Kinetics of EBV antibody-based NPC risk scores in Taiwan NPC multiplex families.

Nasopharyngeal carcinoma (NPC) risk prediction models based on Epstein-Barr virus (EBV)-antibody testing have shown potential for screening of NPC; however, the long-term stability is unclear. Here, we investigated the kinetics of two EBV-antibody NPC risk scores within the Taiwan NPC Multiplex Family Study. Among 545 participants with multiple blood samples, we evaluated the stability of a 2-marker enzyme-linked immunosorbent assay score and 13-marker multiplex serology score using the intra-class correlation coefficient (ICC) by fitting a linear mixed model that accounted for the clustering effect of multiple measurements per subject and age. We also estimated the clustering of positive tests using Fleiss's kappa statistic. Over an average 20-year follow-up, the 2-marker score showed high stability over time, whereas the 13-marker score was more variable (p < .05). Case-control status is associated with the kinetics of the antibody response, with higher ICCs among cases. Positive tests were more likely to cluster within the same individual for the 2-marker score than the 13-marker score (p < .05). The 2-marker score had an increase in specificity from ~90% for single measurement to ~96% with repeat testing. The 13-marker score had a specificity of ~73% for a single measurement that increased to ~92% with repeat testing. Among individuals who developed NPC, none experienced score reversion. Our findings suggest that repeated testing could improve the specificity of NPC screening in high-risk NPC multiplex families. Further studies are required to determine the impact on sensitivity, establish optimal screening intervals, and generalize these findings to general population settings in high-risk regions.

A Novel Prediction Model Based on Quantitative Texture Analysis of Sonographic Images for Malignant Major Salivary Glandular Tumors.

Background: The aim of this study was to compare multiple objective ultrasound (US) texture features and develop an objective predictive model for predicting malignant major salivary glandular tumors. Methods: From August 2007 to May 2018, 144 adult patients who had major salivary gland tumors and subsequently underwent surgery were recruited for this study. Representative brightness mode US pictures were selected for texture analysis and used to develop a prediction model. Results: We found that the grayscale intensity and standard deviation of the intensity were significantly different between malignant and pleomorphic adenomas. The contrast, inverse difference (INV) movement, entropy, dissimilarity, and INV also differed significantly between benign and malignant tumors. We used stepwise selection of predictors to develop an objective predictive model, as follows: Score = 1.138 × Age - 1.814 × Intensity + 1.416 × Entropy + 1.714 × Contrast. With an optimal cutoff of 0.58, the diagnostic performance of this model had a sensitivity, specificity, overall accuracy, and area under the curve of 83% (95% confidence interval [CI]: 74%-92%), 74% (65%-84%), 78% (72%-85%), and 0.86 (0.80-0.92), respectively. Conclusion: We have developed a novel computerized diagnostic model based on objective US features to predict malignant major salivary gland tumor. Further improving the computer-aided diagnosis model might change the US examination for major salivary gland tumors in the future.

Trends and sex-specific incidence of upper urinary tract cancer in Taiwan: A birth cohort study.

BACKGROUND: Taiwan has one of the highest incidences of upper tract urothelial cancer (UTUC) worldwide, especially in women; however, no nationwide, long-term follow-up study has evaluated this. METHODS: We investigated the incidence of UTUC in Taiwan using data from the national population-based Taiwan Cancer Registry database (1985-2019). We divided the birth cohort into nine 5-year age groups and calculated the age-specific incidence for these groups according to the corresponding birth years. RESULTS: The average annual percent change in the incidence of renal pelvis cancer from 1985 to 2019 showed sex-specific differences, with 3.5% and 5.3% increases in the incidences in men and women, respectively. The age-specific incidence rate for renal pelvis cancer among women showed a gradual increase in the group with older women as well as an increase over time in each age group. The results of a birth cohort analysis revealed that younger cohorts had higher incidence rates of renal pelvis cancer than older cohorts did. CONCLUSION: We demonstrated that the incidence of UTUC is unusually high among older Taiwanese women and that younger cohorts have a high risk of UTUC than older cohorts.

Performance and Operational Feasibility of Epstein-Barr Virus-Based Screening for Detection of Nasopharyngeal Carcinoma: Direct Comparison of Two Alternative Approaches.

PURPOSE: Two Epstein-Barr virus (EBV)-based testing approaches have shown promise for early detection of nasopharyngeal carcinoma (NPC). Neither has been independently validated nor their performance compared. We compared their diagnostic performance in an independent population. METHODS: We tested blood samples from 819 incident Taiwanese NPC cases (213 early-stage, American Joint Committee on Cancer version 7 stages I and II) diagnosed from 2010 to 2014 and from 1,768 controls from the same region, frequency matched to cases on age and sex. We compared an EBV antibody score using immunoglobulin A antibodies measured by enzyme-linked immunosorbent assay (EBV antibody score) and plasma EBV DNA load measured by real-time PCR followed by next-generation sequencing (NGS) among EBV DNA-positive individuals (EBV DNA algorithm). RESULTS: EBV antibodies and DNA load were measured for 2,522 (802 cases; 1,720 controls) and 2,542 (797 cases; 1,745 controls) individuals, respectively. Of the 898 individuals positive for plasma EBV DNA and therefore eligible for NGS, we selected 442 (49%) for NGS testing. The EBV antibody score had a sensitivity of 88.4% (95% CI, 86.1 to 90.6) and a specificity of 94.9% (95% CI, 93.8 to 96.0) for NPC. The EBV DNA algorithm yielded significantly higher sensitivity (93.2%; 95% CI, 91.3 to 94.9; P = 1.33 × 10-4) and specificity (98.1%; 95% CI, 97.3 to 98.8; P = 3.53 × 10-7). For early-stage NPC, the sensitivities were 87.1% (95% CI, 82.7 to 92.4) for the EBV antibody score and 87.0% (95% CI, 81.9 to 91.5) for the EBV DNA algorithm (P = .514). For regions with a NPC incidence of 20-100/100,000 person-years (eg, residents in southern China and Hong Kong), these two approaches yielded similar numbers needed to screen (EBV antibody score: 5,656-1,131; EBV DNA algorithm: 5,365-1,073); positive predictive values ranged from 0.4% to 1.7% and 1.0% to 4.7%, respectively. CONCLUSION: We demonstrated high sensitivity and specificity of EBV antibody and plasma EBV DNA for NPC detection, with slightly inferior performance of the EBV antibody score. Cost-effectiveness studies are needed to guide screening implementation.

Feature Reviews of the Molecular Mechanisms of Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is rare in most parts of the world but endemic in southern Asia. Here, we describe the molecular abnormalities in NPC and point out potential molecular mechanisms for future therapy. This article provides a brief up-to-date review focusing on the molecular pathways of NPC, which may improve our knowledge of this disease, and we also highlight some issues for further research. In brief, some heritable genes are related to NPC; therefore, people with a family history of NPC have an increased risk of this disease. Carcinogenic substances and Epstein-Barr virus (EBV) exposure both contribute to tumorigenesis through the accumulation of multiple genomic changes. In recent years, salted fish intake has decreased the impact on NPC, which implies that changing exposure to carcinogens can modify the risk of NPC. Eradication of cancer-associated viruses potentially eradicates cancer, and EBV vaccines might also prevent this disease in the future. Screening patients by using an EBV antibody is feasible in the high-risk group; plasma EBV DNA measurement could also be conducted for screening, prognosis, and monitoring of this disease. Understanding the molecular mechanisms of NPC can further provide novel information for health promotion, disease screening, and precision cancer treatment.

Development of a Duplex Serological Multiplex Assay for the Simultaneous Detection of Epstein-Barr Virus IgA and IgG Antibodies in Nasopharyngeal Carcinoma Patients.

Epstein-Barr virus (EBV) IgA and IgG antibodies in serum from nasopharyngeal carcinoma (NPC) patients are well-established markers for EBV-positive NPC. Luminex-based multiplex serology can analyze antibodies to multiple antigens simultaneously; however, the detection of both IgA and IgG antibodies requires separate measurements. Here we describe the development and validation of a novel duplex multiplex serology assay, which can analyze IgA and IgG antibodies against several antigens simultaneously. Secondary antibody/dye combinations, as well as serum dilution factors, were optimized, and 98 NPC cases matched to 142 controls from the Head and Neck 5000 study (HN5000) were assessed and compared to data previously generated in separate IgA and IgG multiplex assays. EBER in situ hybridization (EBER-ISH) data available for 41 tumors was used to calibrate antigen-specific cut-offs using receiver operating characteristic (ROC) analysis with a prespecified specificity of ≥90%. A directly R-Phycoerythrin-labeled IgG antibody in combination with a biotinylated IgA antibody and streptavidin-BV421 reporter conjugate was able to quantify both IgA and IgG antibodies in a duplex reaction in a 1:1000 serum dilution. The combined assessment of IgA and IgG antibodies in NPC cases and controls from the HN5000 study yielded similar sensitivities as the separate IgA and IgG multiplex assays (all > 90%), and the duplex serological multiplex assay was able to unequivocally define the EBV-positive NPC cases (AUC = 1). In conclusion, the simultaneous detection of IgA and IgG antibodies provides an alternative for the separate IgA/IgG antibody quantification and may present a promising approach for larger NPC screening studies in NPC endemic areas.

Incidence trends of oral cavity, oropharyngeal, hypopharyngeal and laryngeal cancers among males in Taiwan, 1980-2019: a population-based cancer registry study.

In a country with a high prevalence of cigarette smoking, betel chewing, and alcohol drinking, cancers of the oral cavity, nasopharynx, and larynx were the fourth, twelfth and seventeenth leading causes of cancer death, respectively, for men in 2020. We analyzed patients with head and neck cancer from 1980 to 2019 from the Taiwan Cancer Registration Database and discussed the annual average percent change, average percent change, age period, and birth cohort. Obvious period effects and birth effects are seen in oral, oropharyngeal, and hypopharyngeal cancer; however, the most significant period effect was seen between 1990 and 2009, which mainly reflects the consumption of betel nuts per capita. In addition, the period effect lessens after 2010 in oral cancer and hypopharyngeal cancers, while oropharyngeal cancers remain an obvious period effect, which results from the rising prevalence of HPV. Due to the high prevalence rate of betel quid chewing and cigarette smoking in the 1990s, the government executed several acts. As a result, the age-adjusted incidence rates of oral, oropharyngeal, and hypopharyngeal cancers have flattened since 2010, which can be explained by the declining cigarette smoking rate. The strict policy indeed shows an obvious effect on the head and neck cancer incidence rates, and we expect to see a further decline in the future.

Association of Dipeptidyl Peptidase-4 Inhibitors Use with Reduced Risk of Hepatocellular Carcinoma in Type 2 Diabetes Patients with Chronic HBV Infection.

Previous studies have indicated that HBV infection and T2DM are the factors that increase the risk of developing HCC. The experimental evidence has shown that antiglycemic agents may reduce the risk of HCC. However, the effect of dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) on the risk of HCC in T2DM patients with chronic HBV infection remains unclear. In this retrospective cohort study, we extracted patients with T2DM and chronic HBV infection from the National Health Insurance Research Database (NHIRD) in Taiwan. The cases were divided into DPP-4 inhibitors use and non-use groups, according to whether they received DPP-4 inhibitors treatment, and the risk of HCC was compared between the two groups. At the end of the follow-up, approximately 2.33% of DPP-4 inhibitors users had received an HCC diagnosis compared with 3.33% of non-DPP-4 inhibitors users (p < 0.0001). After multivariate adjustment, DPP-4 inhibitors users showed a significant reduction in HCC risk (adjusted hazard ratios (aHRs): 0.53; 95% confidence intervals (CIs): 0.44-0.65). In conclusion, this population-based retrospective cohort study indicated that, in T2DM patients with chronic HBV infection, the use of DPP-4 inhibitors significantly reduced the risk of developing HCC compared with non-DPP-4 inhibitors use.

Comparative Analysis of the Humoral Immune Response to the EBV Proteome across EBV-Related Malignancies.

BACKGROUND: Epstein-Barr virus (EBV) is linked to multiple cancers, including classical Hodgkin lymphoma (cHL), endemic Burkitt lymphoma (eBL), nasopharyngeal carcinoma (NPC), and extranodal natural killer/T-cell lymphoma (NKTCL). METHODS: Anti-EBV IgG and IgA antibody responses targeting 202 sequences from 86 EBV proteins were measured using the same EBV whole proteome array across four case-control studies investigating EBV-positive cHL, eBL, NPC, and NKTCL (407 cases/620 controls). We grouped EBV-targeted antibodies into pathways by immunoglobulin type (IgA and IgG) and life-cycle stage (latent, immediate early lytic, early lytic, late lytic, and glycoprotein) and evaluated their association with each cancer type. In an additional analysis, we focused on the subset of 46 individual antibodies representing the top candidates for each cancer and compared their associations across the four cancer types using multivariable linear regression models. RESULTS: IgA antibody responses targeting all EBV life-cycle stages were associated with NPC but limited to anti-early lytic stage for cHL. NPC and eBL were associated with IgG antibodies across the viral life cycle; cHL with antibodies in the early lytic, late lytic and glycoprotein stages; and NKTCL with antibodies in the latent, immediate early lytic and early lytic phases. EBNA3A, BBLF1, BDLF4, and BLRF2 IgG antibodies were associated with all cancer types. CONCLUSIONS: Our observed similarities and differences across four EBV-associated cancers may inform EBV-related oncogenesis. IMPACT: Understanding the comparative humoral immune response across EBV-related cancers may aid in identifying shared etiologic roles of EBV proteins and inform unique pathogenic processes for each cancer.

Recommendations for Epstein-Barr virus-based screening for nasopharyngeal cancer in high- and intermediate-risk regions.

A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)-based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program.

Screening and surveillance of esophageal cancer by magnifying endoscopy with narrow band imaging improves the survival of hypopharyngeal cancer patients.

Introduction: Patients with head and neck cancer may develop a second primary neoplasm (SPN) of the esophagus due to field cancerization. This study investigated the impacts of esophageal cancer screening using magnifying endoscopy with narrow-band imaging (ME-NBI) on the outcomes of hypopharyngeal cancer patients. Methods: Patients with hypopharyngeal cancer diagnosed from 2008 to 2021 in a tertiary hospital were reviewed retrospectively. Screening and surveillance using ME-NBI examination of the esophagus were divided into three patterns: (1) ME-NBI never performed or more than 6 months after diagnosis of index primary hypopharyngeal cancer, (2) ME-NBI within 6 months only, and (3) ME-NBI within 6 months and regular surveillance. Results: A total of 261 were reviewed and 21 (8%) patients were in stage I, 20 (8%) in stage II, 27 (10%) in stage III, 116 (44%) in stage IVA, 65 (25%) in stage IVB, and 12 (5%) in stage IVC. Sixty-seven (26%) patients had SPN (50 esophagus, 10 oral cavity, 3 oropharynx, 2 nasopharynx, 1 larynx and 1 lung). Among esophageal SPN, 35 (70%) and 15 (30%) patients developed synchronous and metachronous neoplasia, respectively. In multivariate Cox regression analysis, advanced stages III and IV (compared with stages I and II, HR: 1.86, 1.18-2.95, p=0.008), ME-NBI examination of the esophagus received within 6 months and regular surveillance (HR: 0.53, 0.36-0.78, p=0.001) were independent factors affecting the overall survival of patients with hypopharyngeal cancer. Discussion: Our findings demonstrated that screening and surveillance of esophageal SPN by ME-NBI improves the survival of patients with hypopharyngeal cancer.

Application of Real-time Submental Ultrasonography to Assess Swallowing.

Background: Speech and swallowing dysfunction are common problems in head-and-neck cancer (HNC) survivors. Ultrasound (US) is a good method to assess suprahyoid muscles and hyoid bone movement, and it can provide valuable information on swallowing. The aims of this study were to measure the biometry of the supraglottic muscles and hyoid bone movement during swallowing and elucidate the application of real-time US for assessing swallowing dysfunction. Methods: We collected data from HNC and thyroid cancer patients with dysphagia symptoms and healthy controls without a history of cancer or dysphagia symptoms for comparison. Real-time submental US was used to check the anterior belly of the digastric muscle, geniohyoid (GH) muscles, and hyoid bone movement during swallowing. Logistic regression analysis was used to explore significant US predictors of dysphagia. Based on the regression coefficients of independent variables, we established the nomogram prediction model for dysphagia. Results: There were significant differences in GH size at contraction, GH size increase percentage, GH length at rest, GH length increase percentage, anterior displacement of the hyoid bone and superior displacement of the hyoid bone between the cancer survivors with dysphagia and volunteers without dysphagia. In multivariate logistic analysis, after adjusting for sex and age, the proportion of GH length contraction <22% (odds ratio [OR]: 6.8 95% confidence interval [CI]: 1.1-42.6) and hyoid bone superior displacement <3.3 mm (OR: 10.7, 1.8-64.1) were associated with a higher risk of dysphagia (P < 0.05). Conclusion: We confirmed that GH muscle and hyoid bone movement are important for normal swallowing function. US is a good method to assess the suprahyoid muscles and hyoid bone movement, which could provide valuable information on swallowing.

Secular Trends in Incidence of Esophageal Cancer in Taiwan from 1985 to 2019: An Age-Period-Cohort Analysis.

In Taiwan, the age-standardized incidence of EC, especially esophageal squamous cell carcinoma (ESCC), has increased substantially during the past thirty years. We described the incidence trends of EC from 1985−2019 by an average annual percentage change (AAPC) and age-period-cohort model by using Taiwan Cancer Registry data. Age-period-cohort modeling was used to estimate the period and cohort effects of ESCC and esophageal adenocarcinoma (EAC). The Spearman's correlation coefficient was used to analyze the correlation between age-adjusted incidence rates of EC and the prevalence of risk factors from national surveys. The results showed the incidence rate of ESCC in men (AAPC = 4.2, 95% CI = 3.1−5.4, p < 0.001) increased prominently from 1985−1989 to 2015−2019 while that of EAC in men (AAPC = 1.2, 95% CI = 0.9−1.5, p < 0.001) and ESCC in women (AAPC = 1.7, 95% CI = 1.4−2.1, p < 0.001) increased to a lesser degree. Increased period effects were observed in ESCC in men, ESCC in women, and EAC in men. High correlations were found between the risk factors and the increased birth-cohort effects of ESCC (p < 0.05). To conclude, the incidence of ESCC in both sex and EAC in men increased with statistical significance in recent decades. The increased prevalence of risk factors from approximately 1970−1995 could explain the increased cohort effects of ESCC.

Risk of CVD Following Radiotherapy for Head and Neck Cancer: An Updated Systematic Review and Meta-Analysis.

Background: The relative risk for cerebrovascular disease (CVD) is increased in patients with head and neck cancer (HNC) treated with radiotherapy (RT). However, the current relative risk for CVD following RT has not been well clarified. The purpose of this study was to analyze the effect of RT and update the risk of CVD following RT in HNC patients through a systematic review and meta-analysis. Material and Methods: We conducted an online database search and systematic review of observational studies that reported on CVD and extracranial carotid stenosis in patients with HNC who had undergone RT. Articles published in Medline and PubMed from 1980 to 2021 were identified and collected. Results: Of the forty-seven articles identified from PubMed and forty-four articles identified from 3 systematic reviews, twenty-two studies were included. We found that neck RT was a significant risk factor for CVD (HR 3.97, 95% CI: 2.89-5.45). Patients with HNC treated by RT had an increased OR (7.36, 95% CI: 4.13-13.11) for CVD, and approximately 26% (95% CI: 22%-31%) of HNC patients treated with RT were at risk for CVD with more than 50% reduction in carotid diameter. Conclusion: The risk of CVD is increased in patients with HNC treated by RT, and recent improvements in RT techniques may have contributed to the decreased risk of CVD. These results suggest that regular follow-up and appropriate screening for CVD should be required for patients with HNC.

Rising incidence of HPV positive oropharyngeal cancer in Taiwan between 1999 and 2014 where betel nut chewing is common.

BACKGROUND: The incidence of human papillomavirus (HPV) positive oropharyngeal cancer (OPC) is rising but HPV negative OPC is decreasing in Western countries. In Taiwan, the incidence of HPV negative OPC is common but the incidence of HPV positive OPC remains unknown. The objective of this study is to estimate the incidence trend and the survival of HPV positive OPC in Taiwan. METHODS: Between 1999 and 2014, primary tumor tissues from 425 incident OPCs were obtained from 5 medical centers in Taiwan. 408 OPCs were evaluated by the EasyChip HPV genotyping (King-Car, I-Lan, Taiwan) and 369 OPCs by p16 staining. The clinical data were retrospectively obtained from the medical records. RESULTS: In our study, 29% of OPCs were HPV positive. The percentage of HPV positive OPC was stable from 1999 to 2014 (25% (1999-2002), 30% (2003-2006), 30% (2007-2010), 29% (2011-2014)). The estimated crude incidence rate of HPV positive OPC increased significantly from 0.62 (1999-2002), 1.06 (2003-2006), 1.52 (2007-2010) to 1.74 (2011-2014) per 100,000 person-year. The sensitivity and specificity of p16 staining for positive HPV infection were 92% and 91%, respectively. The 5-year overall survival rates for patients with HPV positive OPC and with HPV negative OPC were 67.8% and 49.0%, respectively (HR = 0.52 (0.35-0.76), p = 0.0005). Patients with HPV positive OPC but no betel nut/cigarette exposure had the best overall survival (5-year: 88.2%, p < 0.0001). Patients with HPV negative OPC and betel nut/cigarette exposure had the worst overall survival (5-year: 46.6%, p < 0.0001). Patients with HPV positive OPC but also with betel nut/cigarette exposure had poorer 5-year overall survival (48.3%, p < 0.01). CONCLUSION: The incidence of HPV positive OPC is increasing along with HPV negative OPC, which leads to stably low percentage of HPV positive OPC in Taiwan. HPV positive OPC may become an important head and neck cancer when the incidence of HPV negative OPC declines in the near future. P16 is a useful surrogate marker for HPV infection in OPC and a good prognostic indicator for treatment outcome of OPC. Patients with HPV positive OPC but no betel nut/cigarette exposure has an excellent prognosis. Betel nut/cigarette exposure significantly worsens the prognosis of HPV positive OPC.

Nutritional status at diagnosis is prognostic for pharyngeal cancer patients: a retrospective study.

BACKGROUND: Malnutrition in head and neck cancer (HNC) patients is associated with increased morbidity and mortality. Several nutrition indicators have been reported to be related to the prognosis of HNC. However, the prognostic effect of these multiple nutrition factors in HNC is not well elucidated. The aim of this study was to evaluate the prognostic effect of these factors, including the novel hemoglobin, albumin, lymphocyte, and platelet (HALP) score, for pharyngeal cancers. MATERIAL AND METHODS: From 2008 to 2019, a total of 319 pharyngeal cancer patients were recruited. We collected adult patients with a diagnosis of nasopharyngeal carcinoma, oropharyngeal carcinoma and hypopharyngeal carcinoma. Patients who completed definite staging workup and treatment were selected for analysis. We traced nutritional and hematological parameters, including body mass index (BMI), albumin, and complete blood count, for survival analysis. RESULTS: We found that multiple nutritional markers, including BMI, hemoglobin, albumin, prognostic nutritional index (PNI), nutritional risk index (NRI) and HALP score, were important predictors for pharyngeal cancers in univariate Cox regression analysis. In multivariate analysis, we found that the HALP score was still an independent factor (HR: 1.62, 1.13-2.32 for overall survival [OS]) after adjusting of gender, age, cancer site, clinical stage, and BMI. The PNI was the most important independent factor for OS (HR: 3.12, 2.18-4.47) and cancer-specific survival (HR: 2.88, 1.88-4.41) in multivariate analysis. CONCLUSION: We found that multiple nutrition markers, including BMI, hemoglobin, albumin, PNI, NRI and HALP score, are important predictors for pharyngeal cancers. This is the first report confirming the prognostic effect of the HALP score for HNCs. Nutritional status at diagnosis should be given more attention in pharyngeal cancer patients.

Identifying Epstein-Barr virus peptide sequences associated with differential IgG antibody response.

BACKGROUND: Epstein-Barr virus (EBV) infection contributes to cancers in a fraction of seropositive individuals, but much remains to be learned about variation in EBV-directed humoral immunity in cancer-free adults. METHODS: A protein microarray was used to probe serum from 175 Taiwanese and 141 Northern European adults for immunoglobulin G (IgG) antibody responses to 115 different peptide sequences, representing protein segments or protein variants, from 45 EBV proteins. It was posited that this antibody-based approach could identify EBV peptide sequences representing immunodominant regions relevant for B-cell immunity. RESULTS: Analyses of 45 EBV proteins with multiple protein segments or variants printed on the array identified eight EBV peptide sequences that appear to play a role in immunogenicity. This included: (1) three proteins with segments/regions associated with IgG reactivity (BALF5, LMP1, LMP2A); and (2) five proteins with sequence variants/amino acid changes associated with IgG reactivity (BDLF4, EBNA3A, EBNA3B, EBNA-LP, LF1). CONCLUSION: This examination of IgG antibody responses against 115 EBV peptide sequences in 316 cancer-free adults represents an important step toward identifying specific EBV protein sequences that play a role in generating B-cell immunity in humans.

A study to quantify surgical plume and survey the efficiency of different local exhaust ventilations.

This study aimed to compare the concentration of surgical smoke produced by different tissues and electric diathermy modes and to measure the effectiveness of various local exhaust ventilations. We compared the surgical plume concentration from different tissues and settings with a porcine tissue model. We also compared the efficiency of three local exhaust ventilations: (1) a desktop unit (Medtronic Rapid Vac), (2) a central evacuation system with ENT suction, and (3) a central evacuation system with a urethral catheter (PAHSCO Urethral Catheter). In the cutting setting, the skin tissue had a higher concentration of total suspended particulates (TPS), which were 1990 ± 2000 (mean ± SD, µg/m3), 6440 ± 3000 and 9800 ± 2300 at 15, 30 and 45 s, respectively (p < 0.05). In the coagulation setting, the adipose tissue had a higher concentration of TPS, which were 3330 ± 2600, 11,200 ± 5500 and 15,800 ± 7300, respectively (p < 0.05). We found that all three smoke extractors had more than 96% efficiency in clearing surgical smoke. With electric diathermy, skin tissue in the cutting model and adipose tissue in the coagulation mode will produce higher concentration of particles within surgical plumes. An electric surgical scalpel adapted with a urethral catheter is a simple and effective way to exhaust smoke in surgical operations.

Cancer patterns in nasopharyngeal carcinoma multiplex families over 15 years.

BACKGROUND: Genetic and environmental factors are important determinants of nasopharyngeal carcinoma (NPC). NPC is associated with Epstein-Barr virus (EBV) infection. Studies have reported familial aggregation of NPC, but evidence has been mixed for elevated rates of cancers other than NPC. METHODS: The authors reassessed their previous evaluation of familial aggregation of cancer in 348 high-risk Taiwanese multiplex families with 2 or more NPC cases enrolled between 1980 and 2003. Participants were linked to the Taiwan National Cancer Registry and National Death Registry to identify cancers. RESULTS: In all, 2590 individuals contributed 37,959 person-years over an average of 15 years of follow-up; 314 incident cancers were identified. The authors computed multiple primary standardized incidence ratios (MP-SIRs) to evaluate the overall risk and the risk of infection-associated, EBV-associated, and individual cancers. The overall MP-SIR was 1.24 (95% confidence interval [CI], 1.10-1.38). The exclusion of excess NPC risk led to an overall MP-SIR of 1.11 (95% CI, 0.98-1.25). Similarly, the risk of cancers associated with infectious agents was driven by the excess in NPC, and its exclusion led to an MP-SIR of 1.22 (95% CI, 0.99-1.48) for infection-associated cancers and to an MP-SIR of 1.18 (95% CI, 0.72-1.82) for EBV-associated cancers. The authors observed a significant excess of second cancers among NPC cases (oral cancer, mouth cancer, tongue cancer, gum cancer, nasal cavity cancer, bone cancer, and non-Hodgkin lymphoma). CONCLUSIONS: This reassessment of the largest NPC multiplex family study confirms the presence of NPC coaggregation within families in Taiwan but does not provide evidence for a broader familial syndrome involving NPC and other tumors. Among NPC cases, elevated rates of secondary cancers, mostly at the, head and neck and hematopoietic cancers suggest radiation treatment effects on subsequent cancer risk.

Smoking and nasopharyngeal cancer: individual data meta-analysis of six prospective studies on 334 935 men.

BACKGROUND: The role of smoking in nasopharyngeal carcinoma (NPC) remains uncertain, especially in endemic regions. We conducted an individual participant data (IPD) meta-analysis of prospective cohort studies to investigate the associations between smoking exposure and risk of NPC. METHODS: We obtained individual participant data of 334 935 male participants from six eligible population-based cohorts in NPC-endemic regions, including two each in Guangzhou and Taiwan, and one each in Hong Kong and Singapore. We used one- and two-stage approaches IPD meta-analysis and Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of NPC for smoking exposure adjusting for age and drinking status. RESULTS: During 2 961 315 person-years of follow-up, 399 NPC evens were ascertained. Risks of NPC were higher in ever versus never smokers (HRone-stage = 1.32, 95% CI = 1.07-1.63, P = 0.0088; HRtwo-stage = 1.27, 1.01-1.60, 0.04). These positive associations appeared to be stronger in ever smokers who consumed 16+ cigarettes/day (HRone-stage = 1.67, 95% CI = 1.29-2.16, P = 0.0001), and in those who started smoking at age younger than 16 (2.16, 1.33-3.50, 0.0103), with dose-response relationships (P-values for trend = 0.0028 and 0.0103, respectively). Quitting (versus daily smoking) showed a small reduced risk (stopped for 5+ years: HRone-stage = 0.91, 95% CI = 0.60-1.39, P = 0.66; for former smokers: HRtwo-stage = 0.84, 0.61-1.14, 0.26). CONCLUSIONS: This first IPD meta-analysis from six prospective cohorts in endemic regions has provided robust observational evidence that smoking increased NPC risk in men. NPC should be added to the 12-16 cancer sites known to be tobacco-related cancers. Strong tobacco control policies, preventing young individuals from smoking, would reduce NPC risk in endemic regions.