Squamous cell carcinoma antigen in hepatocellular carcinoma: Ready for the prime time?

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and the third cause of cancer deaths. The leading predisposing condition is represented by an underlying viral hepatitis, mainly sustained by hepatitis B and C viruses. Since the cumulative risk of developing HCC can be as high as 30-fold in patients with infectious cirrhosis, a timely diagnosis is necessary for establishing an appropriate treatment in these patients. The armamentarium of diagnostic and prognostic biomarkers in patients with HCC currently entails alpha-fetoprotein (AFP) and a limited number of innovative biomarkers, among which squamous cell carcinoma antigen (SCCA) and its immune complexes are among the most widely investigated. The clinical data published so far and reviewed in this article seemingly suggest that neither total serum SSCA or its isoform 1 (i.e., SCCA1) may be ready for the prime time for management of patients with HCC. More interesting evidence has emerged from studies investigating the serum values of SCCA-IgM, since the diagnostic performance of this biomarker was found to be frequently superior to that of AFP and, even more importantly, the combination of SCCA-IgM and AFP was characterized by a much better sensitivity than either biomarker alone, with only a modest decrease of specificity. Larger studies are needed before these preliminary findings can be generalized, but the combined use of AFP and SCCA-IgM represents an appealing perspective in diagnosis and prognostication of HCC.