Comparison of Multi-omics Models for Early Nasopharyngeal Carcinoma Screening: CfDNA Methylation, EBV DNA, and Serological Double-antibodies Detection (PROFOUND-NPC)

Comparison Between Multi-omics Models Including DNA Methylation in CfDNA, Quantitative Determination of Epstein-Barr Virus Nucleic Acid and Serological Double Antibody Detection in Early Screening of Nasopharyngeal Carcinoma

This study focus on nasopharyngeal carcinoma, a cancer type with Chinese characteristics, analyze the early screening detection performance of nasopharyngeal carcinoma in the multi-cancer early screening model, and compare the performance differences among multi-omics models such as nasopharyngeal carcinoma-specific DNA methylation and fragmentome in the multi-cancer early screening model and the clinically routinely conducted Epstein-Barr virus (EBV) nucleic acid quantification (EBV DNA) test and serological double antibody (double antibodies of EBNA1-IgA and VCA-IgA) test. It suggests that compared with EBV DNA quantification and double antibody tests, in patients with nasopharyngeal carcinoma, multi-omics models such as DNA methylation can avoid false negatives, improve sensitivity, and increase the detection rate of early-stage nasopharyngeal carcinoma; in patients without nasopharyngeal carcinoma, multi-omics models such as DNA methylation can avoid false positives, improve specificity, and avoid unnecessary over-diagnosis.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma (NPC)

• Study Type: Observational
• Enrollment (Estimated): 700

Contacts and Locations

• Study Contact: Name: WeiPing Wen; Phone Number: +86 13802966937; Email: wenwp@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • The First Affiliated Hospital of Sun Yat-sen University
      • Contact: YiHui Wen; Phone Number: +86 134 8020 0660; Email: wenyihui@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Confirmed cancers or individuals without confirmed cancer will be invited to participate in this case-control study by a designated consenting professional.

Description

Inclusion Criteria for Case Arm Participants:

1. 40-74 years old
2. Clinically and/or pathologically diagnosed cancer
3. No prior or undergoing any systemic or local antitumor therapy, including but not limited to surgical resection, radiochemotherapy, endocrinotherapy, targeted therapy, immunotherapy, interventional therapy, etc.
4. Able to provide a written informed consent and willing to comply with all part of the protocol procedures

Exclusion Criteria for Case Arm Participants:

1. Pregnancy or lactating women
2. Known prior or current diagnosis of other types of malignancies comorbidities
3. Severe acute infection (e.g. severe or critical COVID-19, sepsis, etc.) or febrile illness (body temperature of ≥ 38.5 °C) within 14 days prior to screen
4. Recipients of organ transplant or prior bone marrow transplant or stem cell transplant
5. Recipients of blood transfusion within 30 days prior to screen
6. Recipients of therapy in past 14 days prior to screen, including oral or IV antibiotics, glucocorticoid, azacitidine, decitabine, procainamide, hydrazine, arsenic trioxide
7. Unsuitable for this trial determined by the researchers

Inclusion Criteria for Control Arm Participants:

1. 40-74 years old
2. Without confirmed cancer diagnosis
3. Able to provide a written informed consent and willing to comply with all part of the protocol procedures

Exclusion Criteria for Control Arm Participants:

1. Pregnancy or lactating women
2. Known prior or current diagnosis of other types of malignancies comorbidities
3. Severe acute infection (e.g. severe or critical COVID-19, sepsis, etc.) or febrile illness (body temperature of ≥ 38.5 °C) within 14 days prior to screen
4. Recipients of organ transplant or prior bone marrow transplant or stem cell transplant
5. Recipients of blood transfusion within 30 days prior to screen
6. Recipients of therapy in the past 14 days prior to screen, including oral or IV antibiotics, glucocorticoid, azacitidine, decitabine, procainamide, hydrazine, arsenic trioxide
7. Unsuitable for this trial determined by the researchers

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Control arm; Participants without a cancer diagnosis after routine cancer screening tests.
Case arm; Participants with newly diagnosed cancer of nasopharyngeal carcinoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
False positive rate and false negative rate of ctDNA Methylation model, EBV DNA quantification test, double antibodies of EBNA1-IgA and VCA-IgA test	To analyze the early screening detection performance of nasopharyngeal carcinoma in the multi-cancer early screening model, and compare the false positive rate and false negative rate among in the multi-cancer early screening model and the clinically routinely conducted Epstein-Barr virus (EBV) nucleic acid quantification (EBV DNA) test and serological double antibody (double antibodies of EBNA1-IgA and VCA-IgA) test.	2 year
Sensitivity and specificity of ctDNA Methylation model, EBV DNA quantification test, double antibodies of EBNA1-IgA and VCA-IgA test in the Screening of nasopharyngeal carcinoma	To analyze the early screening detection performance of nasopharyngeal carcinoma in the multi-cancer early screening model, and compare the sensitivity and specificity among in the multi-cancer early screening model and the clinically routinely conducted Epstein-Barr virus (EBV) nucleic acid quantification (EBV DNA) test and serological double antibody (double antibodies of EBNA1-IgA and VCA-IgA) test.	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and specificity of ctDNA Methylation model, EBV DNA quantification test, double antibodies of EBNA1-IgA and VCA-IgA test in the detection of early-stage nasopharyngeal carcinoma	To analyze the early screening detection performance of nasopharyngeal carcinoma in the multi-cancer early screening model, and compare the sensitivity and specificity among in the multi-cancer early screening model and the clinically routinely conducted Epstein-Barr virus (EBV) nucleic acid quantification (EBV DNA) test and serological double antibody (double antibodies of EBNA1-IgA and VCA-IgA) test in the detection of stage I/II nasopharyngeal carcinoma.	2 year
Modeled positive and negative predictive values of ctDNA Methylation model, EBV DNA quantification test, double antibodies of EBNA1-IgA and VCA-IgA test	The difference in positive and negative predictive values was calculated combined with the incidence of nasopharyngeal carcinoma and compared among in the multi-cancer early screening model and the clinically routinely conducted Epstein-Barr virus (EBV) nucleic acid quantification (EBV DNA) test and serological double antibody (double antibodies of EBNA1-IgA and VCA-IgA) test.	2 year

Collaborators and Investigators

• Sponsor: First Affiliated Hospital, Sun Yat-Sen University
• Collaborators: Xiangya Hospital of Central South University; First Affiliated Hospital of Fujian Medical University; Sixth Affiliated Hospital, Sun Yat-sen University; Fifth Affiliated Hospital, Sun Yat-Sen University; First People's Hospital of Foshan; Zhongshan People's Hospital, Guangdong, China; People's Hospital of Guangxi; Hainan People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 25, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: December 21, 2024
• First Submitted That Met QC Criteria: January 2, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 2, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: cell-free DNA; methylation; cancer early detection
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Carcinoma
• Other Study ID Numbers: PROFOUND-NPC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No