/The symptoms, diagnosis and treatment of head and neck cancer

The symptoms, diagnosis and treatment of head and neck cancer

The symptoms, diagnosis and treatment of head and neck cancer2018-09-17T10:36:46+00:00

Summary

Head and neck cancer covers a large group of cancers that arise in this region of the body. They have a similar appearance down the microscope (they are virtually all squamous carcinomas) and have many similarities in their mode of behaviour and spread. The commonest site of origin is the larynx, followed by the oral cavity (the mouth)

Causes

Although the incidence is falling in the UK, the incidence is still high world wide and the environmental factors that predispose are the main reason for this large geographical variation in incidence.

The most important risk factor is smoking, which dramatically increases the risk of head and neck cancer. If smoking is combined with alcohol, the risk increases further.

Various other environmental factors that have been associated with a higher incidence of head and neck cancer are exposure to chromium and nickel dusts and various leather workers and wood workers have rarely been found to have a higher incidence of cancers of the nose or nasal sinuses.

Nasopharynx cancer, which is a slightly unusual subtype of the squamous carcinomas of this region, is related in its incidence to exposure to salty fish in the diet and Epstein-Barr virus infection. It is more common in the Far East.

Squamous head and neck cancer is more common in males.

More recently, cancers of the oropharynx (the tonsil, back of the tongue, and the palate) have been linked to Human Papilloma Virus infection.

Chewing Paan or Beetle Nut, increases the risk of cancer of the tongue, inner cheek and the gums.

Incidence

Skin cancer on the nose before (left panel) and after (right panel) radiotherapy

The title head and neck cancer refers to a large group of cancers that arise in this region of the body, have a similar appearance down the microscope (they are all squamous carcinomas) and have many similarities in their behaviour and spread.

The commonest site of origin is the larynx, followed by the oral cavity (the mouth) and this is followed by the throat (pharynx – divided in to the postnasal space or nasopharynx, the oropharynx and the lowest region, called the hypopharynx, which inferiorly leads into the oesophagus). Carcinoma of the lip is the least common type.

In the UK, there were about 7500 cases of head and neck cancer in 2004.

Symptoms & diagnosis: Head and neck cancer

The symptoms of cancers of the head and neck depend on where they arise.

Symptoms include:

  • A lump in the neck that does not go down after antibiotics
  • A lump in the mouth or back of the throat
  • An ulcer in the mouth that does not heal
  • A loose tooth
  • A tooth socket that does not heal after the tooth has been removed
  • Dentures that do not fit properly when they used to fit well.
  • Pain on swallowing that does not get better
  • Pain in the ear that does not get better
  • Repeated nose bleeds
  • A chronically blocked nose
  • Double vision
  • Severe headaches
  • Swelling of the cheek
  • Swelling of the front of the face
  • A change in the quality of the voice
  • Deafness

The difficulty is that many of the above symptoms can be caused by problems totally unrelated to cancer. Suspicion is raised if things do not improve.

Diagnosis

CT scan demonstrating the invasion of the orbit by cancer

Tests that are run to define the diagnosis include an endoscopy, when a thin flexible camera is put into the upper part of the throat, via the nose. This allows the doctor to look directly at the inside of the head and neck.

Blood tests and scans of the head and neck are often done. The scans may be all or any of a CT scan, an MRI Scan or and Ultrasound of the neck. The scans help to check where the tumour is and if it has spread.

The diagnosis of head and neck cancer can only be confirmed if, a sample of the lump is removed and then examined under the microscope to look at the cells very closely.

Stages

Radioactive iridium wire implant of the tongue

The ‘stage’ of the cancer defines whether the tumour is localised to the organ, whether it has invaded nearby structures, whether it has spread to the local lymph nodes or whether it has spread to other parts of the body. The treating oncologist needs to know the stage to decide the most suitable treatment.

The information needed to decide the stage is gathered from both clinical examination and scanning. An examination under anaesthetic is often done to obtain the most accurate stage, and to get a biopsy.

The stage is usually classified using a system called the ‘TNM Staging System’, where T stands for tumour, N for ‘nodes’ (ie lymph nodes), and M for ‘metastases’ (ie whether other organs are involved). Each letter is followed by a number that defines the extent of the cancer eg T2N1M0.

The diagnosis is confirmed by taking a sample of the lump or suspicious region, and having this examined under a microscope by a specialist. The biopsy may be taken in the out patient clinic, but usually a full examination of the area is undertaken whilst the patient is under anaesthetic. This allows a much more thorough examination to be done. The biopsy can be taken during this procedure. Other tests that are done include a CT scan and an MRI scan.

Treatment & outcomes: Head and neck cancer

Adenoid cystic carcinoma of the right upper eyelid (upper panel) and its successful treatment by radical radiotherapy (Bottom panel – this picture taken immediately at the end of the radiotherapy programme showing the marked skin reaction

The treatment of head and neck cancer depends on where it is and if or where it has spread to. If the tumour has not spread to other parts of the body it may be possible to cure.

The available treatments for cure are surgery, radiotherapy and chemotherapy. The treatment chosen has to have, a good chance of working, whilst having as little effect on the quality of life after treatment. This is often a difficult balance because some of the surgery needed to cure the tumour may remove an important part for example the voice box or part of the tongue. This has effects on speech and swallowing. The advantage of radiotherapy is that it can destroy the tumour whilst leaving the organ in place so patients are, for example, still able to speak and swallow. However, if the tumour is too large or invades bone or cartilage, radiotherapy does not work so well and surgery may be the only chance of cure.

In general, therefore, if the tumour can be removed by an operation without affecting the patient too much, then an operation is recommended. If the operation will significantly affect the patient’s function, then radiotherapy is recommended. If, however the tumour is advanced, then an operation is the only choice and the after effects are accepted but minimised as much as possible.

Radiotherapy can be given after surgery to minimise the chances of the tumour returning.

It is now known that radiotherapy is more effective if chemotherapy is given at the same time. This adds to the side effects and is not suitable for all patients but usually improves the results of treatment. So, a regime of weekly or three weekly chemotherapy (usually based on cisplatin with or without an accompanying drug such as 5 Fluorouracil) during the radiotherapy is advised for all advanced cases of squamous head and neck cancer.

Research also suggests that the effect of radiotherapy can be improved if a drug called Cetuximab (an external domain eGFR – Epidermal Growth Factor Receptor inhibitor) is given at the same time as the radiotherapy. It is given intravenously weekly during the treatment, with the first treatment being given the week before the radiotherapy starts. Currently, it is generally used if Chemotherapy cannot be given safely but can also be a substitute for chemotheray, when/if the patient develops a marked reaction to radiotherapy – as it does not exacerbate the radiation reactions on the mucosa (the lining of the mouth and respiratory tract and pharynx) as do the platin compounds.

Radiotherapy of the head and neck has a lot of side effects, most of which subside completely 2 to 3 months after the end of the radiotherapy. Some effects may be permanent. One of these is a dry mouth, which occurs if the salivary glands receive a high dose of treatment.  With modern radiotherapy called ‘intensity modulated radiotherapy’ (IMRT), the dose to normal tissues is kept lower, whilst still treating the tumour to a high dose.  This can avoid the problem of a permanent dry mouth for a lot of patients. IMRT may also allow a technically better treatment of the tumour than older radiotherapy methods. In brief, all modern radiotherapy for head and neck cancer should be using IMRT technology.

The treatment of head and neck cancer should be done in specialist centres. This is because the surgery is often complex and requires not only skilled surgeons but also well organised aftercare and rehabilitation. The radiotherapy treatment is also complex and, when combined with chemotherapy, is a tough treatment for patients and so needs specialist expertise.

Cancerous ulcer found on side of tongueWhat happens if the treatment is not successful?

If the cancer relapses after radical radiotherapy, salvage surgery is often an option. If there is a relapses in the neck nodes, but the main tumour is controlled, then cure is possible by an operation on the neck (radical neck dissection). If the tumour returns after an operation and radiotherapy has not been given, then it may be possible to aim for cure with radiotherapy.

If the tumour has spread to other parts of the body, then the aim of treatment is to maintain and maximise the quality of life. This may involve chemotherapy, given intravenously.

All modern chemotherapy is based on platin compounds, backed up by suporting drugs such as 5-flourouracil, gemcitabine, methotrexate and other standard cytotoxic chemotherapy agents. However, the addition of the smart drug: cetuximab may be worthwhile in patients who have not already received this agent.

Immunotherapy has now come of age and the checkpoint inhibitor : Nivolumab has proved to be effective in this disease and it is reasonable to trial this immunotherapy as first line therapy in particularly the elderly or infirm with metastatic head and neck cancer.

What to do when all the foregoing has not controlled the disease?

The first consideration is as to whether the disease is localised relapse, regionalised relapse or metastatic to organs further afield

If localised the the option of radical surgery should be considered. if regionalised and particularly for nodal disease in the neck then local and nodal surgery should be considered.

For metastatic disease, then the chemotherapy options based on platins are best first therapy but older drugs including bleomycin and methotrexate can be active.

It is worth considering getting genomic analysis of the cancer at the time of progression – NGS (Next Generation Sequencing) from a new tissue biopsy or a blood draw for cfDNA (cell-free DNA -derived from the broke down DNA of cancer cells that finds itself into the blood for short periods) to see if there are any actionable mutations – a minority chance but, in the refractory disease situation, always worth considering as there is always a few odd driving mutations that can be driving cancers and are able to be inhibited – (perhaps the best contemporary example is the RET oncogene and salivary gland tumours – a situation that can be dramatically inhibited for therapeutic effect by RET inhibitors, for which LOXO192 is the current most powerful inhibitor)..

The analysis of the cancer genome for a high mutation presence or mismatch repair deficiency (MMR+), backed up by a predictive test of PDL-1 expression demonstrating high expression – all predict for response to immunotherapy and Nivolumab ( a checkpoint inhibitor of the PD1-PDL1 interface – t he interface that ‘tells’ the immune system  attack the cancer and this being blunted by the inhibitors of the pD1 (or PDL1) can be dramatically effective in some cases. .

P N Plowman MD, The Oncology Clinic, 20 Harley Street, London W1G 9PH. (Advanced Genomics).

Screening

Screening for head and neck cancer is not routinely performed as the disease is, overall, rare. However, both doctor and dentist must be vigilant that any unhealing oral ulcer could be an early mouth cancer and other symptoms – such as hoarse voice in a smoker, or difficulty in swallowing – can be the first sign of cancer in the larynx and pharynx regions respectively. Occasionally, a neck node enlargement can be the presenting sign of a cancer in the head and neck region – e.g. nasopharynx cancer.