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Cancer has become a major fatal disease in China. The relatively lower early detection rates for multiple cancer types have been one of the main reasons for a relatively lower cancer curative rate in China compared with the developed countries. To investigate trends in the early cancer detection rate over the past 5 years in a major city of China, 45,260 patients with newly diagnosed cancers of the nasopharynx, lung, thyroid, colorectum, liver, breast, uteral cervix, stomach, esophagus, blood, and kidney from 2016 to 2020 at Sun Yat-sen University Cancer Center were evaluated. The early detection rate (stage I disease) for all cancer types in combination significantly increased from 14.4 to 23.07%. Among the studied cancer types, a significant increase in stage I cancers was proportionally seen in cancers of the lung, thyroid, colorectum, and uterine cervix. While for cancers of the liver and stomach, a significant proportional increment was only observed when combining stage I and stage II diseases. No significant alteration in early cancer detection of the nasopharynx, breast, esophagus, blood, or kidney was observed. Three limitations of this present study include relatively small cohorts of cancer patients, relatively short observation periods, and limited sample representativeness. Further efforts are anticipated to validate our findings with larger patient cohorts from different parts of China and enhance early cancer detection rates by promoting public awareness, applying better health care policies, and improving insurance coverage and medical resources. [ABSTRACT FROM AUTHOR]

Introduction: Prospective evidence for herbal diet and nasopharyngeal carcinoma (NPC) development is absent. We therefore evaluated the associations of herbal soup and herbal tea with NPC in a prospective cohort study in southern China. Methods: Based on an NPC screening cohort established in 2008–2015, information on herbal diet consumption, potential confounding factors, and Epstein-Barr virus (EBV) antibody levels were collected from 10,179 individuals aged 30–69 years in Sihui city, southern China. Cox regression models were performed to examine herbal diet with NPC risk, and logistic regression models were used to examine herbal diet with EBV reactivation. Results: During a median of 7.54 years of follow-up, 69 participants developed NPC. Herbal soup consumption was associated with decreased NPC risk, with HRs of 0.31 (95% confidence interval (CI): 0.15–0.62) for the highest intake frequency and 0.29 (95% CI: 0.16–0.51) for a longer duration. However, herbal tea was not significantly associated. Moreover, we identified herbal soup was inversely associated with EBV seropositivity among all the participants at baseline, with the adjusted ORs being 0.78 (95% CI: 0.65–0.93) for immunoglobulin A antibodies against EBV capsid antigens (VCA-IgA) and 0.76 (95% CI: 0.64–0.91) for nuclear antigen 1 (EBNA1-IgA) in those with the highest frequency and 0.70 (95% CI: 0.59–0.84) for VCA-IgA and 0.64 (95% CI: 0.54–0.77) for EBNA1-IgA in those with the longer duration. Inverse associations were also observed in non-NPC individuals. Conclusions: With inhibition of EBV reactivation by plants, herbal soup could significantly decrease the risk of NPC in endemic areas. [ABSTRACT FROM AUTHOR]

Using Epstein-Barr virus (EBV)-based markers to screen populations at high risk for nasopharyngeal carcinoma (NPC) is an attractive preventive approach. Here, we develop a comprehensive risk score (CRS) that combines risk effects of EBV and human genetics for NPC risk stratification and validate this CRS within an independent, population-based dataset. Comparing the top decile with the bottom quintile of CRSs, the odds ratio of developing NPC is 21 (95% confidence interval: 12–37) in the validation dataset. When combining the top quintile of CRS with EBV serology tests currently used for NPC screening in southern China, the positive prediction value of screening increases from 4.70% (serology test alone) to 43.24% (CRS plus serology test). By identifying individuals at a monogenic level of NPC risk, this CRS approach provides opportunities for personalized risk prediction and population screening in endemic areas for the early diagnosis and secondary prevention of NPC. Epstein-Barr virus (EBV) is associated with high risk for nasopharyngeal carcinoma (NPC). Here, the authors develop a comprehensive risk score that combines risk effects of EBV and human genetics for NPC risk stratification. [ABSTRACT FROM AUTHOR]

BACKGROUND: The potential role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high‐incidence areas. METHODS: The authors conducted a population‐based case‐control study, consisting of 2514 incident NPC cases and 2586 randomly selected population controls, in southern China from 2010 to 2014. Occupational history and other covariates were self‐reported using a questionnaire. Multivariate logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with occupational exposures. Restricted cubic splines were used to evaluate potentially nonlinear duration‐response relations. RESULTS: Individuals who had exposure to occupational dusts (OR, 1.45; 95% CI, 1.26‐1.68), chemical vapors (OR, 1.37; 95% CI, 1.17‐1.61), exhausts/smokes (OR, 1.42; 95% CI, 1.25‐1.60), or acids/alkalis (OR, 1.56; 95% CI, 1.30‐1.89) in the workplace had an increased NPC risk compared with those who were unexposed. Risk estimates for all 4 categories of occupational exposures appeared to linearly increase with increasing duration. Within these categories, occupational exposure to 14 subtypes of agents conferred significantly higher risks of NPC, with ORs ranging from 1.30 to 2.29, including dust from metals, textiles, cement, or coal; vapor from formaldehyde, organic solvents, or dyes; exhaust or smoke from diesel, firewood, asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric acid, nitric acid, and concentrated alkali/ammonia. CONCLUSIONS: Occupational exposures to dusts, chemical vapors, exhausts/smokes, or acids/alkalis are associated with an excess risk of NPC. If the current results are causal, then the amelioration of workplace conditions might alleviate the burden of NPC in endemic areas. LAY SUMMARY: The role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high‐incidence areas.The authors conducted a population‐based study with 2514 incident NPC cases and 2586 population controls in southern China and observed that occupational exposures were associated with an increased risk of NPC.Duration‐response trends were observed with increasing duration of exposure.These findings provide new evidence supporting an etiologic role of occupational exposures for NPC in a high‐incidence region. Occupational exposures are associated with an increased risk of nasopharyngeal carcinoma, and the association is primarily driven by 14 subtypes of occupational agents. Duration‐response trends are observed with increasing duration of exposure. [ABSTRACT FROM AUTHOR]

Objective: Plasma Epstein-Barr virus (EBV) DNA is considered a biomarker for nasopharyngeal carcinoma (NPC). However, its long-term role in NPC development is unclear.Materials and Methods: A total of 1363 participants seropositive for EBV VCA-IgA and EBNA1-IgA in a community-based NPC screening program in southern China were tested for plasma EBV DNA levels by real-time qPCR between 2008 and 2015. New NPC cases were confirmed by active follow-up approach and linkage to local cancer registry through the end of 2016. Cox proportional hazards regression analysis was performed to calculate the hazard ratios (HRs) for NPC risk with plasma EBV DNA.Results: Thirty patients were newly diagnosed during a median 7.5 years follow-up. NPC incidence increased with the plasma EBV DNA load ranging from 281.46 to 10,074.47 per 100,000 person-years in participants with undetectable and ≥ 1000 copies/ml levels; the corresponding cumulative incidence rates were 1.73 and 50%. Furthermore, plasma EBV DNA loads conferred an independent risk for NPC development after adjustment for other risk factors, with HRs of 7.63 for > 3-999 copies/ml and 39.79 for ≥1000 copies/ml. However, the HRs decreased gradually after excluding NPC cases detected in the first 2 to 3 years and became statistically nonsignificant by excluding cases detected during the first 4 years.Conclusion: Elevated plasma EBV DNA can predict NPC risk over 3 years. Monitoring plasma EBV DNA can be used as a complementary approach to EBV serological antibody-based screening for NPC. [ABSTRACT FROM AUTHOR]

Background: An association between a nonmedicinal herbal diet and nasopharyngeal carcinoma (NPC) has often been hypothesized but never thoroughly investigated.Methods: This study enrolled a total of 2469 patients with incident NPC and 2559 population controls from parts of Guangdong and Guangxi Provinces in southern China between 2010 and 2014. Questionnaire information was collected on the intake of traditional herbal tea and herbal soup as well as the specific herbal plants used in soups and other potentially confounding lifestyle factors. Multivariate logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the NPC risk in association with herbal tea and soup intake.Results: Ever consumption of herbal tea was not associated with NPC risk (OR, 1.03; 95% CI, 0.91-1.17). An inverse association was observed for NPC among ever drinkers of herbal soup (OR, 0.78; 95% CI, 0.67-0.90) but without any monotonic trend with an increasing frequency or duration of herbal soup consumption. Inverse associations with NPC risk were detected with 9 herbal plants used in herbal soup, including Ziziphus jujuba, Fructus lycii, Codonopsis pilosula, Astragalus membranaceus, Semen coicis, Smilax glabra, Phaseolus calcaratus, Morinda officinalis, and Atractylodes macrocephala (OR range, 0.31-0.79).Conclusions: Consuming herbal soups including specific plants, but not herbal tea, was inversely associated with NPC. If replicated, these results might provide potential for NPC prevention in endemic areas. [ABSTRACT FROM AUTHOR]

Background: Chinese-style salted fish intake in early life is considered an established risk factor for nasopharyngeal carcinoma (NPC). However, results for adult intakes of salted fish and preserved foods are inconsistent.Objective: The aim of this study was to ascertain the relations of Chinese-style hard and soft salted fish and preserved food intakes with NPC risk.Methods: We conducted a population-based case-control study in southern China with 2554 NPC cases identified through a rapid case ascertainment system and 2648 healthy controls, frequency-matched on age, sex, and area. Subjects (aged 20-74 y) were interviewed via a food-frequency questionnaire, including information on portion size. Data were also collected on alcohol consumption and potential confounders. Food intake was grouped into 3-5 energy-adjusted intake levels during adulthood (10 y prior) and adolescence (16-18 y). For childhood (at age 10 y), intake frequency of selected food items was collected. Multivariate-adjusted ORs with 95% CIs were estimated via logistic regression.Results: We found no association between NPC and intake of hard Chinese-style salted fish during adulthood, and an increased risk at the highest level of intake during adolescence (OR: 1.19; 95% CI: 1.03, 1.39). In contrast, we found a decreased risk for the middle intake level of soft salted fish during adulthood (OR: 0.68; 95% CI: 0.57, 0.81) and adolescence (OR: 0.71; 95% CI: 0.59, 0.85). Preserved foods showed contrasting risk profiles, e.g., the highest adult intake level of salted egg (OR: 1.51; 95% CI: 1.22, 1.87) and fermented black beans (OR: 0.67; 95% CI: 0.56, 0.80). Associations with NPC were weaker than previously reported, e.g., for weekly childhood intake of salted fish (OR: 1.56; 95% CI: 1.24, 1.97).Conclusions: Hard and soft salted fish have different risk profiles. Salted fish and other preserved foods were at most weak risk factors for NPC in all periods and may play a smaller role in NPC occurrence than previously thought. [ABSTRACT FROM AUTHOR]

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]

Whether the association between body size or shape and nasopharyngeal carcinoma (NPC) risk exists or varies by age‐specific body size indicators is unclear. In a population‐based case–control study conducted in Southern China between 2010 and 2014, self‐reported height, weight, and body shape at age 20 and 10 years before interview were collected from 2448 histopathologically confirmed NPC cases and 2534 population‐based controls. Body mass index (BMI) was categorized according to the World Health Organization guidelines for Asian populations: underweight (<18.5 kg/m2), normal weight (18.5‐22.9 kg/m2), overweight (23.0‐27.4 kg/m2), and obese (≥27.5 kg/m2). Multivariate odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression. Furthermore, restricted cubic spline analysis was employed to examine nonlinear effects of BMI and body shape as continuous covariates. Underweight vs normal weight at age 20 years was associated with a 22% decreased NPC risk (OR, 0.78; 95% CI, 0.67, 0.90), whereas obesity was not significantly associated with NPC risk. Associations with BMI 10 years before the interview were similar. Having the leanest body shape at age 20 years, compared with the mode was not significantly associated with NPC risk (OR, 0.85; 95% CI, 0.62, 1.16), but having a larger body shape was associated with an elevated risk (OR, 1.25; 95% CI, 1.03, 1.52). Increasing BMI revealed positive trends with NPC risk. Despite some indication of significant findings, evidence for a strong association between BMI or body shape and NPC risk is still limited. [ABSTRACT FROM AUTHOR]

Background: Oral Epstein-Barr virus (EBV) status reflects host EBV activity and potentially links to EBV-associated diseases, however, factors influencing oral EBV loads or reactivation, such as environmental exposures or host factors, are not fully understood.Methods: A 2-stage, multicenter, cross-sectional study of 6558 subjects from 21 administrative cities of southern China and 3 populations from representative geographical areas in China (referred to as the south, north, and northeastern populations) was performed. The relationships between demographical factors and environmental exposures to EBV loads were analyzed by logistic regression models.Results: Current smoking, with a dose-response effect, was found to be strongly associated with higher oral EBV loads in the pooled data, with an odds ratio of 1.58 (95% confidence interval, 1.39-1.79), as well as in each of the separate populations. The odds ratio increased to 3.06 when current smokers in southern China were compared to never smokers in northern China. Additionally, higher oral EBV loads tended to be detected in older participants, male participants, and participants in southern China.Conclusions: This study provided evidence linking the effect of host-environmental factors, particularly smoking, to oral EBV activity. It could strengthen our understanding of the possible causal roles of EBV-related diseases, which may help to prevent or mitigate EBV-associated diseases. [ABSTRACT FROM AUTHOR]

Because persistent inflammation may render the nasopharyngeal mucosa susceptible to carcinogenesis, chronic ear-nose-throat (ENT) disease and its treatment might influence the risk of nasopharyngeal carcinoma (NPC). Existing evidence is, however, inconclusive and often based on methodologically suboptimal epidemiologic studies. In a population-based case-control study in southern China, we enrolled 2,532 persons with NPC and 2,597 controls, aged 20–74 years, from 2010 to 2014. Odds ratios were estimated for associations between NPC risk and history of ENT and related medications. Any history of chronic ENT disease was associated with a 34% increased risk of NPC. Similarly, use of nasal drops or aspirin was associated with approximately doubled risk of NPC. However, in secondary analyses restricted to chronic ENT diseases and related medication use at least 5 years prior to diagnosis/interview, most results were statistically nonsignificant, except a history of uncured ENT diseases, untreated nasal polyps, and earlier age at first diagnosis of ENT disease and first or most recent aspirin use. Overall, these findings suggest that ENT disease and related medication use are most likely early indications rather than causes of NPC, although the possibility of a modestly increased NPC risk associated with these diseases and related medications cannot be excluded. [ABSTRACT FROM AUTHOR]

Background: To the authors' knowledge, no studies to date have explored familial risks of nasopharyngeal carcinoma (NPC) in detail and quantified its lifetime risk in high-incidence populations.Methods: The authors conducted a population-based case-control study of 2499 NPC cases and 2576 controls randomly selected in southern China from 2010 through 2014. Unconditional logistic regression was used to estimate multivariable-adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) associated with a family history of NPC. In addition, the authors compiled a reconstructed cohort comprising 40,781 first-degree relatives of cases and controls to calculate the lifetime cumulative risk of NPC.Results: Individuals with a first-degree family history of NPC were found to be at a >4-fold risk of NPC (OR, 4.6; 95% CI, 3.5-6.1) compared with those without such a history, but had no excess risk of other malignancies. The excess risk was higher for a maternal than a paternal history and was slightly stronger for a sibling compared with a parental history, and for a sororal than a fraternal history. Among relatives of cases, the cumulative risk of NPC up to age 74 years was 3.7% (95% CI, 3.3%-4.2%), whereas that among relatives of controls was 0.9% (95% CI, 0.7%-1.2%). Cumulative risk was higher in siblings than in parents among relatives of cases, whereas no such difference was noted among relatives of controls.Conclusions: Individuals with a family history of NPC have a substantially higher risk of NPC. These relative and cumulative risk estimates can guide the development of strategies for early detection and clinical consultation in populations with a high incidence of NPC. Cancer 2017;123:2716-25. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) is one of the risk factors of nasopharyngeal carcinoma (NPC), and understanding the modifiable risk factors of EBV activation is crucial in the prevention of NPC. In this study, we aimed to investigate the association between solid fuel use and EBV seropositivity in a high-risk area of NPC. Our study was based on the baseline findings from an ongoing population-based prospective cohort in Sihui county in Southern China. We explored the association between current use of solid fuel in cooking and EBV seropositivity, and NPC-related EBV activation, using logistic regression models. Stratification analyses were further conducted to assess potential effect modifiers. We also examined the impact of frequency and duration of solid fuel use, and switch in fuel types, on EBV seropositivity among ever users. Of the 12,579 participants included in our analysis, 4088 (32.5%) were EBV seropositive and 421 (3.3%) were high risk for NPC-related EBV activation. Solid fuel use was associated with a higher risk of EBV seropositivity and NPC-related EBV activation, with odds ratios (ORs) of 1.33 (95%CI: 1.01, 1.76) and 1.81 (95%CI: 1.03, 3.18), respectively. Higher risk of EBV seropositivity was observed for those who did not use ventilation apparatus and those who consumed salted food. Among ever users, OR was highest for participants with more than 40 years of solid fuel exposure (1.17, 95%CI: 1.00–1.37) and who have been constantly using solid fuel (1.30, 95%CI: 0.96–1.75). We did not find a statistically significant impact of cooking frequency on EBV seropositivity. The identification of solid fuel as a risk factor for EBV activation is of great value for understanding the etiology of NPC. Our findings also have important public health implications given the fact that a third of the global population still lack access to clean cooking, especially in low resource settings. [Display omitted] • Solid fuel is associated with increased risk of EBV seropositivity and activation. • For ever-users, largest effect in those using solid fuel constantly over 40 years. • High risk of solid fuel among ventilator nonusers and those who consume salted food. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents Liu Z, Ji MF, Huang QH's response to the invitory commentary on the article 'Two Epstein-Barr virus–related serologic antibody tests in nasopharyngeal carcinoma (NPC) screening: results from the initial phase of a cluster randomized controlled trial in southern China' by Dr. Hildesheim. The article also discusses risk prediction model incorporating other risk factors can be used to improve the efficiency of NPC screening in both endemic and nonendemic areas.

Objects: Nasopharyngeal carcinoma (NPC) incidence exhibits a remarkable sex disparity, with higher risk among males. Whether this pattern can be partly explained by female reproductive history is unclear.Methods: A population-based case-control study of NPC was conducted in southern China between 2010 and 2014, including 674 histopathologically verified female NPC cases and 690 female controls randomly selected from population-based registries. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression after adjusting for potential confounders.Results: Women who had 3, 4, or ≥5 pregnancies compared with 2 pregnancies were at significantly increased risk for NPC (ORs 1.56, 1.45 and 1.88, respectively). History of deliveries was similarly associated with a greater risk of NPC. These positive associations were more prominent in women who were younger than 50 years, had less than 10 years of education, or were white-collar workers. Increasing time since menopause was associated with a diminished NPC risk (Ptrend = 0.010). Women more than 15 years after menopause had a 0.35-fold (95% CI: 0.16-0.75) NPC risk compared with those 0-3 years after menopause.Conclusion: Contrary to our hypothesis, a history of pregnancy or delivery increased the risk of NPC and the risk decreased with increasing time since menopause. However, the non-linear relationship and no consistent risk patterns across strata indicate that the observed associations are unlikely to be causal, and may at least partially be ascribed to residual confounding by socioeconomic factors. [ABSTRACT FROM AUTHOR]

• Association of nasopharyngeal carcinoma (NPC) with lifelong residential exposures. • A population-based study of 2533 incident NPC cases and 2597 population controls. • Poorer residential conditions were associated with an increased risk of NPC. • Risk of NPC was stronger for residential exposures at an earlier age. • Risk of NPC increased with increasing duration of residential exposures. Given the role of exposures related to residence in the development of nasopharyngeal carcinoma (NPC) has not been well explored, present study aims to investigate the magnitude and pattern of associations for NPC with lifelong residential exposures. We carried out a multi-center, population-based case-control study with 2533 incident NPC cases and 2597 randomly selected population controls in southern China between 2010 and 2014. We performed multivariate logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with residential exposures. Compared with those living in a building over lifetime, risk of NPC was higher for individuals living in a cottage (OR: 1.56; 95% CI: 1.34–1.81) or in a boat (3.87; 2.07–7.21). NPC risk was also increased in individuals using wood (1.34; 1.03–1.75), coal (1.70; 1.17–2.47), or kerosene (3.58; 1.75–7.36) vs. using gas/electricity as cooking fuel; using well water (1.57; 1.34–1.83), river water (1.80; 1.47–2.21), or spring/pond/stream water (2.03; 1.70–2.41) vs. tap water for source of drinking water; living in houses with smaller-sized vs. larger windows in the bedroom (3.08; 2.46–3.86), hall (1.89; 1.55–2.31) or kitchen (1.67; 1.34–2.08); and increasing exposure to cooking smoke [(1.53; 1.20–1.94) for high exposure)] or burned incense [(1.59; 1.31–1.95) for daily use)]. Weighted Cox regression analysis corroborated these results. Poorer residential conditions and household air pollution are associated with an increased risk of NPC. Large-scale studies in other populations or longitudinal studies are warranted to further corroborate these findings. [ABSTRACT FROM AUTHOR]

Background: Screening with anti-Epstein-Barr virus (EBV) serology and endoscopy decreased nasopharyngeal carcinoma (NPC) mortality in Guangdong in a randomized trial. We conducted a secondary analysis of this trial using local incidence and cost data to optimize screening programs, hypothesizing that screening could be cost-effective in southern China., Methods: Screening costs and life-years after NPC diagnosis were obtained from the Guangdong trial's intent-to-screen population (men and women aged 30-69). Seropositive subjects were rescreened annually for 5 years. Thereafter, we evaluated 12 screening strategies in Guangdong and Guangxi using a validated model. Strategies used combinations of serology, nasopharyngeal swab PCR (NP PCR), endoscopy, and MRI from trial subcohorts. Incidence data and costs were obtained from local cancer registries and the provincial healthcare system., Results: In the intent-to-screen population, screening with serology and endoscopy was cost-effective (¥42,366/life-year, 0.52 GDP per capita). Screening for 5 to 15 years between ages 35 and 59 years met a willingness-to-pay threshold of 1.5 GDP/quality-adjusted life-years in all modeled populations. Despite doubling costs, adding MRI could be cost-effective via improved sensitivity. NP PCR triage reduced endoscopy/MRI referrals by 37%. One-lifetime screen could reduce NPC mortality by approximately 20%., Conclusions: EBV-based serologic screening for NPC is likely to be cost-effective in southern China. Among seropositive subjects, the preferred strategies use endoscopy alone or selective endoscopy triaged by MRI with or without NP PCR. These data may aid the design of screening programs in this region., Impact: These findings support population-based screening in southern China by defining the target population, cost-effectiveness, and optimized screening approach., (©2024 American Association for Cancer Research.)

While Epstein-Barr virus (EBV) is the major cause of nasopharyngeal carcinoma (NPC), the value of the humoral immune response to EBV glycoproteins and NPC development remains unclear. Correlation between antiglycoprotein antibody levels, neutralization of EBV infectivity, and the risk of NPC requires systematic study. Here, we applied a cytometry-based method and enzyme-linked immunosorbent assay to measure neutralization of infectivity and antibody response to EBV glycoproteins (gH/gL, gB, gp350, and gp42) of plasma samples from 20 NPC cases and 20 high-risk and 20 low-risk healthy controls nested within a screening cohort in Sihui, southern China. We found that NPC cases have similar plasma neutralizing activity in both B cells and epithelial cells and EBV glycoprotein-specific IgA and IgG antibody levels compared with those of healthy controls. Significant correlations were observed between gH/gL IgG and gB IgG and the neutralizing ability against EBV infection of epithelial cells and B cells. These results indicate that a high level of glycoprotein antibodies may favor protection against primary EBV infection, instead of being low-risk biomarkers for NPC in long-term EBV-infected adults. In conclusion, this study provides novel insights into the humoral immune response to EBV infection and NPC development, providing valuable leads for future research that is important for prevention and treatment of EBV-related diseases. IMPORTANCE Epstein-Barr virus (EBV) is a human oncogenic gammaherpesvirus that infects over 90% of humans in the world and is causally associated with a spectrum of epithelial and B-cell malignancies such as nasopharyngeal carcinoma (NPC). A prophylactic vaccine against EBV is called for, but no approved vaccine is available yet. Therefore, EBV remains a major public health concern. To facilitate novel vaccines and therapeutics for NPC, it is of great importance to explore the impact of humoral immune response to EBV glycoproteins before the development of NPC. Therefore, in this study, we systematically assessed the correlation between antiglycoprotein antibody levels, neutralization of EBV infectivity, and the risk of NPC development. These results provide valuable information that will contribute to designing effective prevention and treatment strategies for EBV-related diseases such as NPC., (Copyright © 2020 Zhu et al.)

Epstein-Barr virus (EBV) infection is ubiquitous worldwide and is associated with multiple cancers, including nasopharyngeal carcinoma (NPC). The importance of EBV viral genomic variation in NPC development and its striking epidemic in southern China has been poorly explored. Through large-scale genome sequencing of 270 EBV isolates and two-stage association study of EBV isolates from China, we identify two non-synonymous EBV variants within BALF2 that are strongly associated with the risk of NPC (odds ratio (OR) = 8.69, P = 9.69 × 10 -25 for SNP 162476&#95;C; OR = 6.14, P = 2.40 × 10 -32 for SNP 163364&#95;T). The cumulative effects of these variants contribute to 83% of the overall risk of NPC in southern China. Phylogenetic analysis of the risk variants reveals a unique origin in Asia, followed by clonal expansion in NPC-endemic regions. Our results provide novel insights into the NPC endemic in southern China and also enable the identification of high-risk individuals for NPC prevention.

Cancer is the leading cause of death in China and depicting the cancer pattern of China would provide basic knowhows on how to tackle it more effectively. In this study we have reviewed several reports of cancer burden, including the Global cancer statistics 2018 and Cancer statistics in China, 2015, along with the GLOBCAN 2018 online database, to investigate the differences of cancer patterns between China, the United States (USA) and the United Kingdom (UK). An estimated 4.3 million new cancer cases and 2.9 million new cancer deaths occurred in China in 2018. Compared to the USA and UK, China has lower cancer incidence but a 30% and 40% higher cancer mortality than the UK and USA, among which 36.4% of the cancer-related deaths were from the digestive tract cancers (stomach, liver, and esophagus cancer) and have relatively poorer prognoses. In comparison, the digestive cancer deaths only took up ≤ 5% of the total cancer deaths in either USA or UK. Other reasons for the higher mortality in China may be the low rate of early-stage cancers at diagnosis and non-uniformed clinical cancer treatment strategies performed by different regions. China is undergoing the cancer transition stage where the cancer spectrum is changing from developing country to developed country, with a rapidly increase cancer burden of colorectal, prostate, female breast cancers in addition to a high occurrence of infection-related and digestive cancers. The incidence of westernized lifestyle-related cancers in China (i.e. colorectal cancer, prostate, bladder cancer) has risen but the incidence of the digestive cancers has decreased from 2000 to 2011. An estimated 40% of the risk factors can be attributed to environmental and lifestyle factors either in China or other developed countries. Tobacco smoking is the single most important carcinogenic risk factor in China, contributing to ~ 24.5% of cancers in males. Chronic infection is another important preventable cancer contributor which is responsible for ~ 17% of cancers. Comprehensive prevention and control strategies in China should include effective tobacco-control policy, recommendations for healthier lifestyles, along with enlarging the coverage of effective screening, educating, and vaccination programs to better sensitize greater awareness control to the general public.

Background: The association of circulating inflammation markers with nasopharyngeal carcinoma (NPC) is still largely unclear. This study aimed to comprehensively explore the relationship between circulating cytokine levels and the subsequent risk of NPC with a two-stage epidemiologic study in southern China., Methods: The serum levels of 33 inflammatory cytokines were first measured in a hospital-based case-control study (150 NPC patients and 150 controls) using multiplex assay platforms. Marker levels were categorized into two or more groups based on the proportion of sample measurements that was above the lower limit of detection. Odds ratios (ORs) and 95% confidence intervals (CIs) relating the serum marker concentration to the risk of NPC were computed by multivariable logistic regression models. The associations were validated in 60 patients with NPC and 120 controls in a subsequent nested case-control study within a NPC screening trial. Potential interactions between serum cytokines and Epstein-Barr virus (EBV) relating to the risk of NPC were assessed using a likelihood ratio test., Results: The levels of serum macrophage inflammatory protein (MIP)-1α and MIP-1β in the highest categories were associated with a decreased risk of NPC in both the case-control study (MIP-1α: OR = 0.49, 95% CI = 0.26-0.95; MIP-1β: OR = 0.47, 95% CI = 0.22-1.00) and the nested case-control study (MIP-1α: OR = 0.13, 95% CI = 0.03-0.62; MIP-1β: OR = 0.20, 95% CI = 0.04-0.94), compared with those in the lowest categories. Furthermore, individuals with lower levels of these two cytokine markers who were EBV seropositive presented with a largely higher risk of NPC compared with patients with higher levels who were EBV seronegative in both the case-control study (MIP-1α: OR = 16.28, 95% CI = 7.11-37.23; MIP-1β: OR = 12.86, 95% CI = 5.9-28.05) and the nested case-control study (MIP-1α: OR = 86.12, 95% CI = 10.58-701.03; MIP-1β: OR = 115.44, 95% CI = 13.92-957.73)., Conclusions: Decreased preclinical MIP-1α and MIP-1β levels might be associated with a subsequently increased risk of NPC. More mechanistic studies are required to fully understand this finding.

Our previous study found that smoking was associated with an elevated level of the antibody against VCA in the Epstein-Barr virus (EBV) lytic phase, which was an important predictive marker of the risk of nasopharyngeal carcinoma (NPC). It remained unknown whether environmental factors were associated with the levels of other EBV antibodies, such as Zta-IgA, EA-IgA, EBNA1-IgA, and LMP1-IgA, in the lytic and latent infection periods. We aimed to investigate the possible environmental inducers that could affect EBV antibody levels in two independent healthy male populations from endemic NPC areas in South China (N=1498) and non-endemic NPC areas in North China (N=1961). We performed ELISA and immunoenzymatic assays to test the levels of antibodies specific to the EBV antigens. The seropositive rates of antibodies against the antigens expressed in both the EBV latent and lytic infection periods, namely, LMP1-IgA, EBNA1-IgA, and Zta-IgA, in endemic areas (28.65%, 5.43% and 14.49%, respectively) were significantly higher than those in non-endemic areas (14.43%, 1.07% and 6.32%, respectively). Smoking was associated with higher seropositivity for EBNA1-IgA (OR=1.47, 95% CI=1.12-1.93) and Zta-IgA (OR=1.28, 95% CI=0.99-1.66), with dose-response effects, while not associated with the levels of LMP1-IgA. In conclusion, smoking was an important environmental factor, which associated with increased levels of EBNA1-IgA, and Zta-IgA., (Copyright © 2018 German Center for Neurodegenerative Diseases (DZNE). Published by Elsevier B.V. All rights reserved.)

Objective: Seven recombinant viral capsid antigen-IgA (VCA-IgA) ELISA kits are widely used in China, but their diagnostic effects have not been evaluated. In this study, we evaluated whether the diagnostic effects of these kits are similar to those of the standard kit (EUROIMMUN, Lübeck, Germany)., Methods: A diagnostic case-control trial was conducted with 200 cases of nasopharyngeal carcinoma (NPC) and 200 controls from NPC-endemic areas in southern China. The areas under the curve (AUCs), the sensitivities and the specificities of testing kits were compared with those of the standard kit. The test-retest reliability of each kit was determined by intraclass correlation coefficient (ICC). Their diagnostic accuracy in combination with Epstein-Barr virus nuclear antigen 1-IgA (EBNA1-IgA) was also evaluated in logistic models., Results: Three testing kits-BB, HA and KSB-showed diagnostic accuracy equal to that of the standard kit, with good performance in the AUCs (0.926-0.945), and no significant differences in sensitivity were found between early-stage and advanced-stage NPCs. ICCs exceeded 0.8. Three logistic regression models were built, and the AUCs of these models (0.961-0.977) were better than those of the individual VCA-IgA kits. All new models had diagnostic accuracy equal to that of the standard kit. New cut-off values of these three kits and their corresponding combinations for researchers to replicate and use in NPC early detection and screening in the future were provided., Conclusions: Three recombinant VCA-IgA kits-BB,HA and KSB-had diagnostic effects equal to those of the standard kit, and, in combination with EBNA1-IgA in logistic regression models, can be used in future screening for NPC., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The magnitude and patterns of associations between smoking and risk of nasopharyngeal carcinoma (NPC) in high-incidence regions remain uncertain. Associations with active and passive tobacco smoking were estimated using multivariate logistic regression in a population-based case-control study of 2,530 NPC cases and 2,595 controls in Guangdong and Guangxi, southern China, in 2010-2014. Among men, risk of NPC was significantly higher in current smokers compared with never smokers (odds ratio (OR) = 1.32, 95% confidence interval (CI): 1.14, 1.53) but not in former smokers (OR = 0.92, 95% CI: 0.73, 1.17). Risk increased with smoking intensity (per 10 cigarettes/day, OR = 1.09, 95% CI: 1.03, 1.16), smoking duration (per 10 years, OR = 1.11, 95% CI: 1.06, 1.16), and cumulative smoking (per 10 pack-years, OR = 1.08, 95% CI: 1.04, 1.12). Risk decreased with later age at smoking initiation (per year, OR = 0.97, 95% CI: 0.96, 0.98) but not greater time since smoking cessation. Exposures to passive smoking during childhood (OR = 1.24, 95% CI: 1.03, 1.48) and from a spouse during adulthood (OR = 1.30, 95% CI: 1.03, 1.63) were independently associated with increased NPC risk in never-smoking men and women, but exposure-response trends were not observed. In conclusion, active and passive tobacco smoking are associated with modestly increased risk of NPC in southern China; risk is highest among long-term smokers., (© The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The association between oral health and risk of nasopharyngeal carcinoma (NPC) is largely unknown. Further understanding could shed light on potential pathogenic mechanisms and preventive measures., Methods: We conducted a population-based case-control study in southern China between 2010 and 2014. We enrolled 2,528 incident NPC cases, aged 20-74 years, and 2,596 controls, randomly selected from the total population registers, with frequency matching to the 5-year age and sex distribution of the cases by geographic region. We interviewed subjects using a structured questionnaire inquiring about oral health indicators and potential confounding factors. We used unconditional logistic regression to estimate multivariate-adjusted ORs with 95% confidence intervals (CI)., Results: A higher number of filled teeth was associated with an elevated risk of NPC. Individuals with 1 to 3 and more than 3 teeth filled versus none had adjusted ORs of 1.25 (95% CI, 1.06-1.49) and 1.55 (95% CI, 1.13-2.12), respectively (Ptrend = 0.002). Conversely, the adjusted OR for those who brushed teeth twice or more per day versus once or less per day was 0.62 (95% CI, 0.55-0.70). We detected a borderline significant positive association with earlier age at first adult tooth loss., Conclusion: Our study suggested a positive association between some indicators of poor oral health and risk of NPC. Further studies are needed to confirm whether the findings are causal and, if so, to further explain the underlying mechanisms., Impact: Improvement of oral hygiene might contribute to reducing NPC risk. Cancer Epidemiol Biomarkers Prev; 25(8); 1201-7. ©2016 AACR., (©2016 American Association for Cancer Research.)

Background: Epstein-Barr virus (EBV) commonly infects the general population and has been associated with nasopharyngeal carcinoma (NPC), which has a high incidence in certain regions. This study aimed to address how EBV variations contribute to the risk of NPC., Methods: Using logistic regression analysis and based on the sequence variations at EBV-encoded RPMS1, a multi-stage association study was conducted to identify EBV variations associated with NPC risk. A protein degradation assay was performed to characterize the functional relevance of the RPMS1 variations., Results: Based on EBV-encoded RPMS1 variations, a single nucleotide polymorphism (SNP) in the EBV genome (locus 155391: G>A, named G155391A) was associated with NPC in 157 cases and 319 healthy controls from an NPC endemic region in South China [P < 0.001, odds ratio (OR) = 4.47, 95% confidence interval (CI) 2.71-7.37]. The results were further validated in three independent cohorts from the NPC endemic region (P < 0.001, OR = 5.20, 95% CI 3.18-8.50 in 168 cases vs. 241 controls, and P < 0.001, OR = 5.27, 95% CI 4.06-6.85 in 726 cases vs. 880 controls) and a non-endemic region (P < 0.001, OR = 7.52, 95% CI 3.69-15.32 in 58 cases vs. 612 controls). The combined analysis in 1109 cases and 2052 controls revealed that the SNP G155391A was strongly associated with NPC (P(combined) < 0.001, OR = 5.27, 95% CI 4.31-6.44). Moreover, the frequency of the SNP G155391A was associated with NPC incidence but was not associated with the incidences of other EBV-related malignancies. Furthermore, the protein degradation assay showed that this SNP decreased the degradation of the oncogenic RPMS1 protein., Conclusions: Our study identified an EBV variation specifically and significantly associated with a high risk of NPC. These findings provide insights into the pathogenesis of NPC and strategies for prevention.

Background: Whether or not hepatitis B virus (HBV) infection plays a role in the development of nasopharyngeal carcinoma (NPC) is largely unknown. Our study aimed to assess the association between HBV infection and the risk of NPC in Southern China., Methods: We conducted a case-control study including 711 NPC cases and two groups of controls. The first control group consisted of 656 individuals with other benign tumors unrelated to HBV infection and the second group consisted of 680 healthy population controls. Multivariable ORs and corresponding 95% confidence intervals (CI) for NPC were estimated by logistic regression., Results: Patients with NPC had higher prevalence of antibodies against hepatitis B core antigen-positive [anti-HBc-(+); 47.26%] compared with either benign tumor controls (39.33%; P < 0.01) or healthy controls (41.18%; P = 0.04). In multivariable models adjusting for a set of risk factors for NPC, anti-HBc-(+) was significantly associated with a higher risk of NPC [adjusted OR (AOR), 1.40; 95% CI, 1.12-1.74 compared with the benign tumor controls and AOR, 1.48; 95% CI, 1.05-2.08 compared with the healthy controls]. The association was not modified by hepatitis B surface antigen (HBsAg) status. Finally, compared with the healthy controls, individuals with both anti-HBc-(+) and EBV antibodies had largely increased risk of NPC (AOR, 141.82; 95% CI, 68.73-292.62)., Conclusion: Our study suggests that HBV infection is associated with NPC risk in Southern China., Impact: Prevention for HBV infection may play a role in the development of NPC., (©2015 American Association for Cancer Research.)

Introduction: In the past several decades, declining incidences of nasopharyngeal carcinoma (NPC) have been observed in Chinese populations in Hong Kong, Taiwan, Los Angeles, and Singapore. A previous study indicated that the incidence of NPC in Sihui County, South China remained stable until 2002, but whether age, diagnosis period, and birth cohort affect the incidence of NPC remains unknown., Methods: Age-standardized rates (ASRs) of NPC incidence based on the world standard population were examined in both males and females in Sihui County from 1987 to 2011. Joinpoint regression analysis was conducted to quantify the changes in incidence trends. A Poisson regression age-period-cohort model was used to assess the effects of age, diagnosis period, and birth cohort on the risk of NPC., Results: The ASRs of NPC incidence during the study period were 30.29/100,000 for males and 13.09/100,000 for females. The incidence of NPC remained stable at a non-significant average annual percent change of 0.2% for males and -1.6% for females throughout the entire period. A significantly increased estimated annual percent change of 6.8% (95% confidence interval, 0.1%-14.0%) was observed from 2003 to 2009 for males. The relative risk of NPC increased with advancing age up to 50-59 and decreased at ages >60 years. The period effect curves on NPC were nearly flat for males and females. The birth cohort effect curve for males showed an increase from the 1922 cohort to the 1957 cohort and a decrease thereafter. In females, there was an undulating increase in the relative risk from the 1922 cohort to the 1972 cohort., Conclusions: The incidence trends for NPC remained generally stable in Sihui from 1987 to 2011, with an increase from 2003 to 2009. The relative risks of NPC increased in younger females.

A nasopharyngeal carcinoma (NPC) mass screening trial using a combination of immunoglobulin A antibodies to Epstein-Barr virus capsid antigen and nuclear antigen-1 by enzyme-linked immunosorbent assay in addition to indirect mirror examination in the nasopharynx and/or lymphatic palpation (IMLP) was conducted in southern China. Cantonese aged 30-59 years residing in 2 cities randomly selected by cluster sampling, Sihui and Zhongshan, were invited to participate in this screening from May 2008 through May 2010. Participants were offered fiberoptic endoscopy examination and/or pathologic biopsy if their serologic tests reached our predefined level of high risk or if results from the physical examination indicated possible cancer (i.e., were IMLP positive). A total of 28,688 individuals were voluntarily screened in the initial round. The overall NPC detection rate was 0.14% (41/28,688) with an early diagnosis rate of 68.3% (28/41) during the first year of follow-up. Thirty-eight of 41 cases (92.7%) were detected among the high-risk group, and 7 of 41 cases (17.1%) were detected among the IMLP-positive group. The 2 Epstein-Barr virus serologic tests by enzyme-linked immunosorbent assay could be a feasible alternative for NPC screening in endemic areas. Further follow-up is needed to examine whether screening has an effect on decreasing mortality from NPC in these areas.

Objectives: To examine the optimal screening interval among the individuals who received a negative Epstein-Barr virus immunoglobulin A antibodies against viral capsid antigen (VCA-IgA) serum test result and who comprised the majority of the population screened for nasopharyngeal carcinoma (NPC)., Methods: Screening was performed in Sihui, Guangdong, China, offering a repeated screening for participants with an initial negative test either after 4-5 years in one centre (short interval centre), or 9-10 years in another (long interval centre). The characteristics and incidence rates (IRs) of interval NPCs (defined as cases diagnosed outside the screening protocol while within the screening interval) were compared between these two centres. Standard incidence ratios (SIRs) were also calculated using the general Sihui population as the reference., Results: Seven interval NPCs were detected in the short interval centre (IR: 17.8/10(5) person-years) and 20 in the long interval centre (IR: 20.8/10(5) person-years during the first four years and 43.5/10(5) person-years during the remaining years). The SIR in the short interval centre was 0.43 (95% confidence interval [CI]: 0.17-0.89); SIR in the long interval centre was 0.47 (95% CI: 0.17-1.02) during the first four years and 0.90 (95% CI: 0.49-1.51) during the remaining years. No aggressive interval NPC was observed in the short interval centre; four were identified in the long interval centre., Conclusions: The incidence of NPC, especially aggressive NPC, was low during the first few years after a negative screening; the incidence increased to the general population level afterwards. A screening interval of 4-5 years may therefore be more suitable than 9-10 years after a negative VCA-IgA test in NPC screening.

Background: Elevated levels of antibodies against antigens in the Epstein-Barr virus (EBV) lytic phase are important predictive markers for nasopharyngeal carcinoma (NPC) risk. Several lifestyle factors, including smoking, have also been associated with NPC risk. We hypothesized that some specific lifestyle factors induce transformation of EBV from the latent to the lytic stage and contribute to NPC occurrence., Methods: We conducted a case-control study using data from male case patients (n = 1316) and control subjects (n = 1571) living in Guangdong Province, an area in China at high risk for NPC, to study potential NPC risk factors and EBV inducers. Two independent healthy male populations from a second high-risk area (n = 1657) and a low-risk area (n = 1961) were also included in the analysis of potential EBV inducers using logistic regression models. In vitro assays were performed to investigate the effect of cigarette smoke extract on EBV activation in two EBV-positive cell lines. All statistical tests were two-sided., Results: Smoking was associated with an increased risk of NPC among the Guangdong participants with 20-40 and 40 or more pack-years vs never smokers (OR = 1.52, 95% CI = 1.22 to 1.88 and OR = 1.76, 95% CI = 1.34 to 2.32, respectively; P (trend) < .001). Smoking was the only factor linked to EBV seropositivity among the expanded control group and the independent low-risk population. In vitro experiments showed that cigarette smoke extract promoted EBV replication, induced the expression of the immediate-early transcriptional activators Zta and Rta, and increased transcriptional expression levels of BFRF3 and gp350 in the lytic phase., Conclusion: Smoking is not only associated with NPC risk in individuals from China but is also associated with EBV seropositivity in healthy males and is involved in EBV activation.

Objective: To evaluate the cost-effectiveness of different screening strategies for nasopharyngeal carcinoma (NPC) and recommend a preferable NPC screening strategy., Methods: A Markov simulation model was constructed based on the natural history of NPC. Seven strategies (A. Annual screening; B. Annual screening for (Epstein-Barr virus, EBV) EBV-seropositive subjects, triennial screening for seronegative subjects; C. Biennial screening; D. Triennial screening; E. 4-year screening; F. 5-year screening; G. 6-year screening) were evaluated. The NPC-pickup rate, cost, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated., Results: The ICERs of the 7 strategies were 83 111.6, 47 768.9, 50 164.7, 40 016.2, 34 272.8, 32 215.6, and 32 248.0 Yuan/QALY, respectively. The discounted QALYs of the strategies were 23 079.9, 22 955.6, 22 810.4, 22 636.5, 22 522.7, 22 445.0, and 22 361.9 years, respectively. The ICERs of the strategies were less than three times of the average per capita gross domestic product (89 976 Yuan) in China in 2010. The strategy A achieved a highest NPC pick-up rate (81.7%), a highest discounted QALY and a smallest number of NPC death (681), but a highest discounted cost and a greatest ICER. Compared with the strategy A, the strategy B achieved a little smaller NPC pick-up rate (73.1%), a little smaller number of NPC death (707), however, the ICER of the strategy B decreased by 38.2%., Conclusion: The strategy B (annual screening for EB virus seropositive subjects and triennial screening for seronegative subjects) is a preferable option for NPC screening.

Objective: To explore the incidence regularity in populations with different fluctuation modes of Epstein-Barr virus (EBV) antibody levels., Methods: Based on the data of a NPC mass screening for nasopharyngeal carcinoma (NPC) in Jianggu town and Didou town of Sihui city, Guangdong province from 1992 to 1998, 586 subjects who were positive and retested for twice or above were divided into ascending group (114 subjects), stable or fluctuating group (313 subjects), and descending group (159 subjects) according to the fluctuation of immunoglobulin A antibody against EBV capsid antigen (VCA-IgA) level; 9889 subjects who were negative in the first test of VCA-IgA were set as control group. All the participants were followed-up till December 31, 2007. The incidence, onset time and clinical characteristics of NPC were compared among groups., Results: The 5-year cumulative detection rates of ascending, stable or fluctuating, and descending group were 3.51% (4/114), 0.64% (2/313) and 0.00% (0/159), respectively; the 5-year cumulative detection proportions were 4/4, 2/6 and 0/2, respectively. Comparing to the control group, the hazard ratio (HR) for the incidence of NPC in ascending group was highest (HR = 10.96, 95%CI: 3.91 - 30.74), followed by stable or fluctuating group (HR = 5.79, 95%CI: 2.45 - 13.69), and descending group (HR = 3.84, 95%CI: 0.92 - 16.01) which had the lowest HR., Conclusion: Individuals with stable, fluctuating or ascending VCA-IgA level showed higher risk and earlier onset of NPC was found in ascending group.

Nasopharyngeal carcinoma (NPC) has remarkable epidemiological features, including regional, racial, and familial aggregations. The aim of this review is to describe the epidemiological characteristics of NPC and to propose possible causes for the high incidence patterns in southern China. Since the etiology of NPC is not completely understood, approaches to primary prevention of NPC remain under consideration. This situation highlights the need to conduct secondary prevention, including improving rates of early detection, early diagnosis, and early treatment in NPC patients. Since the 1970's, high-risk populations in southern China have been screened extensively for early detection of NPC using anti-Epstein-Barr virus (EBV) serum biomarkers. This review summarizes several large screening studies that have been conducted in the high-incidence areas of China. Screening markers, high-risk age range for screening, time intervals for blood re-examination, and the effectiveness of these screening studies will be discussed. Conduction of prospective randomized controlled screening trials in southern China can be expected to maximize the cost-effectiveness of early NPC detection screening.

Background and Objective: The Chinese 2008 staging system for nasopharyngeal carcinoma (NPC) was a common set of recommendations by initial revision of the previous'92 staging system. This study was to verify the Chinese 2008 staging system and to provide evidence for its further revision., Methods: Between January 2003 and December 2004, 924 consecutive patients with newly diagnosed, nondisseminated biopsy-proven NPC, presented at the Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, were entered into our study. All patients received magnetic resonance imaging examination of the neck and nasopharynx before treatment. According to the principle of the staging system, the indices of hazard consistency, hazard discrimination, prognostic value, and distribution were used to evaluate the Chinese 2008 staging system., Results: According to the Chinese 2008 staging system, the distribution of stage group for the whole series was 4.9% for the stage I, 22.6% stage II, 38.0% stage III, and 34.5% stage IVA. As for hazard discrimination, the 4-year local relapse-free survival (LRFS) rates for T1-T4 patients were 95.4%, 93.7%, 90.5% and 79.1%, respectively. Although the separation of LRFS for all subclassifications of T-stage showed reasonable, the differences among the subgroups T1, T2, and T3 were still lack of significant statistically. The 4-year distant metastasis failure-free survival (DMFS) rates for N0-N3 patients were 89.4%, 84.3%, 73.6, and 59.2%, respectively. The 4-year overall survival (OS) rates for stage I-IV patients were 96.7%, 94.1%, 82.6% and 67.1%, respectively. As for hazard consistency, the distinctions between T3 with skull base involvement and T3 with medial pterygoid muscle in the hazard ratios of local failure (1.628 vs. 3.905) and disease failure (1.630 vs. 3.288) were large. Multivariate analyses showed that cervical nodal level, extranodal neoplastic spread, and laterality were independent prognostic factors for OS and DMFS, but maximal axial diameter was not., Conclusion: Using the Chinese 2008 staging system for NPC produces an acceptable distribution of patient numbers. Stage group, T classification, and N classification represent independent prognosis factors for major endpoints. However, our study reveals several deficiencies in the current system yet.

Background and Objective: Currently, the serum immunoglobulin A against Epstein-Barr virus capsid antigen (EBV-VCA/IgA) is one of the most commonly used markers for diagnosis of nasopharyngeal carcinoma (NPC). However, its value for prognostic implication in NPC patients is unclear. This study was to evaluate the relationship between pretreatment titers of EBV-VCA/IgA and NPC patients' survival., Methods: The clinicopathologic data of 317 NPC patients treated in Sun Yat-sen University Cancer Center between 1990 and 2003 were retrieved from the registration system of cancer incidence and mortality of Sihui city, Guangdong province. The correlation of pretreatment EBV-VCA/IgA titers to the survival of these patients was analyzed., Results: Pretreatment VCA/IgA titer was significantly higher in stage III-IV NPC patients than in stage I-II patients (p = 0.01). The survival time was significantly shorter in the 170 patients with higher EBV-VCA/IgA titers (>or= 1:160) than in the 147 patients with lower EBV-VCA/IgA titers ( < 1:160). The 5-year survival rate was 65% in low EBV-VCA/IgA titer group and 43% in high titer group (p = 0.01). Multivariate analyses showed that clinical stage, sex, the year of treatment, and pretreatment serum EBV-VCA/IgA titer were all independent prognostic factors of NPC., Conclusion: Pretreatment serum EBV-VCA/IgA titer may be used as an independent prognostic marker of NPC.

Purpose: The aim of the present study was to analyze the expression of Centromere protein H (CENP-H), one of the fundamental components of the human active kinetochore, in nasopharyngeal carcinoma (NPC) and to correlate it with clinicopathologic data, including patient survival., Experimental Design: Using reverse transcription-PCR and Western blot, we detected the expression of CENP-H in normal nasopharyngeal epithelial cells, immortalized nasopharyngeal epithelial cell lines, and NPC cell lines. Using immunohistochemistry, we analyzed CENP-H protein expression in 160 clinicopathologically characterized NPC cases. Statistical analyses were applied to test for prognostic and diagnostic associations., Results: Reverse transcription-PCR and Western blot showed that the expression level of CENP-H was higher in NPC cell lines and in immortalized nasopharyngeal epithelial cells than in the normal nasopharyngeal epithelial cell line at both transcriptional and translational levels. By immunohistochemical analysis, we found that 76 of 160 (47.5%) paraffin-embedded archival NPC biopsies showed high expression of CENP-H. Statistical analysis showed that there was a significant difference of CENP-H expression in patients categorized according to clinical stage (P = 0.024) and T classification (P = 0.027). Patients with higher CENP-H expression had shorter overall survival time, whereas patients with lower CENP-H expression had better survival. A prognostic value of CENP-H was also found of the subgroup of N(0)-N(1) tumor classification. Multivariate analysis showed that CENP-H expression was an independent prognostic indicator for patient's survival., Conclusions: Our results suggest that CENP-H protein is a valuable marker of NPC progression. High CENP-H expression is associated with poor overall survival in NPC patients.

Background & Objective: Few large-scale epidemiologic investigations of nasopharyngeal carcinoma (NPC) at high incidence region in Guangdong province were reported in recent 20 years. This study was to summarize clinical data of a population of hospitalized Cantonese NPC patients,analyze the epidemiologic characteristics of NPC in the high incidence region, and provide references for the prevention and treatment of NPC., Methods: Clinical data of 1 142 Cantonese NPC patients, hospitalized in Cancer Center of Sun Yat-sen University between Jan. 1998 and Aug. 2000, were collected according to well-designed forms and statistically analyzed., Results: The morbidity of NPC in Cantonese showed obvious family clustering: 21.9% of the patients had family history of cancer, and 12.3% had family history of NPC. Moreover, the family clustering feature was more obvious in the population from the region with higher incidence of NPC. The positive rate of VCA/IgA antibody was 90.0%, and that of EA/IgA antibody was 74.5%; the titers were positively related to tumor burden. Early diagnostic rate of NPC was about 30%., Conclusions: NPC patients in Cantonese population have obvious family and territorial clustering. High positive rates of VCA/IgA and EA/IgA antibodies are helpful for early diagnosis of NPC.