Squamous cell carcinoma antigen (SCC)

SCC Antigen Overview

Squamous Cell Carcinoma Antigen (SCC or SCCA) is a protein belonging to the serpin family of protease inhibitors. It is a glycoprotein with a molecular weight of approximately 42-48 kDa, originally isolated from liver metastases of squamous cell carcinoma of the uterine cervix.

SCC antigen is normally present in the cytoplasm of mature squamous epithelial cells found in various tissues, including the skin, cervix, esophagus, and airways. Elevated levels circulating in the blood can be associated with certain types of cancer, particularly squamous cell carcinomas, making it useful as a tumor marker in specific clinical contexts.

Indications for SCC Testing

The primary clinical use of the SCC antigen test is as a tumor marker for:

• Monitoring the course of disease in patients diagnosed with squamous cell carcinoma.
• Evaluating the effectiveness of therapy for squamous cell carcinoma.
• Detecting recurrence of squamous cell carcinoma after treatment.

It is most commonly used in relation to squamous cell carcinomas arising in the following locations:

• Uterine Cervix
• Lung
• Head and Neck (including nasopharynx, ear/temporal bone, larynx, oral cavity)
• Esophagus
• Skin
• Anal canal

SCC antigen is generally not recommended for initial cancer screening in the general population due to insufficient sensitivity and specificity.

Interpretation of SCC Levels

Interpretation of SCC antigen levels should always be done in conjunction with clinical findings, imaging results, and other diagnostic information.

• Normal Range: The upper limit of normal for SCC antigen in serum is typically around 2.0 ng/mL, although this may vary slightly depending on the laboratory and assay used.
• Elevated Levels in Cancer:
  • Elevated levels are most frequently observed in patients with advanced or recurrent squamous cell carcinoma. Sensitivity varies by cancer type and stage.
  • Reported elevation rates include approximately 85% in advanced cervical SCC, around 60% in head and neck SCC (nasopharynx, ear), and about 31% in squamous cell lung carcinoma.
  • SCC levels often correlate with tumor burden, stage, and prognosis. Higher levels generally indicate a larger tumor mass or more advanced disease.
  • A significant decrease in SCC levels after treatment (surgery, radiation, chemotherapy) suggests a positive response.
  • A subsequent rise in SCC levels during follow-up may indicate tumor recurrence or progression, often preceding clinical or radiological detection.

Factors Affecting SCC Levels

It's important to note that elevated SCC antigen levels are not exclusive to cancer. Increased levels can also be found in various benign conditions, potentially leading to false-positive results if interpreted in isolation. These include:

• Benign Skin Conditions: Such as eczema, psoriasis, pemphigus, and other inflammatory dermatoses.
• Benign Head and Neck Conditions: Including infections or inflammation.
• Benign Lung Diseases: Such as pneumonia, tuberculosis, sarcoidosis, and chronic obstructive pulmonary disease (COPD).
• Renal Failure: Impaired kidney function can lead to decreased clearance and elevated SCC levels (sometimes up to 10 ng/mL or higher).
• Liver Disease: Some patients with benign hepatobiliary conditions may show elevated levels.
• Gynecological Conditions: Benign conditions of the cervix or ovaries.

Limitations and Considerations

• Specificity: SCC is not specific to malignancy and can be elevated in benign conditions, limiting its use for initial diagnosis or screening.
• Sensitivity: Not all squamous cell carcinomas produce elevated SCC levels, especially in early stages. A normal level does not rule out cancer.
• Sample Contamination: Extreme care must be taken during sample collection and handling. SCC is present in skin cells and saliva. Contamination of the blood sample with skin flakes or saliva during phlebotomy or processing can lead to falsely elevated results. Hemolysis (breakdown of red blood cells) can also interfere.
• Monitoring Tool: Its primary value lies in monitoring diagnosed patients over time, where changes in levels are more informative than a single value. Baseline levels should ideally be established before starting treatment.

The SCC Blood Test Procedure

The SCC antigen test is performed on a blood sample obtained via standard venipuncture.

• Preparation: No specific patient preparation (like fasting) is usually required.
• Collection: A phlebotomist will draw blood from a vein, typically in the arm. Careful technique is needed to avoid skin/saliva contamination.
• Processing: The blood sample is processed in the laboratory using specific immunoassays to measure the concentration of SCC antigen.

References

1. National Cancer Institute (NCI). (n.d.). Tumor Markers. NCI Dictionary of Cancer Terms. Retrieved from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/tumor-marker
2. American Cancer Society (ACS). (2023). Tumor Markers. Retrieved from https://www.cancer.org/cancer/diagnosis-staging/tests/tumor-markers.html
3. Mayo Clinic Laboratories. (n.d.). Test ID: SCC - Squamous Cell Carcinoma Antigen (SCC), Serum. Test Catalog. Retrieved from https://www.mayocliniclabs.com/test-catalog/Overview/81183 (Example lab reference)
4. Strajina, V., & Kılıç, S. S. (2020). Squamous Cell Carcinoma Antigen in Head and Neck Cancer. *Advances in Experimental Medicine and Biology*, 1247, 87–98. https://doi.org/10.1007/978-3-030-40192-7_6
5. Seregni, E., Botti, C., & Bombardieri, E. (1997). Biochemical characteristics and clinical applications of squamous cell carcinoma antigen (SCC-Ag). *International Journal of Biological Markers*, 12(2), 63–73.