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Background: The association between smoking and nasopharyngeal carcinoma (NPC) is still uncertain. The aim of this study was to validate smoking effect on NPC and explore if smoking can induce NPC by persistently reactivating EBV in long‐term based on a prospective cohort design. Methods: A NPC screening cohort with 10 181 eligible residents in Sihui city, southern China was conducted from 2008 to 2015. The smoking habit was investigated through the trained interviewers and EBV antibodies (VCA‐IgA, EBNA1‐IgA) as screening markers were tested periodically. New NPC cases were identified through local cancer registry. Cox's regression model was used to estimate the adjusted hazard ratios (aHRs) of smoking on NPC incidence. In the non‐NPC participants, the associations between smoking and EBV seropositivity in different periods were assessed by logistic regression and generalized estimating equations (GEE). Results: With a median of 7.54 years, 71 NPCs were diagnosed ≥1 year after recruitment. Compared with never smokers, the aHRs of developing NPC among ever smokers were 3.00 (95%CI: 1.46‐6.16). Stratified by sex, the HRs of ever smoking were 2.59 (95%CI: 1.07‐6.23) for male and 3.75 (95%CI: 1.25‐11.20) for female, respectively. Among the non‐NPC individuals, ever smoking was not only associated with EBV seropositivity at baseline, but also in the 3‐5 years of follow up, with adjusted odds ratios (aORs) of 1.68 (95%CI: 1.29‐2.18) for VCA‐IgA and 1.92 (95%CI: 1.42‐2.59) for EBNA1‐IgA. Among the smokers who were tested EBV antibodies at least twice, the similar results were obtained using GEE. Conclusion: Smoking could significantly increase the long‐term risk of NPC in southern China, partly by persistently reactivating EBV. [ABSTRACT FROM AUTHOR]

Abstract: The link of nasopharyngeal carcinoma (NPC) with Epstein‐Barr virus (EBV) has been established for decades. Although an abnormal high level of EBV sero‐antibody spectrum and cell‐free circulating EBV DNA loads were exhibited in NPC patients, oral EBV DNA loads, which are primarily responsible for the EBV transmission, has not been previously studied in NPC patients. We conducted an epidemiological study to measure the oral EBV loads, viral components, and the relationship with the serum antibody titers in a large case‐control population (968 cases and 1656 controls) and a family‐based population (91 cases and 165 unaffected family members). EBV DNA loads were detected by quantitative PCR approach targeting the BamHI‐W region. Although a large individualized variation existed, we still observed a decreased oral EBV DNA loads in the population of NPC patients compared to that of healthy controls (ORs were 1.00, 0.69, 0.62, 0.33 classified by the quartiles of viral loads, Ptrend < .001) and family members. In contrast, the elevated levels of oral EBV loads were present in asymptomatic males and elders, suggesting a different important source for EBV transmission. Notably, oral EBV loads were inversely associated with serum antibody titers of VCA‐IgA, EA‐IgA (All Ptrend < .001) in the cases but not in the controls. Our study provides the first epidemiological data of oral EBV loads and viral components in NPC patients and controls in the highest risk area of Southern China, indicating that NPC status is unlikely to be an important determinant of EBV transmission. [ABSTRACT FROM AUTHOR]