An update: circulating tumor cells in head and neck cancer

ABSTRACT

Introduction: Local and distant metastatic disease occurs in approximately half of head and neck squamous cell carcinoma (HNSCC) patients, representing an ongoing cause for treatment failure. Circulating tumor cells (CTCs) are transient cancer cells which have the capacity to metastasize to distant sites such as the lungs and liver in HNSCC. When metastatic disease is radiographically evident, the patient prognosis is often poor. Therefore, methodologies to assess micrometastatic disease are needed to (1) identify patients likely to develop metastatic disease and (2) treat and monitor these patients more aggressively. Whilst CTCs are well documented in other tumor streams such as breast, colorectal cancer and prostate cancers, the data and clinical utility in HNSCC remains limited.

Areas covered: Here we summarize the recent advances of CTCs and applications in HNSCC.

Expert opinion: CTC enumeration can be prognostic in HNSCC; further studies are warranted to investigate the role of CTC clusters in HNSCC; CTC culture (in vivo/ex vivo) may present a possibility to expand these rare cells to a critical mass for functional testing; PD-L1 expression of HNSCC CTCs may present a means by which to determine patients likely to respond to therapy; a HNSCC CTC-specific marker is warranted.

KEYWORDS:

• Head and neck cancers
• circulating tumor cells
• epithelial cell adhesion molecule
• circulating tumor cell microemboli
• programmed death ligand-1

Article highlights

• Circulating tumour cells have shown promise as liquid biopsies in advanced stage head and neck cancers

• Circulating tumour cell threshold/cut-off values need to be established for head and neck cancers

• Beyond enumeration alone, the data on circulating tumour cell clusters, and circulating tumour microemboli is emerging in head and neck cancers.

• Single cell circulating tumour cell characterization is giving insights into CTC heterogeneity

• Expansion of head and neck circulating tumour cells may allow for functional analysis

• Immunotherapeutic biomarkers (e.g. PD-L1) have been identified on head and neck cancer circulating tumour cells.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

The Translational Research Institute is supported by a grant from the Australian Government. This study is supported by the Translational Research Institute Spore grant and Cancer Australia [APP1145657]. NHMRC ECF Fellowship for AK [APP1157741].