Hostname: page-component-6766d58669-mzsfj Total loading time: 0 Render date: 2026-05-18T05:06:13.675Z Has data issue: false hasContentIssue false
  • English
  • Français

Genetic profile of head and neck squamous cell carcinoma: clinical implications

Published online by Cambridge University Press:  11 August 2008

F O Agada ,
H Patmore ,
O Alhamarneh ,
N D Stafford  and
J Greenman
F O Agada
Affiliation:
Division of Cancer, Department of Otolaryngology, Head and Neck Surgery, Postgraduate Medical Institute, University of Hull, UK
H Patmore
Affiliation:
Division of Cancer, Department of Otolaryngology, Head and Neck Surgery, Postgraduate Medical Institute, University of Hull, UK
O Alhamarneh
Affiliation:
Division of Cancer, Department of Otolaryngology, Head and Neck Surgery, Postgraduate Medical Institute, University of Hull, UK
N D Stafford
Affiliation:
Division of Cancer, Department of Otolaryngology, Head and Neck Surgery, Postgraduate Medical Institute, University of Hull, UK
J Greenman*
Affiliation:
Division of Cancer, Department of Otolaryngology, Head and Neck Surgery, Postgraduate Medical Institute, University of Hull, UK
*
Address for correspondence: John Greenman, Medical Research Laboratory, University of Hull, Wolfson Building, Cottingham Road, Hull, HU6 7RX, UK. Fax: +44 (0)1482 466996 E-mail: j.greenman@hull.ac.uk
Get access Rights & Permissions [Opens in a new window]

Abstract

The outcome for patients with head and neck squamous cell carcinoma remains poor, despite improvements in diagnosis and treatment over the past three decades. This has triggered great interest in the genetic events that underpin the aetiology and clinical behaviour of this group of cancers. As a result, the genetic profile for head and neck squamous cell carcinomas at different sub-sites has been relatively well characterised at the chromosomal level. Various studies have shown links between specific aberrations in head and neck squamous cell carcinoma and clinical outcome, e.g. loss of heterozygosity at 2q and 18q is commonly associated with poor prognosis, and loss of heterozygosity at 9p21 is associated with recurrence. However, there is as yet no significant clinical application of this genetic knowledge as regards the screening, diagnosis or treatment of head and neck squamous cell carcinoma. Here, we summarise the current state of knowledge, and highlight the most promising areas of research that may facilitate the translation of genetic data into clinical benefit.

Keywords

Head and Neck NeoplasmsSquamous CarcinomaGenetics

Information

Type
Review Article
Information
The Journal of Laryngology & Otology , Volume 123 , Issue 3 , March 2009 , pp. 266 - 272
Copyright
Copyright © JLO (1984) Limited 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

1 Chin, D, Boyle, GM, Porceddu, S, Theile, DR, Parsons, PG, Coman, WB. Head and neck cancer: past, present and future. Expert Rev Anticancer Ther 2006;6:1111–18CrossRefGoogle ScholarPubMed
2 Layland, MK, Sessions, DG, Lenox, J. The influence of lymph node metastasis in the treatment of squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx: N0 versus N+ . Laryngoscope 2005;115:629–39Google Scholar
3 Kowalski, LP. Lymph node metastasis as a prognostic factor in laryngeal cancer. Rev Paul Med 1993;111:42–5Google Scholar
4 Cerezo, L, Millan, I, Torre, A, Aragon, G, Otero, J. Prognostic factors for survival and tumor control in cervical lymph node metastases from head and neck cancer. A multivariate study of 492 cases. Cancer 1992;69:1224–34Google Scholar
5 Rosin, MP, Cheng, X, Poh, C, Lam, WL, Huang, Y, Lovas, J et al. Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia. Clin Cancer Res 2000;6:357–62Google ScholarPubMed
6 El-Naggar, AK, Hurr, K, Huff, V, Clayman, GL, Luna, MA, Batsakis, JG. Microsatellite instability in preinvasive and invasive head and neck squamous carcinoma. Am J Pathol 1996;148:2067–72Google ScholarPubMed
7 Singh, B, Stoffel, A, Gogineni, S, Poluri, A, Pfister, DG, Shaha, AR et al. Amplification of the 3q26.3 locus is associated with progression to invasive cancer and is a negative prognostic factor in head and neck squamous cell carcinomas. Am J Pathol 2002;161:365–71CrossRefGoogle ScholarPubMed
8 Feenstra, M, Veltkamp, M, van Kuik, J, Wiertsema, S, Slootweg, P, van den Tweel, J et al. HLA class I expression and chromosomal deletions at 6p and 15q in head and neck squamous cell carcinomas. Tissue Antigens 1999;54:235–45Google Scholar
9 Lee, DJ, Koch, WM, Yoo, G, Lango, M, Reed, A, Califano, J et al. Impact of chromosome 14q loss on survival in primary head and neck squamous cell carcinoma. Clin Cancer Res 1997;3:501–5Google Scholar
10 Takebayashi, S, Hickson, A, Ogawa, T, Jung, KY, Mineta, H, Ueda, Y et al. Loss of chromosome arm 18q with tumor progression in head and neck squamous cancer. Genes Chromosomes Cancer 2004;41:145–54Google Scholar
11 Califano, J, Westra, WH, Meininger, G, Corio, R, Koch, WM, Sidransky, D. Genetic progression and clonal relationship of recurrent premalignant head and neck lesions. Clin Cancer Res 2000;6:347–52Google Scholar
12 Califano, J, van der Riet, P, Westra, W, Nawroz, H, Clayman, G, Piantadosi, S et al. Genetic progression model for head and neck cancer: implications for field cancerization. Cancer Res 1996;56:2488–92Google ScholarPubMed
13 Pershouse, MA, El-Naggar, AK, Hurr, K, Lin, H, Yung, WK, Steck, PA. Deletion mapping of chromosome 4 in head and neck squamous cell carcinoma. Oncogene 1997;14:369–73Google Scholar
14 Roh, HJ, Shin, DM, Lee, JS, Ro, JY, Tainsky, MA, Hong, WK et al. Visualization of the timing of gene amplification during multistep head and neck tumorigenesis. Cancer Res 2000;60:6496–502Google ScholarPubMed
15 el-Naggar, AK, Hurr, K, Luna, MA, Goepfert, H, Hong, WK, Batsakis, JG. Intratumoral genetic heterogeneity in primary head and neck squamous carcinoma using microsatellite markers. Diagn Mol Pathol 1997;6:305–8Google Scholar
16 Huang, Q, Yu, GP, McCormick, SA, Mo, J, Datta, B, Mahimkar, M et al. Genetic differences detected by comparative genomic hybridization in head and neck squamous cell carcinomas from different tumor sites: construction of oncogenetic trees for tumor progression. Genes Chromosomes Cancer 2002;34:224–33CrossRefGoogle ScholarPubMed
17 Patmore, HS, Ashman, JNE, Cawkwell, L, MacDonald, A, Stafford, ND, Greenman, J. Can a genetic signature for metastatic head and neck squamous cell carcinoma be characterised by comparative genomic hybridisation? Br J Cancer 2004;90:1976–8CrossRefGoogle ScholarPubMed
18 Sparano, A, Quesnelle, KM, Kumar, MS, Wang, Y, Sylvester, AJ, Feldman, M et al. Genome-wide profiling of oral squamous cell carcinoma by array-based comparative genomic hybridization. Laryngoscope 2006;116:735–41Google Scholar
19 Noutomi, Y, Oga, A, Uchida, K, Okafuji, M, Ita, M, Kawauchi, S et al. Comparative genomic hybridization reveals genetic progression of oral squamous cell carcinoma from dysplasia via two different tumourigenic pathways. J Pathol 2006;210:67–74CrossRefGoogle ScholarPubMed
20 Oga, A, Kong, G, Tae, K, Lee, Y, Sasaki, K. Comparative genomic hybridization analysis reveals 3q gain resulting in genetic alteration in 3q in advanced oral squamous cell carcinoma. Cancer Genet Cytogenet 2001;127:24–9Google Scholar
21 Le Tourneau, C, Velten, M, Jung, GM, Bronner, G, Flesch, H, Borel, C. Prognostic indicators for survival in head and neck squamous cell carcinomas: analysis of a series of 621 cases. Head Neck 2005;27:801–8CrossRefGoogle ScholarPubMed
22 Baatenburg de Jong, RJ, Hermans, J, Molenaar, J, Briaire, JJ, le Cessie, S. Prediction of survival in patients with head and neck cancer. Head Neck 2001;23:718–24Google Scholar
23 Verschuur, HP, Irish, JC, O'Sullivan, B, Goh, C, Gullane, PJ, Pintilie, M. A matched control study of treatment outcome in young patients with squamous cell carcinoma of the head and neck. Laryngoscope 1999;109:249–58Google Scholar
24 Soo, KC, Carter, RL, O'Brien, CJ, Barr, L, Bliss, JM, Shaw, HJ. Prognostic implications of perineural spread in squamous carcinomas of the head and neck. Laryngoscope 1986;96:1145–8CrossRefGoogle ScholarPubMed
25 Unal, OF, Ayhan, A, Hosal, AS. Prognostic value of p53 expression and histopathological parameters in squamous cell carcinoma of oral tongue. J Laryngol Otol 1999;113:446–50CrossRefGoogle ScholarPubMed
26 Zatterstrom, UK, Wennerberg, J, Ewers, SB, Willen, R, Attewell, R. Prognostic factors in head and neck cancer: histologic grading, DNA ploidy, and nodal status. Head Neck 1991;13:477–87Google Scholar
27 Janot, F, Klijanienko, J, Russo, A, Mamet, JP, de Braud, F, El-Naggar, AK et al. Prognostic value of clinicopathological parameters in head and neck squamous cell carcinoma: a prospective analysis. Br J Cancer 1996;73:531–8CrossRefGoogle ScholarPubMed
28 Shingaki, S, Suzuki, I, Kobayashi, T, Nakajima, T. Predicting factors for distant metastases in head and neck carcinomas: an analysis of 103 patients with locoregional control. J Oral Maxillofac Surg 1996;54:853–7Google Scholar
29 Bockmühl, U, Schlüns, K, Küchler, I, Petersen, S, Petersen, I. Genetic imbalances with impact on survival in head and neck cancer patients. Am J Pathol 2000;157:369–75Google Scholar
30 Akervall, JA, Jin, Y, Wennerberg, JP, Zätterström, UK, Kjellén, E, Mertens, F et al. Chromosomal abnormalities involving 11q13 are associated with poor prognosis in patients with squamous cell carcinoma of the head and neck. Cancer 1995;76:853–93.0.CO;2-6>CrossRefGoogle ScholarPubMed
31 Meredith, SD, Levine, PA, Burns, JA, Gaffey, MJ, Weiss, LM, Erickson, NL et al. Chromosome 11q13 amplification in head and neck squamous cell carcinoma. Association with poor prognosis. Arch Otolaryngol Head Neck Surg 1995;121:790–4Google Scholar
32 Wreesmann, VB, Wang, D, Goberdhan, A, Prasad, M, Ngai, I, Schnaser, EA et al. Genetic abnormalities associated with nodal metastasis in head and neck cancer. Head Neck 2004;26:10–5Google Scholar
33 Stevens, G, Castle, G, O'Brien, CJ. Treatment of early carcinoma of the vocal cords by radiotherapy. Australas Radiol 1994;38:119–22CrossRefGoogle Scholar
34 Singh, B, Kim, SH, Carew, JF, Yu, I, Shaha, AR, Wolden, S et al. Genome-wide screening for radiation response factors in head and neck cancer. Laryngoscope 2000;110:1251–6CrossRefGoogle ScholarPubMed
35 Nix, P, Cawkwell, L, Patmore, H, Greenman, J, Stafford, N. Bcl-2 expression predicts radiotherapy failure in laryngeal cancer. Br J Cancer 2005;92:2185–9Google Scholar
36 Condon, LT, Ashman, JN, Ell, SR, Stafford, ND, Greenman, J, Cawkwell, L. Overexpression of Bcl-2 in squamous cell carcinoma of the larynx: a marker of radioresistance. Int J Cancer 2002;100:472–5Google Scholar
37 Delfino, V, Casartelli, G, Garzoglio, B, Mereu, P, Bonatti, S, Margarino, G et al. Micronuclei and p53 accumulation in preneoplastic and malignant lesions of the head and neck. Mutagenesis 2002;17:73–7CrossRefGoogle ScholarPubMed
38 Shin, DM, Charuruks, N, Lippman, SM, Lee, JJ, Ro, JY, Hong, WK et al. p53 protein accumulation and genomic instability in head and neck multistep tumorigenesis. Cancer Epidemiol Biomarkers Prev 2001;10:603–9Google Scholar
39 Brown, L, Benchimol, S. The involvement of MAPK signaling pathways in determining the cellular response to p53 activation: cell cycle arrest or apoptosis. J Biol Chem 2006;281:3832–40CrossRefGoogle ScholarPubMed
40 Nikitina, EY, Clark, JI, Van Beynen, J, Chada, S, Virmani, AK, Carbone, DP et al. Dendritic cells transduced with full-length wild-type p53 generate antitumor cytotoxic T lymphocytes from peripheral blood of cancer patients. Clin Cancer Res 2001;7:127–35Google Scholar
41 Hoffmann, TK, Donnenberg, AD, Finkelstein, SD, Donnenberg, VS, Friebe-Hoffmann, U, Myers, EN et al. Frequencies of tetramer+ T cells specific for the wild-type sequence p53 (264–272) peptide in the circulation of patients with head and neck cancer. Cancer Res 2002;62:3521–9Google Scholar
42 Umano, Y, Tsunoda, T, Tanaka, H, Matsuda, K, Yamaue, H, Tanimura, H. Generation of cytotoxic T cell responses to an HLA-A24 restricted epitope peptide derived from wild-type p53. Br J Cancer 2001;84:1052–7Google Scholar
43 Chikamatsu, K, Nakano, K, Storkus, WJ, Appella, E, Lotze, MT, Whiteside, TL et al. Generation of anti-p53 cytotoxic T lymphocytes from human peripheral blood using autologous dendritic cells. Clin Cancer Res 1999;5:1281–8Google Scholar
44 McArdle, SE, Rees, RC, Mulcahy, KA, Saba, J, McIntyre, CA, Murray, AK. Induction of human cytotoxic T lymphocytes that preferentially recognise tumour cells bearing a conformational p53 mutant. Cancer Immunol Immunother 2000;49:417–25Google Scholar
45 Hoffmann, TK, Bier, H, Donnenberg, AD, Whiteside, TL, De Leo, AB. p53 as an immunotherapeutic target in head and neck cancer. Adv Otorhinolaryngol 2005;62:151–60Google Scholar
46 Eura, M, Chikamatsu, K, Katsura, F, Obata, A, Sobao, Y, Takiguchi, M et al. A wild-type sequence p53 peptide presented by HLA-A24 induces cytotoxic T lymphocytes that recognize squamous cell carcinomas of the head and neck. Clin Cancer Res 2000;6:979–86Google ScholarPubMed
47 Asai, T, Storkus, WJ, Mueller-Berghaus, J, Knapp, W, DeLeo, AB, Chikamatsu, K et al. In vitro generated cytolytic T lymphocytes reactive against head and neck cancer recognize multiple epitopes presented by HLA-A2, including peptides derived from the p53 and MDM-2 proteins. Cancer Immun 2002;2:3Google ScholarPubMed
48 van Houten, VM, Leemans, CR, Kummer, JA, Dijkstra, J, Kuik, DJ, van den Brekel, MW et al. Molecular diagnosis of surgical margins and local recurrence in head and neck cancer patients: a prospective study. Clin Cancer Res 2004;10:3614–20CrossRefGoogle Scholar
49 Brennan, JA, Mao, L, Hruban, RH, Boyle, JO, Eby, YJ, Koch, WM et al. Molecular assessment of histopathological staging in squamous-cell carcinoma of the head and neck. N Engl J Med 1995;332:429–35Google Scholar
50 Barrera, JE, Ai, H, Pan, Z, Meyers, AD, Varella-Garcia, M. Malignancy detection by molecular cytogenetics in clinically normal mucosa adjacent to head and neck tumors. Arch Otolaryngol Head Neck Surg 1998;124:847–51Google Scholar
51 Nathan, CA, Amirghahri, N, Rice, C, Abreo, FW, Shi, R, Stucker, FJ. Molecular analysis of surgical margins in head and neck squamous cell carcinoma patients. Laryngoscope 2002;112:2129–40Google Scholar
52 el-Naggar, AK, Hurr, K, Batsakis, JG, Luna, MA, Goepfert, H, Huff, V. Sequential loss of heterozygosity at microsatellite motifs in preinvasive and invasive head and neck squamous carcinoma. Cancer Res 1995;55:2656–9Google ScholarPubMed
53 Stafford, ND. Genetics of Head & Neck Cancer. In: Gleeson, MJ, Jones, NS, Clarke, R, Luxon, L, Hibbert, J, Watkinson, J, eds. Scott-Brown's Otorhinolaryngology: Head & Neck Surgery, 7th edn. 2008: Hodder Arnold, London; 2351–8Google Scholar
54 Chang, SS, Califano, J. Current status of biomarkers in head and neck cancer. J Surg Oncol 2008;97:640–3CrossRefGoogle ScholarPubMed
55 Choi, HR, Roberts, DB, Johnigan, RH, Sturgis, EM, Rosenthal, DI, Weber, RS et al. Molecular and clinicopathologic comparisons of head and neck squamous carcinoma variants: common and distinctive features of biological significance. Am J Surg Pathol 2004;28:1299–310Google Scholar
56 Takebayashi, S, Hickson, A, Ogawa, T, Jung, KY, Mineta, H, Ueda, Y et al. Loss of chromosome arm 18q with tumor progression in head and neck squamous cancer. Genes Chromosomes Cancer 2004;41:145–54Google Scholar
57 Coon, SW, Savera, AT, Zarbo, RJ, Benninger, MS, Chase, GA, Rybicki, BA et al. Prognostic implications of loss of heterozygosity at 8p21 and 9p21 in head and neck squamous cell carcinoma. Int J Cancer 2004;111:206–12CrossRefGoogle ScholarPubMed
58 Yamamoto, N, Mizoe, J, Numasawa, H, Tsujii, H, Shibahara, T, Noma, H. Allelic loss on chromosomes 2q, 3p and 21q: possibly a poor prognostic factor in oral squamous cell carcinoma. Oral Oncol 2003;39:796–805Google Scholar
59 Bockmuhl, U, Ishwad, CS, Ferrell, RE, Gollin, SM. Association of 8p23 deletions with poor survival in head and neck cancer. Otolaryngol Head Neck Surg 2001;124:451–5Google Scholar
60 Shah, SI, Yip, L, Greenberg, B, Califano, JA, Chow, J, Eisenberger, CF et al. Two distinct regions of loss on chromosome arm 4q in primary head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2000;126:1073–6Google Scholar
61 Matsuura, K, Shiga, K, Yokoyama, J, Saijo, S, Miyagi, T, Takasaka, T. Loss of heterozygosity of chromosome 9p21 and 7q31 is correlated with high incidence of recurrent tumor in head and neck squamous cell carcinoma. Anticancer Res 1998;18:453–8Google Scholar
62 Lydiatt, WM, Davidson, BJ, Schantz, SP, Caruana, S, Chaganti, RS. 9p21 deletion correlates with recurrence in head and neck cancer. Head Neck 1998;20:113–18Google Scholar
63 Ransom, DT, Barnett, TC, Bot, J, de Boer, B, Metcalf, C, Davidson, JA et al. Loss of heterozygosity on chromosome 2q: possibly a poor prognostic factor in head and neck cancer. Head Neck 1998;20:404–10Google Scholar
64 Pearlstein, RP, Benninger, MS, Carey, TE, Zarbo, RJ, Torres, FX, Rybicki, BA et al. Loss of 18q predicts poor survival of patients with squamous cell carcinoma of the head and neck. Genes Chromosomes Cancer 1998;21:333–9Google Scholar
65 Lee, DJ, Koch, WM, Yoo, G, Lango, M, Reed, A, Califano, J et al. Impact of chromosome 14q loss on survival in primary head and neck squamous cell carcinoma. Clin Cancer Res 1997;3:501–5Google Scholar
66 Scholnick, SB, Haughey, BH, Sunwoo, JB, el-Mofty, SK, Baty, JD, Piccirillo, JF et al. Chromosome 8 allelic loss and the outcome of patients with squamous cell carcinoma of the supraglottic larynx. J Natl Cancer Inst 1996;88:1676–82Google Scholar
67 Li, X, Lee, NK, Ye, YW, Waber, PG, Schweitzer, C, Cheng, QC et al. Allelic loss at chromosomes 3p, 8p, 13q, and 17p associated with poor prognosis in head and neck cancer. J Natl Cancer Inst 1994;86:1524–9Google Scholar