Cluster Randomized Controlled Screening Trial for NPC

Study Overview
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Brief Summary
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This study is aimed to estimate the effectiveness of an Epstein-Barr virus (EBV) serology-based screening program to reduce nasopharyngeal carcinoma (NPC) mortality in a cluster randomized controlled trial in an NPC high-risk population. Sixteen towns in Sihui and Zhongshan Cities, China will be selected, with eight allocated to the screening group and eight to the control group. Cantonese residents aged 30-69 years with no history of NPC will be included. Residents in the screening towns will be invited to undergo serum EBV VCA/EBNA1 IgA antibody tests.

Detailed Description
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Nasopharyngeal carcinoma (NPC) has a high prevalence in southern China. Sihui and Zhongshan cities are located along the Pearl River in Guangdong Province, China, and are well known for a high incidence of NPC worldwide. During the last 20 years, Screening for NPC has been demonstrated to increase the early detection rate of NPC in endemic regions. It is well shown that the effect of Epstein-Barr virus (EBV) serological antibodies is elevated several years before NPC diagnosis; therefore, EBV antibodies have been considered screening markers for NPC. However, none of the studies have reported the impact of screening on NPC-specific mortality. This study aims to launch a cluster-randomized screening trial with combined VCA/IgA and EBNA1/IgA measurement by ELISA as the primary screening method in these 2 cities to examine the impact of EBV serological screening on NPC-specific mortality. Residents aged 30-69 years in eight screening towns in the intervention group will be invited to EBV antibody tests-IgA antibodies to EBV VCA/IgA and EBV nuclear antigen-1 (EBNA1/IgA) by ELISA. The primary objective of this trial is to assess an estimate of the EBV serological antibody-based screening for NPC on NPC-specific in the populations with a high incidence of NPC

Official Title
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A Cluster Randomized Controlled Screening Trial for Nasopharyngeal Carcinoma in Southern China (CRCSTNPC Study)

Conditions
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Nasopharyngeal Cancer, Screening, Morality

Intervention / Treatment
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* Diagnostic Test: Experimental: Screening with EBV VCA/EBNA1-IgA testing


Participation Criteria
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Eligibility Criteria
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Clusters Inclusion criteria 1) the town located in Sihui or Zhongshan city; 2) the town established a tertiary cancer prevention network; 3) the medical staff in the town hospitals agreed to take part in. Exclusion criteria 1) having conducted NPC screening program. Individuals Inclusion criteria 1) being aged 30-69 years; 2) being Cantonese; 3) having signed the informed consent; 4) having an Eastern Cooperative Oncology Group score of 0-2; and 5) having a good physical or psychological condition and consciousness. Exclusion criteria 1) having prevalent NPC.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intervention<br>Residents aged 30-69 years in eight screening towns in the intervention group are invited to screening marker tests - IgA antibodies to EBV VCA/IgA and EBV nuclear antigen-1 (EBNA1/IgA) by ELISA. The trial will use two minimally acceptable false-positive rates (i.e., 10% and 3%) as the cutoffs to define medium-risk (seropositive, 0.65 ≤ score < 0.98) and high-risk participants (seropositive, score ≥ 0.98). After a blood test, participants whose EBV-based risk exceeds the predefined high-risk threshold (score ≥ 0.98) will be referred to endoscopy for clinical evaluation. Participants who are defined as medium-risk or high-risk (score ≥ 0.65) will be followed annually through blood testing and linkage to registers. The remaining participants (seronegative, score < 0.65) will be asked to return for a follow-up visit after five years. | Diagnostic Test: Experimental: Screening with EBV VCA/EBNA1-IgA testing<br>* Participants in the screening towns will be offered screening tests. Those with high-risk scores will be referred to a diagnostic workup examination using fiberoptic endoscopy examination and nasopharyngeal biopsies if suspicious lesions is observed.<br>* Other names: Diagnostic work-up using fiberoptic endoscopy examination and/or nasopharyngeal biopsies;|
| No Intervention: Control<br>The individuals aged 30-69 in the other eight towns will be included as controls, which is a comparable population that will not be screened for NPC. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rate of NPC at 12 years by intervention group | NPC mortality rate will be compared between screening group and control group at 12-year follow-up. | December, 2019 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality at 12 years by intervention group | All-cause mortality rate will be compared between screening group and control group at 12-year follow-up. | December, 2019 | 
| NPC incidence at 12 years by intervention group | NPC incidence rate will be compared between screening group and control group at 12-year follow-up. | December, 2019 | 
| Stage distribution at diagnosis for NPC patients by intervention group | Stage distribution will be compared between screening group and control group at 12-year follow-up. | December, 2019 | 
| NPC overall survival by cases from the two intervention groups | Survival rate will be compared between screening group and control group at 12-year follow-up. | December, 2019 | 
| Cost-effectiveness | Cost-effectiveness of this screening program will be calculated at 12-year follow-up. | December, 2019 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nasopharyngeal cancer, screening, early detection, mortality, randomized control trial, Epstain-Barr Virus