From Viral Detection to Cancer Prevention The Role of NAT in HBV, HCV and HIV Management
When cancer is mentioned, people often think of genetics, environmental factors or unhealthy lifestyles.
However, what may be less known is that approximately 15%-20% of cancer cases worldwide can be attributed to chronic viral infections. Among these pathogens, HBV and HCV are major viral drivers of Hepatocellular Carcinoma (HCC), while HIV-associated immunodeficiency substantially increases the risk of several AIDS-defining and other malignancies.
Highly accurate and sensitive nucleic acid testing (NAT) serves as a powerful tool against these viruses. It is also critical for reducing the long-term risk of virus-associated cancers through early detection and effective disease management.
01 | HBV: A Leading Viral Cause of Hepatocellular Carcinoma (HCC)
HBV infection represents one of the most important causes of HCC worldwide. In resource limited regions such as Asia and Africa, 60%-80% of HCC cases are directly associated with chronic HBV infection. Globally, there were approximately 870,000 new cases and 760,000 deaths attributable to HBV/HCV-related liver cancer in 2022. Without more robust intervention measures, the global number of liver cancer cases is projected to reach 1.52 million and deaths to rise to 1.37 million by 2050.
HBV DNA can integrate randomly into the chromosomes of host hepatocytes, which provides a persistent basis for disrupting the genomic architecture and transcriptional regulation of hepatocytes. Upon integration, the viral X gene (HBx) is frequently retained, resulting in sustained expression of the HBx protein. By activating pro-proliferative signaling pathways such as NF-κB and AP-1, inhibiting TNF-α and Fas-mediated apoptotic pathways, and directly upregulating telomerase TERT expression, HBx may promote hepatocyte proliferation and contribute to cellular immortalization and hepatocarcinogenesis.
02 | HCV: A Curable Infection with Long-Term Oncogenic Risk
Chronic HCV infection causes persistent inflammatory injury to the liver, progressing gradually to hepatic fibrosis and cirrhosis, and markedly increases the risk of HCC. HCV induces T-cell exhaustion, inhibits the anti-tumor activity of NK cells, and impairs immune surveillance of aberrant hepatocytes. This allows precancerous cells to persist, accumulate genetic and epigenetic alterations, and ultimately promote the initiation and progression of HCC. In recent years, the emergence of direct-acting antivirals (DAAs) has transformed the landscape of HCV treatment and greatly improved viral clearance rates. This advancement is expected to substantially reduce the future incidence of HCV-associated HCC.
03 | HIV: Increasing Cancer Risk Through Progressive Immunodeficiency
HIV does not directly encode oncogenes. Instead, it progressively weakens the immune system by targeting CD4⁺ T lymphocytes, eventually leading to acquired immunodeficiency syndrome (AIDS). This state of immunodeficiency facilitates the persistence or reactivation of oncogenic coinfections and impairs immune surveillance against malignant cells. As a result, people living with HIV (PLHIV) face a substantially higher cancer burden than the general population, including AIDS-defining malignancies such as Kaposi’s sarcoma, non-Hodgkin lymphoma, and cervical cancer.
01 | Qualitative Testing: Detecting Early and Window-Period Infections and Occult HBV Infection
High-sensitivity qualitative NAT directly detects viral nucleic acids, supporting the identification of early or window-period infections, occult HBV infection, and infections with low viral loads.
In settings such as blood donor screening, high-risk population screening, and routine preoperative screening, earlier identification can support timely linkage to appropriate care and antiviral treatment, helping achieve viral suppression where applicable and reduce the long-term risk of virus-associated complications, including cancer.
02 | Quantitative Testing: Guiding Clinical Decision-Making and Dynamic Monitoring of Cancer Risk
Dynamic changes in viral load serve as core indicators for assessing infection status, treatment response, and cancer risk. Quantitative NAT is a cornerstone of virological assessment and treatment monitoring for HBV, HCV, and HIV.
Quantitative HBV DNA is a key parameter in assessing viral replication and informing decisions on antiviral treatment, together with other clinical and laboratory factors.Regular monitoring of viral load during treatment enables accurate assessment of antiviral response and timely detection of virological breakthrough and drug resistance. Sustained suppression of HBV replication is associated with a reduced risk of cirrhosis and HCC, although residual HCC risk may remain, particularly in patients with advanced liver disease.
Quantitative HCV RNA testing is essential for confirming active infection and monitoring treatment response, while genotyping may support treatment selection where clinically indicated. Sustained virologic response, typically assessed by undetectable HCV RNA 12 weeks after completion of therapy (SVR12), is the standard endpoint indicating virologic cure.
For PLHIV, quantitative HIV viral load testing is the core indicator for evaluating antiretroviral therapy (ART) efficacy and confirming viral suppression status. Sustained viral suppression enables immune reconstitution and substantially reduces the risk of related cancers. Meanwhile, PLHIV frequently present with HBV/HCV coinfection; multiplex NAT allows comprehensive assessment of coinfection status, enabling formulation of integrated prevention and management strategies to support integrated management of viral coinfections and help reduce the long-term risk of associated complications, including virus-related cancers.
In the era of precision medicine, HBV DNA, HCV RNA, and HIV RNA testing have evolved from an “optional technology” to a “clinical necessity.” From mechanism to bedside, qualitative and quantitative testing of HBV DNA, HCV RNA, and HIV RNA spans the entire clinical pathway: Across the clinical continuum, qualitative and quantitative testing for HBV DNA, HCV RNA, and HIV RNA supports screening, diagnosis, treatment monitoring, assessment of viral suppression or cure where applicable, and long-term risk evaluation. By accurately reflecting viral replication status, these assays provide clinicians with decision support across the continuum of care—from risk assessment and treatment monitoring to prognostic evaluation and long-term follow-up.
Article Reference:
Li Y, Yu W, Yun J, et al. Virus infections and cancers: from mechanisms to therapeutics. Mol Biomed. 2026 Jul 8;7(1):108. doi: 10.1186/s43556-026-00485-6.
