-time PCR showed that matrix metalloproteinases-2 (MMP-2) enzyme activity, protein expression and mRNA levels were down-regulated by RIE treatment. To identify the signaling pathway, mitogen-activated protein kinase proteins were examined, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of RIE. In summary, our data showed that RIE inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by down-regulating the ERK1/2 signaling pathway, suggesting that Rubus idaeus may serve as chemotherapeutic and chemopreventive agent for NPC.

Beating 'Guangdong cancer': a review and update on nasopharyngeal cancer.

Once endemic in southern China, nasopharyngeal cancer is becoming less prevalent in Hong Kong. This is probably due to a better understanding of the risk factors associated with the disease, its genomic landscape, advances in radiotherapy technology, and development of effective systemic agents. More specifically, the close relationship between Epstein-Barr virus and nasopharyngeal cancer opens up the possibility of using Epstein-Barr virus DNA as a biomarker for early detection and monitoring of the disease. On the other hand, the looming genomic data for nasopharyngeal cancer aid in the development of powerful biomarkers and promising targeted therapy. Clinical use of a combination of radiotherapy and chemotherapy continues to increase, while the development of immunotherapy, such as checkpoint inhibitors, offers hope in improving treatment outcome.

MicroRNA-212 inhibits the metastasis of nasopharyngeal carcinoma by targeting SOX4.

MicroRNAs are important factors in the pathogenic processes of human types of cancers including nasopharyngeal carcinoma (NPC). In the present study, we confirmed that the microRNA-212 expression level was significantly decreased both in NPC tissues and NPC cell lines. Decreased expression of miR-212 was associated with advanced tumor-node-metastasis (TNM) stage and metastasis of NPC. Patients with a lower level of miR-212 had significantly decreased rates of overall and disease-free survival. Functional experiments showed that forced expression of miR-212 inhibited the migration and invasion of NPC cells while inhibition of miR-212 increased the migration and invasion of NPC cells. Furthermore, the results of luciferase assay, qRT-PCR and western blotting showed that SOX4 was the direct downstream target of miR-212 in NPC cells. In addition, we further confirmed that miR-212 exerted its inhibitory influence on the migration and invasion of NPC cells by targeting SOX4.

Designing an effective vaccine to prevent Epstein-Barr virus-associated diseases: challenges and opportunities.

INTRODUCTION: Epstein-Barr virus (EBV) is a ubiquitous herpesvirus associated with a number of clinical manifestations. Primary EBV infection in young adolescents often manifests as acute infectious mononucleosis and latent infection is associated with multiple lymphoid and epithelial cancers and autoimmune disorders, particularly multiple sclerosis. Areas covered: Over the last decade, our understanding of pathogenesis and immune regulation of EBV-associated diseases has provided an important platform for the development of novel vaccine formulations. In this review, we discuss developmental strategies for prophylactic and therapeutic EBV vaccines which have been assessed in preclinical and clinical settings. Expert commentary: Major roadblocks in EBV vaccine development include no precise understanding of the clinical correlates of protection, uncertainty about adjuvant selection and the unavailability of appropriate animal models. Recent development of new EBV vaccine formulations provides exciting opportunities for the formal clinical assessment of novel formulations.

Tumour-inducing viruses.

Virus infections are an important factor in the global burden of human cancer. The discovery and mode of action of human tumour viruses is briefly reviewed together with the promise of prevention through vaccination.

Diet Quality Scores and Risk of Nasopharyngeal Carcinoma in Chinese Adults: A Case-Control Study.

Many studies show that dietary factors may affect the risk of nasopharyngeal carcinoma (NPC). We examined the association between overall diet quality and NPC risk in a Chinese population. This case-control study included 600 NPC patients and 600 matched controls between 2009 and 2011 in Guangzhou, China. Habitual dietary intake and various covariates were assessed via face-to-face interviews. Diet quality scores were calculated according to the Healthy Eating Index-2005 (HEI-2005), the alternate Healthy Eating Index (aHEI), the Diet Quality Index-International (DQI-I), and the alternate Mediterranean Diet Score (aMed). After adjustment for various lifestyle and dietary factors, greater diet quality scores on the HEI-2005, aHEI, and DQI-I-but not on the aMed-showed a significant association with a lower risk of NPC (p-trends, <0.001-0.001). The odds ratios (95% confidence interval) comparing the extreme quartiles of the three significant scores were 0.47 (0.32-0.68) (HEI-2005), 0.48 (0.33-0.70) (aHEI), and 0.43 (0.30-0.62) (DQI-I). In gender-stratified analyses, the favorable association remained significant in men but not in women. We found that adherence to the predefined dietary patterns represented by the HEI-2005, aHEI, and DQI-I scales predicted a lower risk of NPC in adults from south China, especially in men.

Folate, vitamin B6, vitamin B12 and methionine intakes and risk for nasopharyngeal carcinoma in Chinese adults: a matched case-control study.

Many studies have suggested that folate-related one-carbon metabolism-related nutrients may play a role in certain cancer risks, but few studies have assessed their associations with the risk for nasopharyngeal carcinoma (NPC). In this study, we investigated the association between four folate-related one-carbon metabolism-related nutrients (folate, vitamin B6, vitamin B12 and methionine) and NPC risk in Chinese adults. A total of 600 patients newly diagnosed (within 3 months) with NPC were individually matched with 600 hospital-based controls by age, sex and household type (urban v. rural). Folate, vitamin B6, vitamin B12 and methionine intakes were measured using a validated seventy-eight-item FFQ. A higher dietary folate or vitamin B6 intake was associated with a lower NPC risk after adjusting for potential confounders. The adjusted OR of NPC for quartiles 2-4 (v. 1) were 0·66 (95% CI 0·48, 0·91), 0·52 (95% CI 0·37, 0·74) and 0·34 (95% CI 0·23, 0·50) (P(trend)<0·001) for folate and 0·72 (95% CI 0·52, 1·00), 0·55 (95% CI 0·39, 0·78) and 0·44 (95% CI 0·30, 0·63) (P(trend)<0·001) for vitamin B6. No significant association with NPC risk was observed for dietary vitamin B12 or methionine intake. The risk for NPC with dietary folate intake was more evident in the participants who were not exposed to toxic substances than in those who were exposed (P(interaction)=0·014). This study suggests that dietary folate and vitamin B6 may be protective for NPC in a high-risk population.

Mortality Characteristic and Prediction of Nasopharyngeal Carcinoma in China from 1991 to 2013.

BACKGROUND: To analyze the mortality distribution of nasopharyngeal carcinoma in China from 1991 to 2013, to predict the mortality in the ensuing five years, and to provide evidence for prevention and treatment of nasopharyngeal carcinoma. MATERIALS AND METHODS: Mortality data for Nasopharyngeal Carcinoma in China from 1991 to 2013 were used to describe its epidemiological characteristics, such as the change of the standardized mortality rate, sex and age differences, urban-rural differences. Trend-surface analysis was used to study the geographical distribution of the mortality. Curve estimation, time series, gray modeling, and joinpoint regression were used to predict the mortality for the ensuing five years in the future. RESULTS: In China, the standardized mortality rate of Nasopharyngeal Carcinoma increased with time from 1996, reaching the peak values of 1.45 /105 at the year of 2002, and decreased gradually afterwards. With males being 1.51 times higher than females, and the city had a higher rate than the rural during the past two decades. The mortality rate increased from age 40. Geographical analysis showed the mortality rate increased from middle to southern China. CONCLUSIONS: The standardized mortality rate of Nasopharyngeal Carcinoma is falling. The regional disease control for Nasopharyngeal Carcinoma should be focused on Guangdong province of China, and the key targets for prevention and treatment are rural men, especially after the age of 40. The mortality of Nasopharyngeal Carcinoma will decrease in the next five years.

Anticancer activity of recombinant Siva1 protein in human nasopharyngeal carcinoma cell line CNE-2.

AIMS: To clone and express Siva1 protein, and to investigate the role of Siva1 protein in proliferation, apoptosis, invasion, and migration of human nasopharyngeal carcinoma cell line CNE-2 in vitro and in vivo. METHODS: The PCR fragment of Siva1 from human nasopharyngeal carcinoma cell line CNE-2 were double digested with BamHI and SalI and then induced into the pQE30 vector double digested by the same enzymes. The pQE30 vector harboring Siva1 was introduced into M15 competent cells and then induced by isopropyl ß -D-1-thiogalactopyranoside (IPTG). The Siva1 fusion protein was identified by 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and then separated and purified by Ni-affinity chromatography. Subsequently, the effects of recombinant Siva1 protein on proliferation, apoptosis, invasion and migration were assayed in vitro and in vivo. RESULTS: The transformed cells expressed Siva1 fusion protein with a molecular weight of approximately 12 kDa. Cell counting kit-8 (CCK-8) assay showed that the Siva1 protein significantly inhibited the proliferation of the CNE-2 cells at a concentration of 10 µ mol/L. In addition, compared to the control, the Siva1 protein promoted the apoptosis of the cancer cells. And, the Siva1 protein greatly suppressed the invasion and migration of the cancer cells. In vivo, the Siva1 protein significantly inhibited the tumor growth of the tumor-bearing mice. Further, the Siva1 treatment markedly upregulated Bax, caspase-3, and downregulated Bcl-2 protein levels in the transplanted tumor tissue. CONCLUSIONS: The Siva1 protein has a significant anticancer activity on human nasopharyngeal carcinoma cell line CNE-2 including inhibiting proliferation, invasion, migration and promoting apoptosis of the cancer cells.

MR imaging prediction of local control of nasopharyngeal carcinoma treated with radiation therapy and chemotherapy.

OBJECTIVE: To retrospectively evaluate the association of MRI findings with local control of nasopharyngeal carcinoma (NPC) treated with radiation therapy and chemotherapy (chemoradiotherapy). METHODS: Pre-treatment MRIs of 101 patients (78 males and 23 females, 23-79 years of age) who had NPC treated with chemoradiotherapy were retrospectively reviewed to evaluate tumour involvement of nasopharyngeal anatomic subsites, tumour volume and MRI appearance. Local control rates were evaluated with respect to these MRI findings. RESULTS: Univariate analysis (using the Kaplan-Meier method) showed that invasion of the skull base as determined by MRI was a significant predictor of local control. In terms of clinical characteristics, T stage and pathological subtype were significant predictors of local control. Multivariate analysis (Cox regression model) of the radiologic findings and clinical characteristics revealed that invasion of the skull base (p = 0.003) and pathological subtype (p < 0.001) were independent prognostic factors for local control. CONCLUSION: Invasion of the skull base as determined by MRI predicts the likelihood of local failure and may be helpful in identifying a subset of patients with tumours at risk of local recurrence within 3 years after primary chemoradiotherapy. ADVANCES IN KNOWLEDGE: It has now become common practice to use MRI for pre-treatment evaluation of patients with NPC. The potential role for MRI findings in predicting local control and prognosis in patients with NPC has implications for treatment planning.

Fiber intake and risk of nasopharyngeal carcinoma: a case-control study.

Some studies examined the inverse relation between nasopharyngeal carcinoma (NPC) risk and dietary fibers in endemic populations. By means of a hospital-based case-control study, we verified whether this association was also present in Italy in connection with various types of dietary fibers. Cases were 198 patients with incident, histologically confirmed, NPC admitted to major teaching and general hospitals during 1992-2008. Controls were 594 patients admitted for acute, nonneoplastic conditions to the same hospital network of cases. Information was elicited using a validated food frequency questionnaire including 78 foods, food groups, or dishes. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were estimated for quartiles of intake of different types of fiber after allowance for energy intake and other potential confounding factors. Total fiber intake was inversely related to risk of NPC (OR = 0.58 for the highest vs. the lowest quartile of intake; 95% CI: 0.34-0.96). We found an inverse association for total soluble (OR = 0.58; 95% CI: 0.35-0.96) and total insoluble fiber (OR = 0.56; 95% CI: 0.33-0.95), in particular cellulose (OR = 0.57; 95% CI: 0.33-0.96), and lignin (OR = 0.51; 95% CI: 0.31-0.85). In conclusion, this study suggests that dietary intake of soluble and insoluble fibers is inversely related to NPC risk in a nonendemic southern population.