Breakthrough Liver Cancer Early Screening Study by National Cancer Center and Genetron Health Published in PNAS

On March 12, 2019, VCBeat learned that the Proceedings of the National Academy of Sciences (PNAS) published research findings on early hepatocellular carcinoma screening in a prospective cohort of hepatitis B virus carriers, based on cell-free DNA (cfDNA) and protein biomarkers. This study was conducted collaboratively by Genetron Holdings Limited (Genetron Health) and the National Cancer Center/Cancer Hospital of the Chinese Academy of Medical Sciences. Following rigorous clinical validation, these findings hold promise for application in early screening for liver cancer.

This study employed a proprietary liquid biopsy method, HCCscreen, which combines cfDNA gene mutation analysis with protein biomarkers. It demonstrated excellent performance in the highly challenging population of asymptomatic hepatitis B virus (HBV) carriers. The study screened 331 HBV carriers with normal alpha-fetoprotein (AFP) levels and ultrasound results: 24 samples tested positive. During a 6–8 month follow-up period, four cases of hepatocellular carcinoma (HCC) were identified among these positive cases, all being early-stage tumors smaller than 3 cm. Due to early detection, these tumors were amenable to surgical resection, potentially leading to better prognoses. In contrast, no cases of HCC were observed among the remaining 307 individuals who tested negative during the same follow-up period. In this study cohort, the test achieved 100% sensitivity, 94% specificity, and a 17% positive predictive value.

Among the core technologies employed in the HCCscreen method used in this study, the development of Mutation Capsule was supported by Genetron Holdings Limited. This technology enables precise detection of common hepatocellular carcinoma (HCC) mutations, including cfDNA point mutations, insertions and deletions (indels), and HBV viral integration. The research methodology has since undergone further optimization; in addition to the biomarkers reported in the article, it can now simultaneously detect copy number variations (CNVs) and other types of genetic alterations. The optimized technology has been validated in larger-scale, multi-center sample cohorts, demonstrating a stable sensitivity of over 93% and a specificity exceeding 98%.

Mr. Wang Sizhen, Co-founder and CEO of Genetron Holdings Limited, pointed out: “Remarkable progress has been made abroad in controlling the incidence and mortality rates of certain cancers, such as colorectal cancer in the United States and gastric cancer in Japan, largely attributable to early cancer screening and diagnosis. Therefore, Genetron aims to achieve earlier and faster detection of liver cancer through this breakthrough in innovative early-screening technology. Furthermore, building on its achievements in liver cancer early screening, Genetron will continuously optimize its existing technology platform and extend its application to other cancer types, accelerating the translation of scientific advancements into clinical practice. This will truly enable early detection and early treatment of multiple cancers among high-risk and even general healthy populations, thereby improving the overall health status of the nation.”

This study enables the detection of early-stage liver cancer in asymptomatic hepatitis B virus carriers through blood testing. In addition to the current population, the research team is employing this technology to further optimize screening techniques and methods through a systematic, multicenter, large-scale prospective cohort study.

In recent years, significant progress has been made in research on non-invasive biopsy and early screening for cancer using cfDNA mutations as biomarkers. These efforts have recently been extended to multiple cancer types with promising results. The cancer cases involved in prospective cohort studies are mostly asymptomatic early-stage hepatocellular carcinoma (HCC), while non-cancer individuals may suffer from related clinical and subclinical conditions such as chronic hepatitis or occult cirrhosis. Distinguishing between cancer and non-cancer cases in a prospective cohort is more challenging than differentiating healthy individuals from hospital-diagnosed HCC patients (often detected at advanced stages due to symptoms like jaundice or liver area pain) in retrospective studies. However, the algorithms and classification criteria established in prospective cohorts can more accurately identify early-stage cancers and high-risk populations, potentially yielding better outcomes in practical applications of early cancer screening.

As a pioneer in the field of precision oncology in China, Genetron Holdings Limited adheres to the full-cycle R&D philosophy of “Explore, Discover, Apply, Transform,” providing comprehensive products and services spanning “prevention to treatment” (including risk assessment, early screening, molecular pathological diagnosis, medication guidance, and prognosis monitoring). The company offers end-to-end collaborative solutions “from research to clinical practice” for researchers and healthcare professionals in cancer-related fields.

Genetron Holdings Limited operates dual R&D centers in China and the United States, along with four medical testing laboratories covering a total area of over 10,000 square meters, and has achieved dual accreditation from CAP and CLIA. Genetron also boasts an industry-renowned, multidisciplinary expert team with academic backgrounds spanning cancer genomics, bioinformatics, pharmacology, clinical pathology, and other fields.

Genetron Holdings Limited has established long-term partnerships with world-renowned cancer research centers, collaborated on nearly 100 projects with prestigious medical institutions and research institutes both in China and abroad, led numerous major national and local scientific research programs, and published research findings in authoritative academic journals such as Nature Genetics, PNAS, and Nature Communications. Leveraging its “products + services” business model and a product pipeline encompassing “early screening + diagnosis,” Genetron covers hundreds of research institutions and hospitals across China, has served tens of thousands of cancer patients, and has implemented comprehensive upstream and downstream integration across the industry chain. In the field of diagnosis and treatment, its products and services cover a range of cancers, including lung cancer, liver cancer, colorectal cancer, bladder cancer, breast cancer, gastric cancer, thyroid cancer, and brain tumors. In the area of early cancer screening, Genetron has developed technologies with high sensitivity and specificity that have been rigorously validated in large-scale cohorts, holding significant promise for future application in early cancer detection.

The Cancer Hospital of the Chinese Academy of Medical Sciences, founded in 1958, serves as the host institution for the National Cancer Center. It is also home to the National Clinical Research Center for Cancer, the National Quality Control Center for Standardized Diagnosis and Treatment of Cancer, and the National Drug Clinical Research Center certified by the China Food and Drug Administration. As a national flagship specialized cancer hospital integrating medical care, education, research, and prevention, it conducts comprehensive basic research and clinical diagnosis and treatment of cancer. The hospital ranks among the top in China for multidisciplinary standardized comprehensive treatment of various cancers, with an annual outpatient volume of over 840,000 visits and more than 20,000 surgical procedures per year. The hospital boasts five national key disciplines and three national key clinical specialties. It features a first-class team of experts, including three members of the Chinese Academy of Sciences and four members of the Chinese Academy of Engineering. Many of its experts serve as chairpersons or vice-chairpersons in over 70 national professional academic organizations.

The hospital wields extensive academic influence on the international stage, having successively entered into strategic cooperation agreements with renowned global cancer research and treatment institutions, including the International Agency for Research on Cancer (IARC) of the World Health Organization (WHO), the National Institutes of Health (NIH), the National Cancer Institute (NCI), MD Anderson Cancer Center, Mayo Clinic, the University of California, Los Angeles (UCLA), and Cancer Research UK (CRUK).

*Proceedings of the National Academy of Sciences of the United States of America* (PNAS) is one of the most highly cited, comprehensive multidisciplinary scientific journals in the world, dedicated to publishing high-quality scientific research and papers that have undergone rigorous peer review and approval. PNAS publishes cutting-edge research, science news, commentaries, perspectives, colloquium papers, reviews, and activities of the National Academy of Sciences. The journal covers biology, physics, and social sciences, with a global reach.