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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., (© 2024 UICC.)

Epstein-Barr virus (EBV) is detected in nearly 100% of nonkeratinizing nasopharyngeal carcinoma (NPC) and EBV-based biomarkers are used for NPC screening in endemic regions. Immunoglobulin A (IgA) against EBV nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA), and recently identified anti-BNLF2b antibodies have been shown to be the most effective screening tool; however, the screening efficacy still needs to be improved. This study developed a multiplex serological assay by testing IgA and immunoglobulin G (IgG) antibodies against representative EBV antigens that are highly transcribed in NPC and/or function crucially in viral reactivation, including BALFs, BNLF2a/b, LF1, LF2, and Zta (BZLF1). Among them, BNLF2b-IgG had the best performance distinguishing NPC patients from controls (area under the curve: 0.951, 95% confidence interval [CI]: 0.913-0.990). Antibodies to lytic antigens BALF2 and VCA were significantly higher in advanced-stage than in early-stage tumors; in contrast, antibodies to latent protein EBNA1 and early lytic antigen BNLF2b were not correlated with tumor progression. Accordingly, a novel strategy combining EBNA1-IgA and BNLF2b-IgG was proposed and validated improving the integrated discrimination by 15.8% (95% CI: 9.8%-21.7%, p < .0001) compared with the two-antibody method. Furthermore, we found EBV antibody profile in patients was more complicated compared with that in healthy carriers, in which stronger correlations between antibodies against different phases of antigens were observed. Overall, our serological assay indicated that aberrant latent infection of EBV in nasopharyngeal epithelial cells was probably a key step in NPC initiation, while more lytic protein expression might be involved in NPC progression., (© 2024 UICC.)

A small proportion of individuals infected with Epstein-Barr virus (EBV) develop nasopharyngeal carcinoma (NPC). Timing of initial exposure could alter immunological responses to primary EBV infection and explain variation in cancer risk later in life. We measured early life family structure as a proxy for the timing of primary EBV infection to examine whether earlier age at infection alters NPC risk. We utilized data from 480 NPC cases and 1,291 unaffected siblings from Taiwanese NPC multiplex families (≥ 2 family members with NPC, N = 2,921). Information on birth order within the family was derived from questionnaires. We utilized logistic regression models to examine the association between birth order and NPC, accounting for correlations between relatives. Within these high-risk families, older siblings had an elevated risk of NPC. Compared with being a first-born child, the risk (95% CIs) of NPC associated with a birth order of two, three, four and five or more was 1.00 (0.71, 1.40), 0.88 (0.62, 1.24), 0.74 (0.53, 1.05) and 0.60 (0.43, 0.82), respectively (P for trend = 0.002). We observed no associations between NPC risk and the number of younger siblings or cumulative infant-years exposure. These associations were not modified by underlying genetic predisposition or family size. We observed that early life family structure was important for NPC risk in NPC multiplex families, with older siblings having a greater risk of disease. Future studies focusing on more direct measures of the immune response to EBV in early childhood could elucidate the underlying mechanisms., (© 2016 UICC.)

The cancer of upper aerodigestive tract (UADT) is a common cancers in the world. However, its lifetime risk by consumption of alcohol, betel and cigarettes remain to be elucidated. This study aimed to estimate lifetime risk of distinct UADT cancers and assess their associations with alcohol, betel and cigarette consumption. Three cohorts of 25,611 men were enrolled in 1982-1992 in Taiwan. The history of alcohol, betel and cigarette consumption was enquired through questionnaire interview. Newly developed UADT cancers were ascertained through computerized linkage with national cancer registry profile. Lifetime (30-80 years old) risk and multivariate-adjusted hazard ratio (HRadj) of distinct UADT cancers by alcohol, betel and cigarette consumption were estimated. A total of 269 pathologically confirmed cases of UADT cancers were newly-diagnosed during 472,096 person-years of follow-up. The lifetime risk of UADT cancer was 9.42 and 1.65% for betel chewers and nonchewers, 3.22 and 1.21% for cigarette smokers and nonsmokers and 4.77 and 1.85% for alcohol drinkers and nondrinkers. The HRadj (95% confidence interval) of developing UADT cancer was 3.36 (2.51-4.49), 2.02 (1.43-2.84), 1.90 (1.46-2.49), respectively, for the consumption of betel, cigarette and alcohol. Alcohol, betel and cigarette had different effect on cancers at various anatomical sites of UADT. The cancer risk from the mouth, pharynx, esophagus to larynx increased for alcohol and cigarette consumption, but decreased for betel consumption. Alcohol, betel and cigarette consumption are independent risk predictors for distinct UADT cancers., (© 2014 UICC.)

Genetic and environmental factors have been implicated in the etiology of nasopharyngeal carcinoma (NPC), a tumor known to be closely associated with Epstein-Barr virus (EBV) infection. Studies have reported familial aggregation of NPC and have suggested the possible aggregation of NPC and other cancers. We evaluated familial aggregation of cancer in 358 high-risk families with two or more NPC cases enrolled in a NPC genetics study in Taiwan. Participants were linked to the Taiwan National Cancer Registry to identify incident cancers diagnosed after study enrollment (started in 1996) and before December 31, 2005, or death. In total, 2,870 individuals from the NPC Multiplex Family Study contributed 15,151 person-years over an average of 5.3 years of follow-up. One hundred ten incident cancers were identified. Multiple-primary standardized incidence ratios (MP-SIRs) were computed to evaluate overall cancer risk associated with infectious agents and with other tumors. The overall MP-SIR was 1.3 (95% CI: 1.1-1.6), which was largely explained by an excess in NPC (MP-SIR = 15; 95% CI: 10-23). Exclusion of incident NPC diagnoses led to an overall MP-SIR of 1.0 (95% CI: 0.83-1.3). Similarly, the observed excess risk of cancers associated with infectious agents (MP-SIR = 2.0; 95% CI: 1.5-2.6) was driven by the excess in NPC; exclusion of NPC cases led to a reduced MP-SIR that did not differ from 1.0. Analysis of the largest NPC multiplex family study to date confirms the presence of coaggregation of NPC within families in Taiwan but does not provide evidence for a broader familial syndrome involving NPC and other tumors.

The utility of EBV load as a tumor marker in nasopharyngeal carcinoma (NPC) patients suggests that it might also serve as a screening test for individuals who are at high risk for developing NPC. We previously demonstrated that unaffected individuals from high-risk families had elevated anti-EBV antibody levels compared to community controls. In this study, we measured EBV load using 2 different real-time PCR assays (targeting BamH1W and polymerase gene sequences, respectively) carried out in 2 independent research labs in serum samples from 19 untreated NPC cases, 11 healthy community controls and 100 unaffected individuals from families in which 2 or more individuals were affected with NPC. EBV genomes were detectable in 68% of NPC cases by the EBV BamH1W assay and in 74% by the EBV polymerase assay (kappa = 0.64). Patients with stage III or IV disease had significantly higher EBV load compared to those with stage I or II disease (p = 0.008). EBV DNA was detected in a single community control sample by the EBV BamH1W assay and in none of the samples by the EBV polymerase assay. Only one of 100 unaffected family members tested positive by both assays. An additional 14 were positive by only one of the 2 EBV load assays used and usually in only one of the duplicate wells tested, all with very low viral loads (3-50 copies/ml). In addition, EBV load did not correlate with EBV serology results (anti-VCA, anti-DNase, anti-EBNA-1) among these unaffected family members. In conclusion, our study suggests limited clinical utility of the EBV load test, in its current configuration, to screen individuals from high-risk families. Should a more sensitive or specific molecular assay be developed that is capable of detecting and distinguishing tumor-derived EBV genomes or gene products from true negatives, it could be evaluated as a possible screening tool for asymptomatic and early-stage NPC., (Copyright 2005 Wiley-Liss, Inc.)

Most adults have been infected with EBV. Many studies have indicated that antibodies against specific EBV antigens, particularly IgA antibodies, can be predictive or prognostic of EBV-associated malignancies, such as NPC. We hypothesized that healthy individuals from families with a history of multiple members affected with NPC (who therefore might be genetically susceptible to NPC themselves) might have an EBV antibody profile that is distinct from that seen in healthy individuals from the community at large. To explore this possibility and examine determinants of anti-EBV antibody levels in healthy, high-risk individuals, we evaluated data from 2 parallel studies of NPC in Taiwan, which included 1,229 healthy members of families in which 2 or more individuals were affected with NPC and 320 controls from the community at large. Blood collected from participants was tested for IgA antibodies against EBV VCA and EBNA-1 and for neutralizing antibodies against EBV DNase using standard assays. We observed evidence of familial aggregation of EBV seroreactivity among individuals from high-risk, multiplex NPC families. Anti-VCA IgA and anti-EBNA-1 IgA antibody seroprevalence in unaffected family members of NPC cases was 5-6 times higher than in members of the community (p < 0.01). This elevated seroprevalence among unaffected individuals from high-risk families was observed regardless of the relationship of the unaffected individual to the closest affected relative (siblings, parents, children or spouses). No sociodemographic or environmental factors examined were found to strongly and consistently correlate with elevated seroprevalence, but patterns emerged of increasing seroprevalence among older individuals and among females. Unaffected individuals from high-risk NPC families have elevated anti-EBV IgA antibody titers. The etiologic and clinical implications of this finding remain to be established., (Copyright 2004 Wiley-Liss, Inc.)

In 2017, the World Health Organization (WHO) confirmed a new entity, Epstein Barr virus (EBV) + Diffuse large B cell lymphoma (DLBCL), not otherwise specified (NOS). Traces of EBV transcripts were described in lymphomas, including DLBCL, that were diagnosed as EBV negative by conventional methods. The aim of this study was to detect viral genome by qPCR, as well as LMP1 and EBNA2 transcripts, with a more sensitive method in DLBCL cases from Argentina. Fourteen cases originally considered as EBV negative expressed LMP1 and/or EBNA2 transcripts. In addition, LMP1 and/or EBNA2 transcripts were also observed in bystander cells. However, EBERs+ cells cases by conventional ISH showed higher numbers of cells with LMP1 transcripts and LMP1 protein. In the cases that were EBERS− in tumor cells but with expression of LMP1 and/or EBNA2 transcripts, the viral load was below the limit of detection. This study provides further evidence that EBV could be detected in tumor cells by more sensitive methods. However, higher expression of the most important oncogenic protein, LMP1, as well as increased viral load, are only observed in cases with EBERs+ cells by conventional ISH, suggesting that traces of EBV might not display a key role in DLBCL pathogenesis. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the effectiveness of nasopharyngeal cancer (NPC) screening by comprehensive clinical follow-up and adjunctive Epstein-Barr virus (EBV) testing. In a prospective cohort study, 524 individuals with a first-degree family history of NPC were recruited at a university clinical center in Singapore. The cohort was evaluated at baseline and at 6 monthly intervals, with a complete head and neck examination including nasopharyngeal endoscopy. Blood was taken at baseline and at yearly intervals for EBV Viral Capsid Antigen (VCA) IgA, EBV Early Antigen (EA) IgA serology and serum cell-free EBV DNA. Nasopharyngeal biopsy was performed when any irregularity in the nasopharynx was observed, or when EBV markers were elevated. The mean duration of follow-up was 57.7 months, with an average of 8.6 clinical visits per participant. Five participants (0.96%) were identified to have NPC, giving a prevalence of 199 per 100,000 person-years of screening. Four of the five NPC cases identified had asymptomatic T1 disease, at an earlier stage compared to NPC patients diagnosed in the clinic during the same time period (p = 0.0297). All NPC cases identified had elevated EBV-EA IgA titers ≥1:10, with a specificity of 94.6% and a positive predictive value of 15.2%, outperforming EBV-VCA IgA and serum EBV DNA. Two NPC cases were biopsied only because of elevated EBV serology titers, with increasing EBV-EA IgA titers preceding the diagnosis of NPC. In conclusion, screening for NPC is effective in identifying early-stage disease. Adjunctive EBV-EA IgA testing improved the effectiveness of screening., (© 2019 UICC.)

Multiple myeloma (MM) is a hematological malignancy caused by the clonal expansion of plasma cells. The incidence of MM worldwide is increasing with greater than 140 000 people being diagnosed with MM per year. Whereas 5‐year survival after a diagnosis of MM has improved from 28% in 1975 to 56% in 2012, the disease remains essentially incurable. In this review, we summarize our current understanding of MM including its epidemiology, genetics and biology. We will also provide an overview of MM management that has led to improvements in survival, including recent changes to diagnosis and therapies. Areas of unmet need include the management of patients with high‐risk MM, those with reduced performance status and those refractory to standard therapies. Ongoing research into the biology and early detection of MM as well as the development of novel therapies, such as immunotherapies, has the potential to influence MM practice in the future. [ABSTRACT FROM AUTHOR]

Despite evidence suggesting the utility of Epstein-Barr virus (EBV) markers to stratify individuals with respect to nasopharyngeal carcinoma (NPC) risk in NPC high-risk regions, no validated NPC risk prediction model exists. We aimed to validate an EBVbased NPC risk score in an endemic population undergoing screening for NPC. This prospective study was embedded within an ongoing NPC screening trial in southern China initiated in 2008, with 51 235 adult participants. We assessed the score's discriminatory ability (area under the receiver-operator-characteristics curve, AUC). A new model incorporating the EBV score, sex and family history was developed using logistic regression and internally validated using cross-validation. AUCs were compared. We also calculated absolute NPC risk combining the risk score with population incidence and competing mortality data. A total of 151 NPC cases were detected in 2008 to 2016. The EBV-based score was highly discriminating, with AUC = 0.95 (95% CI = 0.93-0.97). For 90% specificity, the score had 87.4% sensitivity (95% CI = 81.0-92.3%). As specificity increased from 90% to 99%, the positive predictive value increased from 2.4% (95% CI = 1.9-3.0%) to 12.5% (9.9-15.5%). Correspondingly, the number of positive tests per detected NPC case decreased from 272 (95% CI = 255-290) to 50 (41-59). Combining the score with other risk factors (sex, firstdegree family history of NPC) did not improve AUC. Men aged 55 to 59 years with the highest risk profile had the highest 5-year absolute NPC risk of 6.5%. We externally validated the discriminatory accuracy of a previously developed EBV score in a high-risk population. Adding nonviral risk factors did not improve NPC prediction [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) occurring in children and adolescence is extremely rare and till present there is a lack of understanding on their clinicopathological and prognostic features of this rare entity. For our study, data of 196 cases children and adolescents with NPC from the past 18 years at a high‐volume cancer center from South China were retrospectively analyzed. Half of the evaluated NPC patients (83/166, 50.0%) were staged as Stage IVa disease, whereas 1.2% (2/166), 27.7% (46/166), 16.9% (28/166) and 4.2% (7/166) had Stage II, III, IVb and IVc disease, respectively. Serum EBV EA‐IgA ≥1:10 and VCA‐IgA ≥1:40 were found in 67.7% (113/167) and 76.6% (128/167) of the evaluated patients, respectively, whereas 56.8% (84/148) of the patients had plasma EBV DNA ≥1000 copies/mL. Histologically, all tumors were classified as nonkeratinizing squamous cell carcinoma (NK‐SCC). Immunohistochemistrically, the expression of CK (AE1/AE3), P63, CK5/6 and P40 were observed in 100% (88/88), 93.2% (68/73), 84.1% (58/69) and 63.2% (12/19) of the detected cases, respectively. All cases show similar immunophenotype compared to that occurring in adult patients. All evaluated cases (71/71 100%) harbored EBER. Patients with plasma EBV DNA ≥1000 copies/mL and positive serum EBV antibodies had significantly inferior 3‐year OS (88% vs 100%, P =.007) compared to other corresponding groups. The combination of EBV serology and plasma EBV DNA are useful to predict the outcome of patients with NPC in children and adolescents. What's new Nasopharyngeal carcinoma (NPC) is extremely rare in children and adolescents, and the clinicopathological characteristics and prognostic features of pediatric NPC remain largely unknown. In this retrospective study, the authors describe the largest series of NPC in children and adolescents in southern China, the most endemic area of NPC, and reveal that all cases histologically belonged to nonkeratinizing squamous cell carcinoma. Moreover, they provide evidence that the combination of Epstein‐Barr virus (EBV) serology and plasma EBV DNA is useful for predicting patient outcome, with potential clinical applications for risk group stratification and prognostic prediction for pediatric NPC patients. [ABSTRACT FROM AUTHOR]

To provide an up‐to‐date overview of recent trends in mortality from oral and pharyngeal cancer, we analyzed death certification data for 61 countries worldwide provided by the World Health Organization in 2010–2015, and, for selected most populous countries, over the period 1970–2016. For 12 largest countries, we analyzed incidence derived from Cancer Incidence in Five Continents in 1960–2012 for all oral and pharyngeal cancers and by subsites. In 2015, male age‐standardized (world population) death rates per 100,000 were 5.03 in the European Union (EU), 8.33 in the Russian Federation, 2.53 in the United States (USA), and 3.04 in Japan; corresponding rates in women were 1.23, 1.23, 0.82, and 0.76. Male mortality decreased over the last decades in several European countries, with earlier and sharper declines in southern Europe; conversely, mortality was still increasing in a few eastern European countries and the United Kingdom. Mortality in men also decreased in Argentina, Australia, and Hong Kong, while it leveled off over more recent calendar years in Brazil, Japan, Mexico, the Republic of Korea, as well as in Australia and the USA. Female mortality slightly rose in various European countries. Overall incidence trends in the largest countries were broadly consistent with mortality ones, but oropharyngeal cancer incidence rose in many countries. Changes in tobacco and alcohol exposure in men over the last decades likely explain the favorable trends in oral and pharyngeal cancer mortality and incidence observed in selected countries worldwide, while increased human papillomavirus infection is likely responsible for the rise in oropharyngeal cancer incidence. What's new? Trends in oral and pharyngeal cancer incidence and mortality historically have been associated with patterns in alcohol and tobacco use. This study, based on global incidence and death data, shows that specifically in men, over the last few decades, death rates for oral and pharyngeal cancer have continued to decline, mirroring favourable patterns in tobacco and alcohol consumption in various populations. Recent increases in oropharyngeal cancer incidence, however, particularly in Australia and the United States, parallel the rise of human papillomavirus infection in those regions. [ABSTRACT FROM AUTHOR]

The vast majority of head and neck cancers (HNCs) are sporadic squamous cell carcinomas, smoking and heavy drinking being the main risk factors. However, little is known about the possible role of family history and the importance of inherited factors versus shared environment. We used Swedish population-based registries to study the family history of HNC. In order to estimate the risk for family members to get the same cancer, and the risk for cancer-specific death in patients with a family history of HNC compared with patients without a family history, multivariate Cox proportional hazards analyses were performed. A 1.43-fold increased risk for developing HNC in the first-degree relatives (FDRs) of HNC patients [hazard ratio (HR), 1.43; 95% CI, 1.28-1.61] was found, when compared with relatives of healthy controls. In spouses of patients with HNC, the risk for developing any HNC was moderately increased (HR, 1.25; 95% CI, 1.01-1.53), compared with spouses of healthy controls. In addition, a 1.34-fold increased risk for death of HNC was found in HNC patients with a family history of HNC (HR, 1.34; 95% CI, (1.03-1.73) compared with HNC patients without a family history. We found an increased risk for HNC in relatives and spouses of HNC patients, when compared with family members of healthy controls. This suggests that in addition to inherited factors, shared environmental factors have a significant role in the development of the cancer. Family history of HNC was associated with worse survival in a newly diagnosed HNC patient. [ABSTRACT FROM AUTHOR]

The paper continues the series of publications from the International Nuclear Workers Study cohort that comprises 308,297 workers from France, the United Kingdom and the United States, providing 8.2 million person-years of observation from a combined follow-up period (at earliest 1944 to at latest 2005). These workers' external radiation exposures were primarily to photons, resulting in an estimated average career absorbed dose to the colon of 17.4 milligray. The association between cumulative ionizing radiation dose and cancer mortality was evaluated in general relative risk models that describe modification of the excess relative risk (ERR) per gray (Gy) by time since exposure and age at exposure. Methods analogous to a nested-case control study using conditional logistic regression of sampled risks sets were used. Outcomes included: all solid cancers, lung cancer, leukemias excluding chronic lymphocytic, acute myeloid leukemia, chronic myeloid leukemia, multiple myeloma, Hodgkin lymphoma and non-Hodgkin lymphoma. Significant risk heterogeneity was evident in chronic myeloid leukemia with time since exposure, where we observed increased ERR per Gy estimates shortly after exposure (2-10 year) and again later (20-30 years). We observed delayed effects for acute myeloid leukemia although estimates were not statistically significant. Solid cancer excess risk was restricted to exposure at age 35+ years and also diminished for exposure 30 years prior to attained age. Persistent or late effects suggest additional follow-up may inform on lifetime risks. However, cautious interpretation of results is needed due to analytical limitations and a lack of confirmatory results from other studies. [ABSTRACT FROM AUTHOR]

Nasopharyngeal cancer (NPC) incidence varies widely across geographic regions and ethnic groups. We conducted a large-scale migrant cohort study to assess origin and migrant generation as predictors of NPC, controlling for possible confounders. Data on 2.3 million Jewish Israeli adolescents, who underwent a compulsory general health examination at ages 16-19 between the years 1967 and 2011 were linked to the Israel National Cancer Registry to obtain incident NPC up to 2012. Cox proportional hazards were used to model time to event. During 46.5 million person-years of follow-up, 276 incident cases were identified. Origin was a strong independent predictor of NPC with high rates for first generation North African born (adjusted HR 5.52; 95% CI 2.43-12.52; p < 0.000044) and Asian born (adjusted HR 3.79; 95% CI 1.43-10.00; p = 0.007) compared to European-born, adjusted for sex, year of birth, residential socio-economic position, years of education, rural residence, body mass index and height. The magnitude of the associations was similar in the Israeli-born of North African and Asian origin, with these second and third generation immigrants showing elevated HRs (adjusted HR 6.09; 95% CI 2.81-13.20; p = 4.72.10−6 and 3.86; 95% CI 1.77-8.41; p = 0.00067, respectively). These findings suggest a strong genetic predisposition and/or efficient cultural transmission of environmental exposures in the etiology of NPC. [ABSTRACT FROM AUTHOR]

High doses of ionizing radiation are an established cause of childhood leukemia. However, substantial uncertainty remains about the effect of low doses of radiation, including background radiation and potential differences between genetic subgroups of leukemia have rarely been explored. We investigated the effect of the background gamma radiation on childhood leukemia using a nationwide register-based case-control study. For each of the 1,093 cases, three age- and gender matched controls were selected ( N = 3,279). Conditional logistic regression analyses were adjusted for confounding by Down syndrome, birth weight (large for gestational age), and maternal smoking. Complete residential histories and previously collected survey data of the background gamma radiation in Finland were used to assess the exposure of the study subjects to indoor and outdoor gamma radiation. Overall, background gamma radiation showed a non-significant association with the OR of childhood leukemia (OR 1.01, 95% CI 0.97, 1.05 for 10 nSv/h increase in average equivalent dose rate to red bone marrow). In subgroup analyses, age group 2-<7 years displayed a larger effect (OR 1.27, 95% CI 1.01, 1.60 for 1 mSv increase in equivalent cumulative dose to red bone marrow). Suggestive difference in OR by genetic subtype was found. Our results provide further support to the notion that low doses of ionizing radiation increase the risk for childhood leukemia, particularly at age 2-<7 years. Our findings suggest a larger effect of radiation on leukemia with high hyperpdiploidy than other subgroups, but this result requires further confirmation. [ABSTRACT FROM AUTHOR]

Despite evidence suggesting the utility of Epstein-Barr virus (EBV) markers to stratify individuals with respect to nasopharyngeal carcinoma (NPC) risk in NPC high-risk regions, no validated NPC risk prediction model exists. We aimed to validate an EBV-based NPC risk score in an endemic population undergoing screening for NPC. This prospective study was embedded within an ongoing NPC screening trial in southern China initiated in 2008, with 51 235 adult participants. We assessed the score's discriminatory ability (area under the receiver-operator-characteristics curve, AUC). A new model incorporating the EBV score, sex and family history was developed using logistic regression and internally validated using cross-validation. AUCs were compared. We also calculated absolute NPC risk combining the risk score with population incidence and competing mortality data. A total of 151 NPC cases were detected in 2008 to 2016. The EBV-based score was highly discriminating, with AUC = 0.95 (95% CI = 0.93-0.97). For 90% specificity, the score had 87.4% sensitivity (95% CI = 81.0-92.3%). As specificity increased from 90% to 99%, the positive predictive value increased from 2.4% (95% CI = 1.9-3.0%) to 12.5% (9.9-15.5%). Correspondingly, the number of positive tests per detected NPC case decreased from 272 (95% CI = 255-290) to 50 (41-59). Combining the score with other risk factors (sex, first-degree family history of NPC) did not improve AUC. Men aged 55 to 59 years with the highest risk profile had the highest 5-year absolute NPC risk of 6.5%. We externally validated the discriminatory accuracy of a previously developed EBV score in a high-risk population. Adding nonviral risk factors did not improve NPC prediction., (© 2020 UICC.)

Recent studies suggested that human papillomavirus (HPV) is an emerging risk factor of head and neck cancer (HNC), particularly for oropharyngeal cancer. Studies from the West showed a rising trend of HPV-related HNC despite a decrease of the overall HNC incidence. In contrast, the overall HNC incidence in Taiwan has continued to rise. It is not clear whether the incidence trends of HPV-related HNC in Taiwan have a similar pattern to those from countries with an overall decreasing incidence of HNC. This study examined the incidence trends of HPV-related and HPV-unrelated HNC in Taiwan using data from the Taiwan Cancer Registry. Our results showed that the incidence trends of HPV-related and HPV-unrelated HNC in Taiwan both rose during 1995-2009. The incidence of HPV-related HNC (1.3 per 100,000 in 1995 to 3.3 in 2009, annual percentage change (APC) = 6.9, p < 0.0001) rose more rapidly than the incidence of HPV-unrelated HNC (10.4 per 100,000 in 1995 to 21.7 in 2009, APC = 5.0, p < 0.0001). The rising trend of HPV-related HNC was particularly prominent for HNC occurring in tonsil (APC = 8.2, p < 0.0001), in men (APC = 7.5, p < 0.0001), and in those aged between 40 and 50 years (APC = 8.5, p < 0.0001). Although the overall incidence of HNC in Taiwan has continued to increase, the most rapid rise is in the HPV-related HNC. This suggests that similar to the Western world, HPV-related HNC is becoming an important public health issue in Taiwan. [ABSTRACT FROM AUTHOR]

There remains great controversy as to whether mouse mammary tumor virus (MMTV), the etiological agent of mammary cancer in mice, or a closely related human retrovirus, plays a role in the development of breast cancer in humans. On one hand, retroviruses such as human T-cell lymphotropic virus and human immunodeficiency virus (HIV) are known causative agents of cancer (in the case of HIV, albeit, indirectly), but attempts to associate other retroviruses with human cancers have been difficult. A recent, high profile, example has been the postulated involvement of another mouse virus, xenotropic murine leukemia virus-related virus, in human prostate cancer, which is now thought to be due to contamination. Here, we review some of the more recent evidence for and against the involvement of MMTV in human breast cancer and suggest future studies that may allow a definitive answer to this conundrum. [ABSTRACT FROM AUTHOR]

The role of cigarette smoking, alcohol use, family history of cancer and the interaction of cigarettes and family history in the etiology of Nasopharyngeal carcinoma (NPC) in general and within each histologic type are unclear. We conducted a case-control study among 1,044 Han Chinese patients with NPC and 1,095 Han Chinese cancer-free control subjects. Logistic regression was used to analyze the association between histologic type of NPC and cigarette smoking, alcohol drinking and family history. The results indicated that NPC was significantly associated with cigarette smoking [adjusted odds ratio (OR) = 2.97, 95% confidence interval (CI), 2.38-3.70], and the association exhibited a dose-response relationship for intensity, duration, and cumulative consumption of cigarettes ( p < 0.0001 for intensity, duration and cumulative consumption of cigarettes). Positive family history of cancer led to a significant 12-fold elevated risk of NPC (adjusted OR = 12.95, 95% CI, 7.12-23.54) and acted jointly with cigarettes in contributing to NPC risk (adjusted OR = 56.68, 95% CI, 17.25-186.19). The association of NPC risk with cigarettes was stronger for nonkeratinizing carcinoma than for keratinizing squamous cell carcinoma (KSCC), whereas family history was more closely associated with KSCC. NPC risk was not associated with alcohol consumption. Our study demonstrated that cigarette smoking and family history of cancer could serve independently and jointly as risk factors for etiology of NPC and might affect the risk of histology-specific NPC differently. This knowledge may help facilitate comprehension of NPC etiology in general as well as within each histologic type, and thereby improve prevention efforts. [ABSTRACT FROM AUTHOR]