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Liver (Hepatocellular) Cancer Screening (PDQ®): Screening - Health Professional Information [NCI] - Evidence of Benefit

Rationale for Screening

The rationale for screening for hepatocellular carcinoma (HCC) is based on the concept that populations at high risk for HCC, such as those with cirrhosis, can be identified. However, 20% to 50% of patients presenting with HCC have previously undiagnosed cirrhosis.[1,2] These patients would not be recruited into a surveillance program if the presence of cirrhosis is used to define a target population.[3] The modalities potentially available for screening include serum alpha-fetoprotein (AFP) and ultrasonography. Abnormal screening results may lead to liver biopsy for diagnosis. Complications of liver biopsy are reported in 0.06% to 0.32% of patients, and typically occur within the first few hours after the biopsy.

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Tumor Markers for the Detection of Hepatocellular Carcinoma

There are four categories of tumor markers that are currently being used or studied for the detection of hepatocellular carcinoma. These include oncofetal antigens and glycoprotein antigens; enzymes and isoenzymes; genes; and cytokines.[4]


Serum AFP, a fetal-specific glycoprotein antigen, is the most widely used tumor marker for detecting patients with HCC. The reported sensitivity of AFP for detecting HCC varies widely in both hepatitis B virus (HBV)-positive and HBV-negative populations, which is attributable to overlap between screening and diagnosis study designs.[3] When AFP is used for screening of high-risk populations, a sensitivity of 39% to 97%, specificity of 76% to 95%, and a positive predictive value (PPV) of 9% to 32% have been reported.[5,6,7,8,9] AFP is not specific for HCC. Titers also rise in acute or chronic hepatitis,[10] in pregnancy, and in the presence of germ cell tumors.

A prospective, 16-year, population-based, observational study of screening for hepatocellular cancer among 1,487 Alaska Natives chronically infected with HBV compared survival among screen-detected HCC patients with a historical comparison group of clinically diagnosed HCC patients.[8] The screening program's target was AFP determination every 6 months. It achieved 97% sensitivity and 95% specificity (excluding pregnant women) for HCC. Such high sensitivity and specificity have not been found for other high-risk groups, such as individuals with cirrhosis.[11,12] Whether screening actually improved survival is not clear.

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