Head and Neck Cancer

Introduction

Fig. 1 – The anatomical relationship of the pharynx, nasal cavity, and oral cavity

Head and neck cancer refers to malignancies of the oral cavity, pharynx, larynx, paranasal sinuses, nasal cavity or salivary glands. Over 90% derive from squamous cell epithelium, hence are often collectively referred to as Head and Neck Squamous Cell Carcinomas (HNSCCs).

In the UK, around 10,000 new cases of HNSCCs are diagnosed each year, whilst in the US they account for 3-4% of all malignancies diagnosed. They are at least twice as common in men, with a rising incidence.

Of note, Oral cancer incidence is increasing, thought to be linked to immigration and betel quid chewing, oropharyngeal cancer incidence is increasing, thought to be linked to Human Papilloma Virus (HPV) affecting the younger population, whilst laryngeal cancer is decreasing, likely due to reduced smoking rates worldwide.


Risk Factors

Most HNSCCs are linked to modifiable behaviors. Indeed, alcohol and tobacco use account for around 75% of HNSCCs.

Other risk factors* include HPV (mainly type 16, most significantly linked to oropharyngeal cancer), betel quid (linked to oral cancer), occupational wood dust exposure (linked to sinonasal cancer), and EBV infection (linked to nasopharyngeal cancer).

*One study has also noted that high salivary counts of the common bacterial microbiota C. Gingivalis, P. Melaninogenica and S. Mitis could be used as diagnostic indicators for oral cancer, with sensitivity and specificity rates at 80% and 82% respectively.

Premalignant Conditions

Many HNSCCs, typically the oral cancers, may begin as a visible premalignant condition, such as leukoplakia (white patches), erythroplakia (red patches), erythroleukoplakia (mixed red and white patches), oral lichen planus, or actinic cheilitis.

These premalignant conditions are also heavily associated with smoking and alcohol consumption, and have a lifetime risk of transformation ranging from 0-20%. Consequently, most suspected premalignant conditions require further histological assessment in the form of a biopsy.


Clinical Features

Each subtype of HNSCCs can present differently, however it is important to remember non-specific cancer symptoms, such as weight loss and cervical lymphadenopathy, can also be a feature.

Oral Cavity Cancer

Most commonly oral cavity cancers will present as a mass, initially painless, being felt on the inner lip, tongue, floor of the mouth, or hard palate. Less commonly, these cancers will present in more non-specific means*, such as oral cavity bleeding, localised pain within the oral cavity, or jaw swelling.

*Premalignant conditions (erythroleukoplakia) may be noticed initially, prompting further investigations which reveal the malignant transformation

Pharyngeal Cancer

Many cases of pharyngeal cancer can present* initially as odynophagia, dysphagia, stertor, or referred otalgia. Nasopharyngeal carcinoma patients can present initially with a neck lump.

*Trotters Syndrome is a triad of clinical features suggestive of nasopharyngeal malignancy, comprised of (1) unilateral conductive deafness (secondary to middle ear effusion), (2) trigeminal neuralgia (secondary to perineural invasion), and (3) defective mobility of the soft palate +- trismus

Majority of these tumors, specifically of the hypopharynx, frequently will have an advanced stage at the time of diagnosis as they will often metastasise early due to the extensive lymphatic network.

Laryngeal Cancer

The clinical features of a laryngeal malignancy can include hoarse voice, stridor (if advanced), dysphagia, persistent cough, or referred otalgia. Laryngeal cancers are divided anatomically (mainly for the purpose of tumour staging) into glottis, supraglottis, and subglottis, with most malignancies originating in the glottis region.

Patients with glottic tumours have better prognosis as they present earlier with hoarse voice and there is no lymphatic drainage from the glottis, hence limits any metastatic spread locally.

Fig. 2 – HNSCCs in various locations (A) Oral cavity cancer (B) Hypopharyngeal cancer


Investigations

The mainstay of investigation for suspected HNSCC requires biopsy of the lesion, the method by which this is obtained depends on the location.

Most referrals for suspected HNSCCs undergo flexible nasal endoscopy (FNE), allowing for direct visualisation of the lesion. If a lesion is seen, then an examination under anesthesia (EUA) and biopsy will be warranted (in most cases, biopsy will need to be performed under general anaesthetic with the exception of oral cavity lesions)

For those patients presenting solely with lymphadenopathy, they will undergo ultrasound-guided fine needle aspiration (FNA) to assess for evidence of malignant cells.

Staging

Any suspected lesion will typically have a CT scan of the neck and chest used to estimate tumour extension, evidence of local invasion and any cervical lymphadenopathy. The chest is included for staging to assess for any lung metastasis. PET CT scan is occasionally used for tumours of unknown origin.

An MRI scan is superior in assessing oral cavity and oropharyngeal lesions, hence in these patients, they will undergo MRI neck and CT chest scans seperatelyto stage the disease.

Referrals

Current NICE guidance suggests that referral to a specialist centre is warranted when patients present with

  • Laryngeal Cancer
    • Persistent unexplained hoarseness (urgent)
    • Unexplained lump in the neck (urgent)
  • Oral Cancer
    • Lump on the lip or in the oral cavity (urgent)
    • Erythroplakia or erythroleukoplakia (urgent)
    • Unexplained ulceration in the oral cavity for >3 weeks (consider)
    • Persistent and unexplained lump in the neck (consider)

Management

Management of HNSCCs varies greatly depending on the location, size, stage, and grade of the cancer, as well as patient preference and comorbidities.

Surgical resection or primary radiotherapy +/- chemotherapy or surgical resection with post operative radiotherapy +/- chemotherapy are the mainstays of treatment for most HNSCCs.

Surgical management of HNSCC is complex and dependent on a variety of factors. The management plan is discussed in a dedicated head and neck MDT meeting. However, in general:

Oral cavity

Small tumours can undergo wide local excision +/- neck dissection. Recent evidence shows improved survival for patients with oral cavity cancers undergoing elective neck dissection regardless of tumour size

Larger tumours should surgical resection +/- flap reconstruction + neck dissection +/- post operative radiotherapy +/- chemotherapy

Oropharynx

Small tumours of the tonsil can undergo surgical resection using Laser or Transoral Robotic Surgery +/- neck dissection or primary radiotherapy or both (if margin involved). Larger tumours of the tonsil will undergo solely primary radiotherapy +/- chemotherapy

Small tumours at the tongue base will undergo surgical resection using Transoral Robotic Surgery with neck dissection or primary radiotherapy or both (if margin involved). Larger tumours at the tongue base will undergo primary radiotherapy +/- chemotherapy

Larynx

Supraglottis

Small tumours will undergo surgical resection using transoral laser microsurgery with bilateral neck dissection or Primary radiotherapy +/- chemotherapy

Larger tumours will undergo laryngectomy with post-operative radiotherapy +/- chemotherapy or Primary radiotherapy +/- chemotherapy

Glottis

Small tumours will have surgical resection using transoral laser microsurgery with bilateral neck dissection or Primary radiotherapy

Larger tumours undergo laryngectomy with neck dissection and post-operative radiotherapy +/- chemotherapy or primary radiotherapy +/- chemotherapy

Subglottis

Tumours originating from subglottis are very rare but treatment principles are similar to the glottis

Hypopharynx

Small tumours of the hypopharynx can undergo surgical resection using transoral laser microsurgery with neck dissection or primary radiotherapy +/- chemotherapy

Larger tumours should undergo laryngopharyngectomy +/- gastric pull up/jejunal free flap + neck dissection or primary radiotherapy +/- chemotherapy


Prognosis

Prognosis is varied, mainly dependent on the subtype and TNM staging, as shown in the table below*

Site

Stage

All Stages

I II

III

IV

Oral cavity 75.6% 70.3% 62.7% 30.5% 50.2%
Oropharynx 80.3% 64.8% 51.5% 31.4% 40.6%
Hypopharynx 32.9% 48.5% 20.0% 28.1%
Supraglottis 89.9% 73.0% 73.2% 41.8% 62.4%
Glottis 94.0% 86.7% 72.3% 52.4% 85.9%
Subglottis 44.4%

Table 1 – Recurrence Free Survival Rates for Head and Neck Cancers, data adapted from Iro H et al.

*Newer classifications have recently included separate sections for HNSCC secondary to HPV, however these are not universally used at present

A proportion of those treated for head and neck cancers will develop secondary primary malignancies, with rates at 20 years ranging from 9-23%, hence can have an impact on long-term survival after successful treatment of early-stage HNSCC.

Other complications following treatment for head and neck cancers include:

  • Dysphagia (secondary to pharyngeal/oesophageal stricture)
  • Pharyngocutaneous fistula (following laryngectomy)
  • Injury to the accessory, vagus, hypoglossal, abd marginal mandibular nerves (following neck dissection)
  • Chyle leak (following neck dissection)
  • Mucositis (early complication of radiotherapy)
  • Xerostomia (complication of radiotherapy)
  • Chronic pain, persistent hoarse voice, or hearing loss (following chemoradiotherapy)
  • Recurrence

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