Prospective assessment of a nasopharyngeal carcinoma risk score in a population undergoing screening

Abstract

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.

Environmental Factors for Epstein-Barr Virus Reactivation in a High-Risk Area of Nasopharyngeal Carcinoma: A Population-Based Study

“…In this study population of adults in southern China, where virtually all individuals undergo primary EBV infection in early childhood, elevated VCA/IgA and EBNA1/IgA were implicitly assumed to indicate EBV reactivation, as opposed to primary infection. Study subjects were classified as exhibiting serological evidence of EBV reactivation (Score ≥ 0.65) or not (Score < 0.65) using an EBV-based risk score [ 24 , 25 ]: Score = [e (−3.934 + 2.203 × VCA/IgA + 4.797 × EBNA1/IgA) ]/[1 + e (−3.934 + 2.203 × VCA/IgA + 4.797 × EBNA1/IgA) ]. We also classified study subjects as “low-risk” (Score < 0.65), “medium-risk” (0.65 ≤ Score < 0.98), or “high-risk” (Score ≥ 0.98), using standard cutoffs in the context of NPC screening [ 25 , 26 ].…”

“…Study subjects were classified as exhibiting serological evidence of EBV reactivation (Score ≥ 0.65) or not (Score < 0.65) using an EBV-based risk score [ 24 , 25 ]: Score = [e (−3.934 + 2.203 × VCA/IgA + 4.797 × EBNA1/IgA) ]/[1 + e (−3.934 + 2.203 × VCA/IgA + 4.797 × EBNA1/IgA) ]. We also classified study subjects as “low-risk” (Score < 0.65), “medium-risk” (0.65 ≤ Score < 0.98), or “high-risk” (Score ≥ 0.98), using standard cutoffs in the context of NPC screening [ 25 , 26 ]. The EBV-based risk score based on the combination of VCA/IgA and EBNA1/IgA was previously established under screening scenarios to identify high-risk individuals (ie, EBV seropositive) for NPC in endemic regions [ 24 , 27 ].…”

“…The EBV-based risk score based on the combination of VCA/IgA and EBNA1/IgA was previously established under screening scenarios to identify high-risk individuals (ie, EBV seropositive) for NPC in endemic regions [ 24 , 27 ]. The EBV-based score had a high discriminatory performance (ie, the area under the receiver-operator-characteristic curve was 0.95; 95% confidence interval [CI]= .93–0.97]), which was validated in an ongoing NPC screening trial in southern China with 51 235 adult participants [ 25 ].…”

Effect of EBV Serology-based Screening Program on NPC Mortality: A Cluster Randomized Controlled Trial

“…The design of the screening trial has been described previously 6,16 and is provided in the Study Protocol . Briefly, sixteen towns in two cities (Sihui and Zhongshan) were selected as the cluster randomized units.…”

“…We generated computerized random numbers and selected 8 towns as the screening group (Didou, Jianggu, Longpu, Luoyuan, Weizheng, Xiamao, Jingkou and Xiaolan) and the others (Chengzhong, Dasha, Dongcheng, Huangtian, Shigou, Zhenshan, Nantou and Dongfeng) as the control group. The trial focused on residents aged 30 to 59 in the initial phase ( study protocol Version 1.0 in Study Protocol ) and the eligible age range was broadened in 2012 to additionally include residents aged 60 to 69 years at time of randomization ( study protocol Version 2.0 in Study Protocol ) 16 .…”