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Head and neck squamous cell carcinoma in focus

This section considers the characteristic features of head and neck squamous cell carcinoma (HNSCC) and the challenges in its clinical management.

Why is treatment of HNSCC a practical challenge in the clinic?

HNSCC has various aetiologies, giving rise to tumours that differ considerably in their molecular, clinical and biological characteristics.1 There are at least 10 anatomical sub-sites for HNSCC, which can make it difficult to ascertain the extent and nature of a patient’s disease and challenging to treat.2 Sites include the oral cavity, nasopharynx, oropharynx, hypopharynx, larynx, paranasal sinuses, nasal cavity and salivary glands.3

Because of the location of tumours in HNSCC, conventional treatment strategies may have a substantial and long-term impact on normal physiological functions, in particular hindering speech and swallowing, as well as affecting patients’ physical appearance.3,4 Treatment must, therefore, take into account organ preservation, as well as morphological and aesthetic side effects.5 These considerations also make the method of administration, tolerability and the issue of treatment adherence highly relevant in clinical practice in HNSCC. Treatment of individual tumours typically requires a multidisciplinary approach based on histological subtype, staging information, the patient’s overall health status, and swallowing and airway function at baseline.3 As such, there are many different factors that contribute to decisions about disease management in HNSCC.

Finally, there are currently no established biomarkers of response in HNSCC. Research to identify subgroups of patients most likely to respond to different systemic therapies is needed.

What are the current treatment options for HNSCC?

HNSCC treatment may include surgery, radiotherapy and systemic therapy.6 There is virtually no role for debulking surgery; if a complete resection cannot be achieved, the potential effect of surgery on a patient’s health-related quality of life is an important consideration.7

Surgery and radiotherapy

Surgery and/or radiotherapy are the treatments of choice for early-stage disease.8 However, despite recent advances in surgical techniques and in delivery of radiotherapy, up to 50% of locally advanced tumours relapse, usually within 2 years after treatment.3 There are then limited options for salvage surgery or re-irradiation,3 even though the administration of radiation and chemoradiation has been refined to provide organ-sparing treatment regimens.Individual response to radiotherapy is highly dependent on tumour location and characteristics, such as intrinsic radiosensitivity of tumour cells, repopulation and hypoxia.9

Systemic therapy

The standard of care for primary systemic treatment is concurrent cisplatin-based chemoradiation, with alternatives including cetuximab or carboplatin/infusional 5-fluorouracil (5-FU), both with concurrent radiotherapy.10 In patients with nasopharyngeal tumours, primary systemic therapy is cisplatin plus radiotherapy with or without adjuvant cisplatin/5-FU or carboplatin/5-FU.10 For patients with recurrent, unresectable or metastatic non-nasopharyngeal HNSCC, combination treatment with cisplatin or carboplatin, 5-FU and cetuximab, or single-agent treatment with nivolumab, is supported by high-quality evidence.10 A number of other combination and single-agent therapies are also included in guidelines, but based on lower-quality evidence; these include pembrolizumab, afatinib* (both non-nasopharyngeal disease only), docetaxel and methotrexate.10

How common is HNSCC and what does it mean for patients?

HNSCC is the sixth most common cancer in the world, with over 500,000 new cases each year.11 A decline in excessive alcohol and tobacco consumption was associated with a reduction in the incidence of carcinomas located in the hypopharynx and larynx in recent decades.12 However, there has been an increase in the incidence of oropharyngeal squamous cell carcinoma, including in patients who do not drink or smoke; this has been attributed to other aetiological factors, such as human papillomavirus infection (HPV).12 In fact, the annual incidence of HPV-related oropharyngeal cancer could surpass that of cervical cancer by 2020.12

In all head and neck cancers, the 5-year relative survival rate improved from 52.7% to 65.9% between 1982–1986 and 2002–2006.13 However, there has been little improvement since then. Recent statistics from the Surveillance, Epidemiology, and End Results (SEER) programme of the National Cancer Institute, based on data from 2006–2012, indicate that the 5-year survival rate is 64% in patients with oral cavity and pharyngeal cancer and 61% in patients with laryngeal cancer.14 Prognosis for patients with recurrent/metastatic HNSCC is dependent on the HPV characterisation status, with worse long-term survival rates reported in patients with HPV-negative HNSCC.15 In general, the 5‑year overall survival rate for HPV-negative HNSCC is around 50%, but it is higher in patients with HPV-positive disease, reaching up to 80%.6

What are the current biomarkers for HNSCC?

HPV and tumour suppressor protein p16 are established prognostic markers for HPV-related HNSCC, with HPV-positive oropharyngeal squamous cell carcinomas exhibiting higher expression of p16 than HPV-negative tumours.16 Survival of patients with HNSCC is prolonged if tumours are HPV positive and p16 positive, or HPV negative and p16 positive.16 However, there are currently no established biomarkers of response in HNSCC.

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*Afatinib is approved in more than 80 markets including the EU, Japan, Taiwan, and Canada under the brand name GIOTRIF®, in the US under the brand name GILOTRIF® and in India under the brand name Xovoltib®; for the full list please see here. Registration conditions differ internationally; please refer to locally approved prescribing information. Afatinib is being investigated in urothelial carcinoma (UC) and head and neck squamous cell carcinoma (HNSCC) and is not approved for these uses. The efficacy and safety of afatinib in UC and HNSCC have not been established.