Skip to main content

Advertisement

SpringerLink
Log in

Clinical implications of biomarkers in head and neck cancer

  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

The term biomarker refers to a host of biologic factors found within a tumor or other clinical specimen that can be used to assess the tumor in some way. Biomarkers have many potential clinical applications. Before they are used in actual clinical settings, however, they must be carefully validated. The literature contains many reports of this ongoing work related to head and neck squamous cell carcinoma. Candidate biomarkers for this disease include the p53 gene and its protein; microsatellite regions throughout the genome; human papillomavirus; proteins involved in cellular proliferation, apoptosis, angiogenesis, and intracellular adhesion; epithelial growth factor receptor; and various measures of immune response to cancer. The best new evidence for the validity of each of these candidates is critiqued in this review.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Ma L, Ronai A, Riede UN, et al.: Clinical implication of screening p53 gene mutations in head and neck squamous cell carcinomas. J Cancer Res Clin Oncol 1998, 124:389–396.

    Article  PubMed  CAS  Google Scholar 

  2. Koch WM, Brennan JA, Zahurak M, et al.: p53 mutation and locoregional treatment failure in head and neck squamous cell carcinoma. J Natl Cancer Inst 1996, 88:1580–1586.

    Article  PubMed  CAS  Google Scholar 

  3. Narayana A, Vaughan ATM, Gunaratne S, et al.: Is p53 an independent prognostic factor in patients with laryngeal carcinoma? Cancer 1998, 82:286–291.

    Article  PubMed  CAS  Google Scholar 

  4. Masuda M, Shinokuma A, Hirakawa N, et al.: Expression of bcl-2, p53 and Ki-67 and outcome of patients with primary nasopharyngeal carcinomas following DNA-damaging treatment. Head Neck 1998, 20:640–644.

    Article  PubMed  CAS  Google Scholar 

  5. Jin YT, Kayser S, Kemp BL, et al.: The prognostic significance of the biomarkers p21WAF1/CIP1, p53 and bcl-2 in laryngeal squamous cell carcinoma. Cancer 1998, 82:2159–2165.

    Article  PubMed  CAS  Google Scholar 

  6. Homma A, Furuta Y, Oridate N, et al.: Prognostic significance of clinical parameters and biological markers in patients with squamous cell carcinoma of the head and neck treated with concurrent chemoradiotherapy. Clin Cancer Res 1999, 5:801–806. This is a large study involving 111 patients treated uniformly. It employs excellent statistical methods. Results show that Bcl-2 expression is associated with better locoregional control, while Ki-67 expression may portend worse overall survival. p53 expression had no value as a prognostic marker.

    PubMed  CAS  Google Scholar 

  7. Lera J, Lara PC, Perez S, et al.: Tumor proliferation, p53 expression, and apoptosis in laryngeal carcinoma: relation to the results of radiotherapy. Cancer 1998, 83:2493–2501.

    Article  PubMed  CAS  Google Scholar 

  8. Giatromanolaki A, Koukourakis M, Zaramboukas T, et al.: p53 and bcl-2 expression in locally advanced squamous cell head-neck cancer treated with platinum based chemotherapy and radiotherapy. Anticancer Res 1998, 18:4685–4692.

    PubMed  CAS  Google Scholar 

  9. Kropveld A, Slootweg PJ, Blankenstein MA, et al.: Ki-67 and p53 in T2 laryngeal cancer. Laryngoscope 1998, 108:1548–1552.

    Article  PubMed  CAS  Google Scholar 

  10. Cruz IB, Snidjer PJF, Meijer CJ, et al.: p53 expression above the basal cell layer in oral mucosa is an early event of malignant transformation and has predictive value for developing oral squamous cell carcinoma. J Pathol 1998, 184:360–368.

    Article  PubMed  CAS  Google Scholar 

  11. Murti PR, Warnakulasuriya KA, Johnson NW, et al.: p53 expression in oral precancer as a marker for malignant potential. J Oral Pathol Med 1998, 27:191–196.

    Article  PubMed  CAS  Google Scholar 

  12. Brennan JA, Mao L, Hruban RH, et al.: Molecular assessment of histopathologic staging in squamous-cell carcinoma of the head and neck. N Engl J Med 1995, 332:429–435.

    Article  PubMed  CAS  Google Scholar 

  13. Ball VA, Righi PD, Tejada E, et al.: p53 immunostaining of surgical margins as a predictor of local recurrence in squamous cell carcinoma of the oral cavity and oropharynx. Ear Nose Throat J 1997, 76:818–823.

    PubMed  CAS  Google Scholar 

  14. Ralhan R, Nath N, Agarwal S, et al.: Circulating p53 antibodies as early markers of oral cancer: correlation with p53 alterations. Clin Cancer Res 1998, 4:2147–2152.

    PubMed  CAS  Google Scholar 

  15. Knudsen AG: Antioncogenes and human cancer. Proc Natl Acad Sci U S A 1993, 90:109–114.

    Article  Google Scholar 

  16. Spafford M, Koch WM, Sidransky D, et al.: Molecular detection of head and neck squamous cell carcinoma in saliva using microsatellite analysis. Otolaryngol Head Neck Surg 1998, 119:P92.

    Google Scholar 

  17. Califano J, Westra W, Koch W, et al.: Unknown primary head and neck squamous cell carcinoma: molecular identification of site of origin. J Natl Cancer Inst 1999, 91:599–604. This is the first publication demonstrating a clinical application of microsatellite alterations as sensitive detection markers. The results suggest both important clinical application for the technology as well as interesting insight into the phenomena of field cancerization and the unknown primary cancer.

    Article  PubMed  CAS  Google Scholar 

  18. Leong P, Rezai B, Koch W, et al.: Clonal relationship of synchronous and metachronous tumor of the head and neck and lung: a genetic approach for distinguishing independent primary tumors and distant metastases. J Natl Cancer Inst 1998, 90:972–977. Microsatellite alterations can be used to link tumors separated by time and space, demonstrating their common clonal origin. This has implications for chemoprevention strategies, and may be useful in decision making for patients with apparent second primary disease.

    Article  PubMed  CAS  Google Scholar 

  19. Califano J, Leong P, Koch W, et al.: Clonal relationship of synchronous and metachronous tumors of the head and neck and esophagus. Clinical Cancer Res 1999, 5:1862–1867.

    CAS  Google Scholar 

  20. Mao L, El-Naggar AK, Papadimitrakopoulou V, et al.: Phenotype and genotype of advanced premalignant head and neck lesions after chemoprentive therapy. J Natl Cancer Inst 1998, 20:1545–1551. Although a preliminary report with small numbers, this publication represents a seminal effort to use biomarkers in an actual clinical trial. The data indicate that the biomarkers may be superior to standard clinical assessment, or at least independently relevant to prediction of clinical outcome.

    Article  Google Scholar 

  21. Lazar AD, Winter MR, Nogueria CP, et al.: Loss of heterozygosity at 11q23 in squamous cell carcinoma of the head and neck is associated with recurrent disease. Clin Cancer Res 1998, 4:2787–2793.

    PubMed  CAS  Google Scholar 

  22. Gillison ML, Capone RB, Koch WM, et al.: A subset of head and neck squamous cell carcinomas (HNSCC) is linked to Human Papillomavirus HPV) infection [abstract]. Proc ASCO 1999, 18:389a.

    Google Scholar 

  23. Capone R, Gillison M, Nawroz H, et al.: A serum assay for human papillomavirus DNA is negative in a group of HNSCC patients [abstract]. Proc ASCO 1999, 40:41.

    Google Scholar 

  24. Liu SC, Sauter ER, Clapper ML, et al.: Markers of cell poliferation in normal epithelia and dysplastic leukoplakias of the oral cavity. Cancer Epidem, Biomarkers Prevent 1998, 7:597–603.

    CAS  Google Scholar 

  25. Pignataro L, Capaccio P, Pruneri G, et al.: The predictive value of p53, MDM-2, cyclin D1 and Ki-67 in the progression from low-grade dysplasia towards carcinoma of the larynx. J Laryngol Otol 1998, 112:455–459.

    PubMed  CAS  Google Scholar 

  26. Staibano S, Mignogna MD, Muzio LL, et al.: Overexpression of Cyclin-D1, bcl-2, and bax proteins, proliferating cell nuclear antigen (PCNA) and DNA-ploidy in squamous cell carcinoma of the oral cavity. Human Pathol 1998, 29:1189–1194.

    Article  CAS  Google Scholar 

  27. Sarac S, Ayhan A, Hosal AS, et al.: Prognostic significance of PCNA expression in laryngeal cancer. Arch Otolaryngol Head Neck Surg 1998, 124:1321–1324.

    PubMed  CAS  Google Scholar 

  28. Krecicki T, Jelen M: Proliferating cell nuclear antigen in laryngeal cancer. J Laryngol Otol 1998, 112:310–313.

    PubMed  CAS  Google Scholar 

  29. Nishimura G, Tsukuda M, Zhou LX, et al.: Cyclin D1 expression as a prognostic factor in advanced hypopharyngeal carcinoma. J Laryngol Otol 1998, 112:552–555.

    PubMed  CAS  Google Scholar 

  30. Costa A, Licitra L, Veneroni S, et al.: Biological markers as indicators of pathological response to primary chemotherapy in oral-cavity cancers. Int J Cancer 1998, 79:619–623.

    Article  PubMed  CAS  Google Scholar 

  31. Drenning SD, Marcovitch AJ, Johnson DE, et al.: Bcl-2 but not bax is associated with apoptosis in normal and transformed squamous epithelium. Clin Cancer Res 1998, 4:2913–2921.

    PubMed  CAS  Google Scholar 

  32. Xie X, Clausen OPF, De Angelis P, et al.: Bax expression has prognostic significance that is enhanced when combined with AgNOR counts in glottic carcinomas. Br J Cancer 1998, 78:100–105.

    PubMed  CAS  Google Scholar 

  33. Sauter ER, Nesbit M, Watson JC, et al.: Vascular endothelial growth factor is a marker of tumor invasion and metastasis in squamous cell carcinomas of the head and neck. Cancer Res 1999, 5:775–782.

    CAS  Google Scholar 

  34. Maeda T, Matsumura S, Hiranuma H, et al.: Expression of vascular endothelial growth factor in human oral squamous cell carcinoma: its association with tumor progression and p53 gene status. J Clin Path 1998, 51:771–775.

    PubMed  CAS  Google Scholar 

  35. Giatromanolaki A, Koukourakis MI, Georgoulias V, et al.: Angiogenesis vs. response after combined chemoradiotherapy of squamous cell head and neck cancer. Int J Cancer 1999, 80:810–817.

    Article  PubMed  CAS  Google Scholar 

  36. Grandis JR, Melhem MF, Gooding WE, et al.: Levels of TGF-and EGFR protein in head and neck squamous cell carcinoma and patient survival. J Natl Cancer Inst 1998, 90:824–832. This is one of the better reports, examining a single prognostic biomarker candidate with strong hypothetical rationale, excellent statistical methods, and adequate sample size. The results indicate no strong advantage of EGFR or its ligand as a marker, both being predictive of outcome with equal certainty. The study is of particular interest because EGFR is a target of novel therapeutic approaches using monoclonal antibodies in conjunction with standard chemotherapy in ongoing clinical trials.

    Article  Google Scholar 

  37. Guerry M, Vabre L, Talbot M, et al.: Prognostic value of histological and biological markers in pharyngeal squamous cell carcinoma: a case-control study. Br J Cancer 1998, 77:1932–1936.

    PubMed  CAS  Google Scholar 

  38. Reichert TE, Day R, Wagner EM, et al.: Absent or low expression of the z chain in T cells at the tumor site correlates with poor survival in patients with oral carcinoma. Cancer Res 1998, 58:5344–5347.

    PubMed  CAS  Google Scholar 

  39. Murr C, Berchtold J, Norer B, et al.: Neopterin as a prognostic parameter in patients with squamous cell carcinomas of the oral cavity. Int J Cancer 1998, 79:476–480.

    Article  PubMed  CAS  Google Scholar 

  40. Gottschlich S, Gorogh T, Lippert BM, et al.: The soluble interleukin-2 receptor - a marker for squamous cell carcinoma of the upper aerodigestive tract. Anticancer Res 1997, 17:2921–2922.

    PubMed  CAS  Google Scholar 

  41. Wu LJ, Chen KY, Chi KH, et al.: The significance of soluble interleukin-2 receptor in monitoring disease relapse in patients with nasopharyngeal cancer. Jpn J Clin Oncol 1998, 28:729–732.

    Article  PubMed  CAS  Google Scholar 

  42. Shinohara M, Hiraki A, Ikebe T, et al.: Immunohistochemical study of desmosomes in oral squamous cell carcinoma: correlation with cytokeratin and E-cadherin staining, and with tumor behavior. J Pathol 1998, 184:369–381.

    Article  PubMed  CAS  Google Scholar 

  43. Klaassen I, Copper MP, Brakenhoff RH, et al.: Exfoliated oral cell messenger RNA: suitability for biomarker studies. Cancer Epidemiol Biomarkers Prevent 1998, 7:469–472.

    CAS  Google Scholar 

  44. Sumida T, Hamakawa H, Sogawa K, et al.: Telomerase components as a diagnostic tool in human oral lesions. Int J Cancer 1999, 80:1–4.

    Article  PubMed  CAS  Google Scholar 

  45. Barrera JE, Ai H, Pan Z, et al.: Malignancy detection by molecular cytogenetics in clinically normal mucosa adjacent to head and neck tumors. Arch Otolaryngol Head Neck Surg 1998, 124:847–851.

    PubMed  CAS  Google Scholar 

  46. Omura K, Nagasato A, Kanehira E, et al.: Retinoblastoma protein and proliferating cell nuclear antigen expression as predictors of recurrence in well-differentiated papillary thyroid carcinoma. J Clin Oncol 1997, 15:3458–3463.

    PubMed  CAS  Google Scholar 

  47. Wollenberg B, Jan N, Sautier W, et al.: Serum levels of intercellular adhesion molecule-1 in squamous cell carcinoma of the head and neck. Tumour Biol 1997, 18:88–94.

    Article  PubMed  CAS  Google Scholar 

  48. Liu CM, Sheen TS, Ko JY, et al.: Circulating intercellular adhesion molecule 1 (ICAM-1), E selectin and vascular cell adhesion molecule 1 (VCAM-1) in head and neck cancer. Br. J Cancer 1999, 79:360–362.

    Article  PubMed  CAS  Google Scholar 

  49. Krimmel M, Hoffmann J, Krimmel C, et al.: Relevance of SCC-ag, CEA, CA 19.9 and CA 125 for diagnosis and followup in oral cancer. J Cranioaxillofac Surg 1998, 26:243–248.

    CAS  Google Scholar 

  50. Lin WY, Yen TC, Cheng KY, et al.: The value of CYFRA 21-1, a new tumor marker, in nasopharyngeal carcinoma. Neoplasma 1998, 45:21–24.

    PubMed  CAS  Google Scholar 

  51. Khan A, Baker SP, Patwardhan NA, et al.: CD57 (Leu-7) expression is helpful in diagnosis of the follicular variant of papillary thyroid carcinoma. Virchows Arch 1998, 432:427–432. If CD57 is confirmed as highly specific for follicular carcinoma, and not present in adenomas, it will have immediate and valuable application as a biomarker. Multicenter prospective trials should be initiated.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery and Oncology, Johns Hopkins University School of Medicine, 601 North Caroline Street, 21287-0910, Baltimore, MD, USA

    Wayne M. Koch MD

Authors
  1. Wayne M. Koch MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koch, W.M. Clinical implications of biomarkers in head and neck cancer. Curr Oncol Rep 1, 129–137 (1999). https://doi.org/10.1007/s11912-999-0023-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11912-999-0023-5

Keywords

Search

Navigation