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Circulating and disseminated tumour cells in head and neck cancer

Published online by Cambridge University Press:  15 July 2015

A T Harris*
Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, UK Department of Head and Neck Surgery, Aintree University Hospitals NHS Foundation Trust, Liverpool, UK
S Derbyshire
Department of Head and Neck Surgery, Aintree University Hospitals NHS Foundation Trust, Liverpool, UK
J Wilson
Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, UK
C Loh
Department of Head and Neck Surgery, Aintree University Hospitals NHS Foundation Trust, Liverpool, UK
A J Kinshuck
Department of Head and Neck Surgery, Aintree University Hospitals NHS Foundation Trust, Liverpool, UK
B Attlmayr
Department of Head and Neck Surgery, Aintree University Hospitals NHS Foundation Trust, Liverpool, UK
T M Jones
Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, UK Department of Head and Neck Surgery, Aintree University Hospitals NHS Foundation Trust, Liverpool, UK
Address for correspondence: Mr Andrew Harris, North West Cancer Research Centre, 200 London Road, Liverpool L3 9AT, UK E-mail:



Multimodal treatment options in head and neck squamous cell carcinoma have allowed for greater control of locoregional disease, but this has not translated into a significant overall survival advantage for patients. This is partially because these treatment modalities have no influence over the rate of development of distant metastases.


This article summarises the current methods of detecting circulating and disseminated tumour cells. It also discusses how these cells can offer prognostic value in head and neck squamous cell carcinoma, and considers questions posed by the identification of these cells.


A literature search of relevant journal articles was performed using ScienceDirect and PubMed databases, and a general article search was conducted using the online search engine Google.

Results and conclusion:

The evidence presented in this article indicates that circulating tumour cells and disseminated tumour cells may be clinically useful as prognostic markers or in the assessment of response to treatment in head and neck squamous cell carcinoma.

Review Article
Copyright © JLO (1984) Limited 2015 

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1Hauswald, H, Simon, C, Hecht, S, Debus, J, Lindel, K. Long-term outcome and patterns of failure in patients with advanced head and neck cancer. Radiat Oncol 2011;6:70CrossRefGoogle ScholarPubMed
2Allen, CT, Law, JH, Dunn, GP, Uppaluri, R. Emerging insights into head and neck cancer metastasis. Head Neck 2013;35:1669–78CrossRefGoogle ScholarPubMed
3Michiels, S, Le Maître, A, Buyse, M, Burzykowski, T, Maillard, E, Bogaerts, J et al. Surrogate endpoints for overall survival in locally advanced head and neck cancer: meta-analyses of individual patient data. Lancet Oncol 2009;10:341–50CrossRefGoogle ScholarPubMed
4Garavellow, W, Ciardo, A, Spreafico, R, Gaini, R. Risk factors for distant metastases in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2006;132:762–6CrossRefGoogle Scholar
5Joo, YH, Cho, KJ, Park, JO, Nam, IC, Kim, CS, Kim, MS. High-risk human papillomavirus and lymph node size in patients with single node metastasis of oral and oropharyngeal cancer. Acta Otolaryngol 2014;134:395400CrossRefGoogle ScholarPubMed
6Attner, P, Du, J, Näsman, A, Hammarstedt, L, Ramqvist, T, Lindholm, J et al. Human papillomavirus and survival in patients with base of tongue cancer. Int J Cancer 2011;128:2892–7CrossRefGoogle ScholarPubMed
7Näsman, A, Attner, P, Hammarstedt, L, Du, J, Eriksson, M, Giraud, G et al. Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer 2009;125:362–6CrossRefGoogle ScholarPubMed
8Jones, TM. Tumour-infiltrating lymphocytes in the risk stratification of squamous cell carcinoma of the head and neck. Br J Cancer 2014;110:269–70CrossRefGoogle ScholarPubMed
9Huang, SH, Perez-Ordonez, B, Weinreb, I, Hope, A, Massey, C, Waldron, JN et al. Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer. Oral Oncol 2013;49:7985CrossRefGoogle ScholarPubMed
10Fehm, T, Banys, M, Rack, B, Jäger, B, Hartkopf, A, Taran, FA et al. Presence of disseminated tumor cells in bone marrow correlates with tumor stage and nodal involvement in cervical cancer patients. Int J Cancer 2014;134:925–31CrossRefGoogle ScholarPubMed
11Peach, G, Zacharakis, E, Purkayastha, S, Ziprin, P, Kim, C. Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: a systematic review. Br J Cancer 2010;102:1327–34CrossRefGoogle ScholarPubMed
12Schmidt, H, DeAngelis, G, Eltze, E, Gockel, I, Semjonow, A, Brandt, B. Asynchronous growth of prostate cancer is reflected by circulating tumor cells delivered from distinct, even small foci, harboring loss of heterozygosity of the PTEN gene. Cancer Res 2006;66:8959–65CrossRefGoogle ScholarPubMed
13Schindlbeck, C, Andergassen, U, Hofmann, S, Jückstock, J, Jeschke, U, Sommer, H et al. Comparison of circulating tumor cells (CTC) in peripheral blood and disseminated tumor cells in the bone marrow (DTC-BM) of breast cancer patients. J Cancer Res Clin Oncol 2013;139:1055–62CrossRefGoogle ScholarPubMed
14Hristozova, T, Konschak, R, Stromberger, C, Fusi, A, Liu, Z, Weichert, W et al. The presence of circulating tumor cells (CTCs) correlates with lymph node metastasis in nonresectable squamous cell carcinoma of the head and neck region (SCCHN). Ann Oncol 2011;22:1878–85CrossRefGoogle ScholarPubMed
15Langley, RR, Fidler, IJ. The seed and soil hypothesis revisited–the role of tumor-stroma interactions in metastasis to different organs. Int J Cancer 2011;128:2527–35CrossRefGoogle ScholarPubMed
16Möckelmann, N, Laban, S, Pantel, K, Knecht, R. Circulating tumor cells in head and neck cancer: clinical impact in diagnosis and follow-up. Eur Arch Otorhinolaryngol 2014;271:1521CrossRefGoogle ScholarPubMed
17Berois, N, Varangot, M, Aizen, B, Estrugo, R, Zarantonelli, L, Fernández, P et al. Molecular detection of cancer cells in bone marrow and peripheral blood of patients with operable breast cancer. Comparison of CK19, MUC1 and CEA using RT-PCR. Eur J Cancer 2000;36:717–23CrossRefGoogle ScholarPubMed
18Smith, BM, Slade, MJ, English, J, Graham, H, Lüchtenborg, M, Sinnett, HD et al. Response of circulating tumor cells to systemic therapy in patients with metastatic breast cancer: comparison of quantitative polymerase chain reaction and immunocytochemical techniques. J Clin Oncol 2000;18:1432–9CrossRefGoogle ScholarPubMed
19Fehm, T, Braun, S, Muller, V, Janni, W, Gebauer, G, Marth, C et al. A concept for the standardized detection of disseminated tumor cells in bone marrow from patients with primary breast cancer and its clinical implementation. Cancer 2006;107:885–92CrossRefGoogle ScholarPubMed
20Klein, CA. The systemic progression of human cancer: a focus on the individual disseminated cancer cell—the unit of selection. Adv Cancer Res 2003;89:3567CrossRefGoogle Scholar
21Schardt, JA, Meyer, M, Hartmann, CH, Schubert, F, Schmidt-Kittler, O, Fuhrmann, C et al. Genomic analysis of single cytokeratin-positive cells from bone marrow reveals early mutational events in breast cancer. Cancer Cell 2005;8:227–39CrossRefGoogle ScholarPubMed
22Alix-Panabières, C, Riethdorf, S, Pantel, K. Circulating tumor cells and bone marrow micrometastasis. Clin Cancer Res 2008;14:5013–21CrossRefGoogle ScholarPubMed
23Czerkinsky, CC, Nilsson, , Ouchterlony, Ö, Tarkowski, A, Nygren, H. A solid-phase enzyme-linked immunospot (ELISPOT) assay for enumeration of specific antibody-secreting cells. J Immunol Methods 1983;65:109–21CrossRefGoogle ScholarPubMed
24Hampton, R, Walker, M, Marshall, J, Juhl, H. Differential expression of carcinoembryonic antigen (CEA) splice variants in whole blood of colon cancer patients and healthy volunteers: implication for the detection of circulating colon cancer cells. Oncogene 2002;21:7817–23CrossRefGoogle ScholarPubMed
25Cristofanilli, M, Budd, GT, Ellis, MJ, Stopeck, A, Matera, J, Miller, MC et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 2004;351:781–91CrossRefGoogle ScholarPubMed
26Braun, S, Vogl, FD, Naume, B, Janni, W, Osborne, MP, Coombes, RC et al. Pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 2005;353:793802CrossRefGoogle ScholarPubMed
27Colnot, DR, Nieuwenhuis, EJ, Kuik, DJ, Leemans, CR, Dijkstra, J, Snow, GB et al. Clinical significance of micrometastatic cells detected by E48 (Ly-6D) reverse transcription-polymerase chain reaction in bone marrow of head and neck cancer patients. Clin Cancer Res 2004;10:7827–33CrossRefGoogle ScholarPubMed
28Buglione, M, Grisanti, S, Almici, C, Mangoni, M, Polli, C, Consoli, F et al. Circulating tumour cells in locally advanced head and neck cancer: preliminary report about their possible role in predicting response to non-surgical treatment and survival. Eur J Cancer 2012;48:3019–26CrossRefGoogle ScholarPubMed
29Tinhofer, I, Hristozova, T, Stromberger, C, Keilhoiz, U, Budach, V. Monitoring of circulating tumor cells and their expression of EGFR/phospho-EGFR during combined radiotherapy regimens in locally advanced squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 2012;83:e685–90CrossRefGoogle ScholarPubMed
30Camphausen, K, Moses, MA, Beecken, WD, Khan, MK, Folkman, J, O'Reilly, MS. Radiation therapy to a primary tumor accelerates metastatic growth in mice. Cancer Res 2001;61:2207–11Google ScholarPubMed
31Biswas, S, Guix, M, Rinehart, C, Dugger, TC, Chytil, A, Moses, HL et al. Inhibition of TGF-β with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression. J Clin Invest 2007;117:1305–13CrossRefGoogle ScholarPubMed
32Habbous, S, Harland, LT, La Delfa, A, Fadhel, E, Xu, W, Liu, FF et al. Comorbidity and prognosis in head and neck cancers: differences by subsite, stage, and human papillomavirus status. Head Neck 2014;36:802–10CrossRefGoogle ScholarPubMed
33Brockstein, B, Haraf, DJ, Rademaker, AW, Kies, MS, Stenson, KM, Rosen, F et al. Patterns of failure, prognostic factors and survival in locoregionally advanced head and neck cancer treated with concomitant chemoradiotherapy: a 9-year, 337-patient, multi-institutional experience. Ann Oncol 2004;15:1179–86CrossRefGoogle ScholarPubMed
34Freiser, M, Serafini, P, Weed, D. The immune system and head and neck squamous cell carcinoma: from carcinogenesis to new therapeutic opportunities. Immunol Res 2013;57:5269CrossRefGoogle ScholarPubMed