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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.

Background: The study aims are to evaluate the associations between nasopharyngeal carcinoma (NPC) risk and cigarette smoking and to explore the effects of cigarette smoking on Epstein-Barr virus (EBV) infection for NPC risk., Methods: 1235 male NPC cases and 1262 hospital-based male controls matched to cases were recruited across six collaborative hospitals between 2010 and 2014. Using a standardized questionnaire, information on cigarette smoking and other potential risk factors for NPC was obtained. Blood was collected and used for anti-EBV VCA IgA and anti-EBV EA-EBNA1 IgA testing using standard methods. Unconditional logistic regression analysis was used to estimate odds ratio (OR) with 95% confidence interval (CI) for each risk factor after adjusting for confounders., Results: 63.6% of cases and 44.0% of controls reported ever smoking cigarettes. After full adjustment, current smokers had a significant 1.60-fold (95% CI = 1.30-1.97) and former smokers a borderline significant 1.27-fold (95% CI = 1.00-1.60) increased NPC risk compared to never smokers. NPC risk increased with increasing duration, intensity, and pack-years of cigarette smoking but not with age at smoking initiation. Among controls, anti-EBV VCA IgA seropositivity rate was higher in current smokers than never smokers (14.0% vs 8.4%; OR = 1.82; 95% CI = 1.19-2.79). Mediation analyses showed that more than 90% of the cigarette smoking effect on NPC risk is mediated through anti-EBV VCA IgA., Conclusion: This study confirms the association between long-term cigarette smoking and NPC and demonstrates that current smoking is associated with seropositivity of anti-EBV VCA IgA antibodies., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Genetic susceptibility is associated with nasopharyngeal carcinoma (NPC). We previously identified rare variants potentially involved in familial NPC and common variants significantly associated with sporadic NPC., Methods: We conducted targeted gene sequencing of 20 genes [16 identified from the study of multiplex families, three identified from a pooled analysis of NPC genome-wide association study (GWAS), and one identified from both studies] among 819 NPC cases and 938 controls from two case-control studies in Taiwan (independent from previous studies). A targeted, multiplex PCR primer panel was designed using the custom Ion AmpliSeq Designer v4.2 targeting the regions of the selected genes. Gene-based and single-variant tests were conducted., Results: We found that NPC was associated with combined common and rare variants in CDKN2A/2B ( P = 1.3 × 10 -4 ), BRD2 ( P = 1.6 × 10 -3 ), TNFRSF19 ( P = 4.0 × 10 -3 ), and CLPTM1L/TERT ( P = 5.4 × 10 -3 ). Such associations were likely driven by common variants within these genes, based on gene-based analyses evaluating common variants and rare variants separately (e.g., for common variants of CDKN2A/2B, P = 4.6 × 10 -4 ; for rare variants, P = 0.04). We also observed a suggestive association with rare variants in HNRNPU ( P = 3.8 × 10 -3 ) for NPC risk. In addition, we validated four previously reported NPC risk-associated SNPs., Conclusions: Our findings confirm previously reported associated variants and suggest that some common variants in genes previously linked to familial NPC are associated with the development of sporadic NPC., Impact: NPC-associated genes, including CLPTM1L/TERT, BRD2 , and HNRNPU , suggest a role for telomere length maintenance in NPC etiology., (©2019 American Association for Cancer Research.)

Background: Although epidemiological and laboratory studies report that chronic inflammatory conditions contribute to the pathogenesis of cancer, it remains controversial whether chronic rhinosinusitis (CRS) results in nasopharyngeal cancer (NPC)., Methods: Retrospective cohort study was performed from the National Health Insurance (NHI) Taiwan database. This study prospectively examined whether CRS or nasal polyposis is associated with NPC risk in the NHI, a population-based cohort of 231,490 Taiwan Chinese individuals with a mean age of 32 years, recruited between 2000 and 2006. We collected information from the Longitudinal Health Insurance Database. Each subject completed an interview including questions about medical conditions, and the NPC occurrence and survival statuses were determined by linkage to population-based NHI registries in Taiwan. In addition, each NPC and CRS subject had completed an interview on medical condition to confirm their diagnosis., Results: After adjustment for age, sex, hypertension, diabetes mellitus, allergic rhinitis, otitis media, coronary artery disease, pharyngitis, and tonsillitis, individuals with rhinosinusitis were found to have a 3.55-fold increased risk of developing NPC compared with individuals without rhinosinusitis (hazard ratio = 3.55; 95% CI = 2.22-5.69). The same results were also observed when the study subjects were analyzed without comorbidities., Conclusion: Adult patients with rhinosinusitis should be followed up with regard to the nasopharynx for at least 3 years, particularly repeat sinusitis patients.

Aim: The cell cycle regulator cyclin D1 (CCND1) is a critical regulator of the G1/S phase transition and plays an important part in several tumor types. This study aimed at investigating the association of CCND1 with and examining the interaction among CCND1 genotype and individual smoking habit in nasopharyngeal carcinoma susceptibility., Patients and Methods: A total of 352 native Taiwanese consisting of 176 cases and 176 controls were enrolled in this hospital-based study, and CCND1 A870G (rs9344) and C1722G (rs678653) genotyping were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and partially verified by direct sequencing., Results: The results showed that there were significant differences between nasopharyngeal carcinoma and control groups in the distribution of the genotypic (p=0.0222) and allelic (p=0.0322) frequencies in the CCND1 A870G genotype. Individuals who carried at least one G allele (GG or AG) had a 0.71-fold lower risk of developing nasopharyngeal carcinoma compared to those who had the AA genotype (95% confidence interval=0.53-0.96). In addition, there is an obvious joint effect of CCND1 A870G genotype with smoking habit on nasopharyngeal carcinoma susceptibility., Conclusion: These findings support the conclusion that the cell cycle regulation may play a role in nasopharyngeal carcinoma development and that CCND1 A870G polymorphism maybe a useful biomarker for nasopharyngeal carcinoma progression.

Background: Caveolin-1 (Cav-1), which has been proposed as a candidate tumor suppressor, plays a regulatory role in several signaling pathways. High expression of Cav-1 in nasopharyngeal carcinoma (NPC) may enhance tumor cell migration and correlate with poor prognosis of the patients, while the genetic alterations of Cav-1 during nasopharyngeal carcinogenesis are still largely unknown. The aim of this study was to evaluate the association between NPC susceptibility and Cav-1 genotypes., Patients and Methods: One hundred and seventy six patients with NPC and 176 age- and gender-matched healthy controls recruited in Taiwan were genotyped and analyzed by PCR-restriction fragment length polymorphism., Results: There were significant differences between the NPC and control groups in the distributions of the genotypic (p=0.0019) and allelic frequencies (p=2.5 10(-4)) in the Cav-1 T29107A (rs7804372) polymorphism., Conclusion: In this first report of Cav-1 involvement in NPC the A allele of Cav-1 T29107A is found to be protective against the development of NPC and may be a novel useful genomic marker for early screening and prediction of NPC.

Conclusion: Patients at risk of developing second primary malignancies (SPMs) comprise those with primary hypopharyngeal, laryngeal, and oral cavity index cancers, patients with well-differentiated squamous cell carcinomas, those aged >70 years, patients who are heavy smokers, alcohol drinkers, or betel quid chewers, and those with a family history of SPM., Objective: SPMs are commonly found after successful treatment of index cancers in the head and neck region; however, treatment guidelines for SPMs have not been established. We compared the differences in the clinical characteristics, treatment outcomes, and 10-year survival rate between patients with SPMs who had been treated for head and neck squamous cell carcinoma (HNSCC) and those who had been treated for nasopharyngeal carcinoma (NPC) in order to establish an effective treatment strategy., Patients and Methods: This was a 10-year retrospective study of 125 patients who had developed SPMs after being treated for either HNSCC or NPC during the period from January 1995 to July 2005. The average follow-up time was 34.9 months, and the setting for the study was a tertiary referral center., Results: The survival rate of patients with SPMs is not significantly poor. The survival is worse if the SPM is associated with a primary advanced stage index cancer or it is synchronous; if the SPM occurs in an area other than the head and neck region; or if SPM patients undergo palliative treatment.