Summary

Common head and neck cancers include those of the nasopharynx, larynx, thyroid, tongue, oral cavity, hypopharynx, salivary glands, oropharynx, nasal cavity and sinuses. While the prognosis for small cancers is good, their early detection can be difficult as they may present with vague symptoms that are common to a wide variety of infective, inflammatory and other pathologies. A family physician must be aware of the symptoms and signs of the common head and neck cancers. A careful assessment of symptoms is important and essential to direct a thorough examination of the head and neck. This is not always straightforward, and cancers that occur in the cavities of the head and neck may go undetected by those unfamiliar with the necessary examination techniques. The family physician should be aware of the factors that add to and detract from the patient's quality of life and remain actively involved in all aspects of a patient's management and follow-up.

摘要

常見的頭頸部癌症包括鼻咽、喉、甲狀腺、舌、口腔、下咽部、唾液腺、口咽、鼻腔和各竇的癌症。較小的癌預後雖好，但卻難以被早期發現，因為其症狀並不明顯並常可見於各種感染性、炎性及其它疾病。家庭醫生必須瞭解頭頸部常見癌症的症狀和體症。進行認真的症狀評估，對指導頭頸部全面檢查十分重要和必要。但有時檢查並不簡單，若不熟悉必要檢查技術，可能難以發現頭頸部各腔內的癌症。家庭醫生應瞭解可能改善和降低病人生命質素的各種因素，並積極參與病人各方面治療和隨訪。

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The common head and neck cancers

Nasopharyngeal carcinoma (NPC) is the commonest head and neck cancer and the 6^th commonest overall cancer in men, while thyroid cancer is the commonest head and neck cancer and the 10^th commonest overall cancer in women (Table 1).¹ In the 20 - 44 year old age group however, NPC is the commonest cancer in men, thyroid cancer is the 2^nd commonest cancer in women and NPC the 4^th commonest cancer in women (Table 2).¹ The incidence and sites of the commonest primary head and neck cancers in men and women are shown in Figure 1.¹

Basic anatomy

There are seven major air-containing cavities in the head and neck. The pharynx is the common posterior passage which has 3 parts. The nasopharynx lies posterior to the nasal cavity, the oropharynx lies posterior to the oral cavity and the laryngopharynx, more commonly called the hypopharynx, lies posterior to the larynx. The paranasal sinuses, or sinuses, open into the nasal cavity. The other air-containing cavities in the head and neck are the eustachian tube/middle ear/mastoid complex, the cervical oesophagus and the cervical trachea.

All head and neck cavities are lined by epithelium which is derived embryologically from either ectoderm or endoderm. The epithelium is covered by a layer of mucus secreted by goblet cells and subepithelial mucous glands, and so can also be referred to as the mucosa lining.

Aetiology

Healthy epithelium can undergo malignant change to become carcinoma. Carcinogenic factors causing this include tobacco, alcohol, genetic factors (for example an abnormal p53 gene²), radiation (either background, diagnostic or therapeutic) and viral infections (for example Epstein-Barr virus (EBV)³ or Human Papilloma virus type 16 (16HPV-16)). Oral cavity

The primary tumour (T-stage)

Three different stages in the progression of normal epithelium to carcinoma can be recognized under the light microscope. Healthy epithelium progresses to hyperplastic epithelium, which then progresses to dysplastic epithelium, which then progresses to carcinoma-in-situ and finally becomes invasive carcinoma. This is the primary tumour or the T-stage in the TNM classification. Hyperplasia is an increase in the size of a tissue due to an increase in the number of cells. The increased rate in cell-division may lead to abnormal DNA and genetic errors accumulating. Hypertrophy is an increase in the size of tissue due to an increase in the size of cells and cell-division does not occur. Metaplasia, a change of one type of epithelium to another type of epithelium, is not generally a pre-malignant condition in the head and neck.

Carcinoma can either grow above the mucosal surface as an exophytic, fungating, polypoid growth, or below the surface as an infiltrating, ulcerating or endophytic growth. There is often necrosis in the centre of the primary tumour as the tumour outgrows its own blood supply, resulting in the central portion becoming ischaemic and eventually necrotic. As the primary tumour grows, it invades local structures and lymphatic vessels.

Regional lymph nodes of the head and neck (N-stage)

Once the tumour has invaded lymphatic vessels, malignant cells break off and travel to regional lymph nodes, where they are trapped and grow as regional lymph node metastases. The N-stage in the TNM classification refers to regional lymph nodes involvement. Regional lymph node metastases may also develop central necrosis.

The regional lymph nodes of the head and neck are named according to their position in the neck, relative to the triangles of the neck and the internal jugular vein. The regional lymph nodes of the head and neck are the submandibular lymph nodes, found in the submandibular triangle (level I lymph nodes); the upper, middle and lower jugular nodes which lie deep to the upper, middle and lower thirds of the sternomastoid muscle respectively (levels II, III and IV lymph nodes), and posterior triangle lymph nodes found within the posterior triangle of the neck (level V lymph nodes) as shown in Figure 2.⁴

Lymph from the mucosa of all the head and neck cavities drains to regional head and neck lymph nodes. Lymph from the mucosa of the nasal cavity, sinuses and oral cavity drains to submandibular lymph nodes (level I) while lymph from the whole pharynx (naso-, oro- and hypo-pharynx) and the larynx drains to upper jugular lymph nodes (level II) as shown in Figure 3.

Lymph from submandibular nodes drains to upper jugular lymph nodes. Lymph from upper jugular nodes drains to mid-jugular and then to lower jugular nodes and then into the upper mediastinum. Thus lymph from the mucosa of the head and neck drains along predictable pathways in a step-wise fashion. Using this information, the likely site of a primary carcinoma can be determined in someone who presents with an enlarged neck node due to metastatic carcinoma.

Symptoms of common head and neck cancers

Symptoms, what the patient complains of, will direct the physician's examination for signs. Symptoms of common head and neck cancers may be vague and overlap with symptoms of many common non-malignant infective and inflammatory head and neck conditions and so a physician needs to maintain a high index of suspicion. Unfortunately, no symptom or symptom complex strongly correlates with early head and neck cancer⁵.

Symptoms of common head and neck cancers are shown in Table 3.

Signs of common head and neck cancers

Malignant epithelium or carcinoma begins with a change of appearance of normal mucosa on inspection, becoming more red or being whiter than surrounding mucosa, or a change in consistency on palpation, being thickened or nodular compared to normal mucosa. As the size of malignancy increases, a discernable ulcer often becomes apparent, and as it grows, the central area becomes necrotic and has the appearance of slough. The ulcer may be flush with the surrounding mucosa, in which case there will be an area of underlying induration on palpation of the ulcer, or the ulcer may occur on the surface of a mucosal mass or lump.

Another common presenting sign of a head and neck cancer is a neck lump, which is discussed under that subheading below.

Basic examination of the head and neck

Physicians learn from their patients, especially what is 'normal'. Thus experience, which comes from examining a lot of normal patients, allows physicians to quickly differentiate normal from abnormal, be it a symptom or a sign.

The detection of squamous cell carcinoma of the head and neck mucosa is by inspection of all the head and neck mucosa. Inspection of all the head and neck mucosa requires expertise and experience and proficiency in the use of endoscopes, an instrument with a lens system that allows magnification and illumination of a cavity. For this reason, patients in which a physician suspects a malignancy should be referred to an ENT Surgeon / Otorhinolaryngologist for further assessment so as to avoid a delay in the management of head and neck cancers. Any abnormal looking mucosa must be biopsied to obtain a histological diagnosis of the mucosal abnormality.

The patient with a neck lump

In the same way that the breast of a patient who presents with an enlarged axillary lymph node should be examined to exclude a primary tumour in the breast, so too should all of the mucosa of the head and neck cavities be examined to exclude a primary tumour in a patient who presents with a lateral neck lump.

The rationale is that a carcinoma of the epithelium or mucosa of one of the cavities of the head and neck will initially drain or metastasize to the regional lymph nodes which drain that particular cavity.

While a neck lump is always abnormal, there are normal anatomical structures that may feel like a neck lump on palpation (Figure 4). The position of the mass in the neck may also indicate its origin (Figure 5).

As a general rule in adults, 80% of upper lateral neck lumps will be malignant, 80% of these will be metastatic, in 80% of these the pathology will be a carcinoma, 80% of which will come from a primary in the head and neck. In 80% of these cases, the primary is usually found when the head and neck is examined as described above.

The bottom line therefore, is that every effort must be made to exclude a primary head and neck cancer in a patient who presents with an upper lateral neck mass. The history must include questions about symptoms of malignancy in the cavities of the head and neck, and each cavity examined to detect a primary carcinoma.

If a suspicious mucosal lesion is found, it should be biopsied to confirm the diagnosis. If no suspicious mucosal lesion is found, a fine needle aspiration for cytology (FNAC) of the mass should be done to confirm the nature of the mass. An FNAC requires a 10-20ml syringe, a 22 gauge (G) needle, two glass slides and fixative spray (one smear is air dried and the other fixed with fixative spray as soon as the smear is completed) or a specimen bottle with 25% alcohol. An FNAC is easily performed if the mass can be felt. If the mass proves to be a metastatic carcinoma, imaging is used to identify the primary, with either computed tomography (CT) scanning or magnetic resonance imaging (MRI). Advances with colour Doppler sonography, spiral CT scanning, MRI, and positron emission tomography (PET) imaging have revolutionized the way in which tissues can be examined⁶. Ultimately the patient may need to undergo an examination under anaesthesia (EUA) or panendoscopy to re-examine all the cavities of the head and neck under ideal conditions, including the hypopharynx and cervical oesophagus which are collapsed and are difficult to examine fully in an awake patient. If no obvious lesion is found and if imaging has been unhelpful, then biopsies of the five common sites of head and neck carcinoma primaries are taken while the patient is under general anaesthesia to exclude a microscopic primary. The sites biopsied are the nasopharynx, tonsil, base of tongue, supraglottis and pyriform fossa.

In an adult with a lateral neck mass, an incisional or excisional biopsy should not be performed unless FNAC, imaging and an examination under anaesthesia have failed to find the primary tumour.

Nasopharyngeal carcinoma

The incidence of NPC in Hong Kong is 20:100000 men (700 cases) and 6.7:100000 women (234 cases) per year (934 cases per year) (Year 2003 figures).¹

Diagnosing NPC is not straight forward and requires experience and suitable equipment. A high index of suspicion is needed as symptoms of NPC, especially in the early stages, are vague. This is compounded by the fact that up to 5% of cases of NPC may have a normal looking nasopharynx on examination, if the physician has the ability to confidently perform it. This is the reason that EBV serology has become part of the diagnostic work-up in most centres. The objective of serology is to predict or exclude a diagnosis of NPC.

Serum EBV IgA-VCA is sensitive but not very specific, while EBV IgA-EA is specific but not very sensitive. EBV IgA-VCA is useful if negative but not if positive (a titre of 1:40). EBV IgA-VCA is one of the more sensitive assays for NPC and if negative has a negative predictive value of 96.1% that a patient does not have NPC⁷. On the other hand, it is not very specific for NPC if positive, with a positive predictive value for NPC of only 44%⁷. EBV IgA-EA is useful if positive but not if negative (a titre of < 1:10). EBV IgA-EA is one of the more specific assays for NPC and if positive has a positive predictive value of 88.9% that a patient does have NPC⁷. While IgA-EA is used to eliminate false-positive IgA-VCA results, it has a sensitivity for detecting NPC of only 72.7%⁷.

As no single test can reliably predict and exclude NPC, the two tests are used in combination to improve their overall accuracy, with VCA having a high negative predictive value and EA a high positive predictive value.

VCA is used as a screening test to exclude NPC, and if positive, EA is used to determine if the VCA is truly or falsely positive. If both tests are positive, the patient should be worked up for NPC, and if both are negative, the patient most likely does not have NPC. The chances that a patient with an equivocal result has NPC, i.e. a positive VCA but negative EA, is 14.7%. Similarly, in 15% of patients with NPC, the EBV IgA-VCA titre may not be raised.⁸

The detection of circulating cell-free EBV DNA has been reported to range from 75% to 90% of patients with NPC⁹ and for stage I and II NPC¹⁰. As the sensitivity of cell-free EBV DNA for NPC is higher than that of IgA-EA, the use of cell-free EBV DNA to eliminate false-positive IgA-VCA results may offer an improvement in the overall detection of NPC. It must be remembered however that the concentrations of EBV DNA and IgA- VCA titers do vary according to cancer stage.¹⁰

MRI is also highly diagnostic of NPC with a sensitivity of 100%, a specificity of 95% and an accuracy of 95%.¹¹

Thyroid tumours

Thyroid swellings are commonly encountered in clinical practice.¹² Thyroid cancer presents as a lower neck mass that moves on swallowing, and in the later stages may present with hoarseness, dysphagia or cervical lympadenopathy. The initial investigation of choice is ultrasonography (USG) with FNAC if indicated.

About 5% of adults have palpable thyroid nodules. Although fewer than 10% of these nodules will be malignant, all thyroid nodules should undergo USG and FNAC.¹³ Ultrasonography will determine whether the nodule is solitary or not, whether the nodule shows any signs of malignancy or not and whether any abnormal regional lymph nodes are present or not. The cytology of the nodule will help the clinician to determine the next investigation or procedure to be performed.

Salivary masses

About 80% of salivary gland tumours occur in the parotid gland, of which 20% will be malignant; 15% of salivary gland tumours occur in the submandibular gland, of which 50% will be malignant; and 5% of salivary gland tumours occur in the sublingual or minor salivary glands, of which 60% - 80% will be malignant.¹⁴ A lump in a salivary gland needs further investigation by a specialist, including imaging and FNAC, prior to excision.

The patient's quality of life

Advanced cancers usually have a bigger effect on a patient's quality of life (QOL) than early cancers.¹⁵ Understanding which aspects of a patient's ability to enjoy normal life activities are affected by a cancer will enable the family physician to provide support and possible interventions. Unfortunately, some treatments impair a patient's QOL without adding much benefit. The effects of the cancer, the loss of normal head and neck function and the side-effects of treatment have a large impact on the patient's QOL.¹⁵

Factors that negatively affect the sense of physical well-being of a patient with or treated for head and neck cancer include pain, xerostomia, breathing problems, nausea, a feeling of being unwell, listlessness and the need for bed rest.¹⁶ Factors that negatively affect the sense of emotional well-being of a patient include sadness, nervousness, worrying about dying, worrying about deteriorating and losing hope of improving.¹⁶ Factors that positively affect the sense of family and social well-being of a patient include closeness to and emotional support from family and friends, family acceptance of the illness, a normal voice and the ability to communicate vocally.¹⁶ Factors that positively affect the sense of functional well-being of a patient include the ability to work, deriving fulfillment from work, the ability to enjoy life, ability to enjoy leisure pursuits, acceptance of their illness and sleep quality.¹⁶ The ability to chew and swallow a variety of foods normally and easily also adds to a sense of well-being.

The role of the family physician

The family physician has a prophylactic role (education, screening, detection) and therapeutic role (treatment, follow-up, palliation) to play in patients with head and neck cancer.

The prophylactic role includes educating patients in terms of exercise, a healthy diet, the risks of tobacco and alcohol and holding public information conferences. Screening for head and neck cancer is achieved by briefly asking the patient about pain, blood, lumps, breathing, chewing and swallowing problems and other symptoms of head and neck cancer. All possible mucosa in the head and neck should be inspected and the neck palpated in every potentially at-risk patient, especially in those who present with suspicious symptoms.

The therapeutic role includes treatment, follow-up and palliation. Good communication between the family physician and the patient is essential to allow the family physician to offer psychosocial support, care for the whole person at all stages, deal with realistic expectations of outcome, discuss appropriateness of "alternative" or "complementary" therapies and offer counselling to the patient and family. Collaboration between the family physician and the specialist is essential for optimal rehabilitation and follow-up, to restore quality of life, to repair the patient's self-confidence and to rebuild the patient's psychosocial sense of well-being. If the patient's illness is no longer curable, palliation includes pain control with pharmacological agents, psychological counselling, management of depression, emotional support and compassion for the patient.

Factors contributing to a delayed diagnosis of head and neck cancer

Head and neck cancer screening programmes have not yet been shown to improve survival and so early detection of cancer in response to patient symptoms remains the mainstay of secondary prevention.¹⁷ A significant increased risk of a tumour-related death in patients when the diagnosis is missed at initial presentation has been shown. However, an initial misdiagnosis is not serious provided the patient is followed up within 3-4 weeks. In other words, family physicians need to keep the possibility of cancer in mind, and if no immediate referral is made, then at least follow-up the patients whose symptoms and signs are difficult to define conclusively. This is particularly important in patients who present with hoarseness, ulcers or pain.¹⁷

It has also been shown that patient's delay in initially seeing a family physician is the most significant factor in delaying the diagnosis of head and neck cancer. Fortunately this can be improved by education.¹⁸

A diagnosis of head and neck cancer is often not made at the initial consultation with the family physician. A delay in diagnosis due to the patient not returning to the family physician is partly due to patient-related factors, such as their personality and interpretation of their symptoms. For example, patients not familiar with head and neck cancer or not suspicious that their symptoms may indicate head and neck cancer are at an increased risk of delaying their return to their family physician. To counter this, patients should be educated about the possible meaning of their symptoms and should be strongly advised to return within three to four weeks if symptoms do not disappear. Further, family physician should actively follow-up their patients who they suspect have head and neck cancer.¹⁸

When the family physician suspects cancer, the family physician must indicate this in their referral letter to the specialist to minimize delays that occur because of inappropriate prioritizing in giving appointment dates.¹⁸

Conclusion

The family physician needs to be a versatile player in the health care of patients and the community. The family physician needs to educate them about the causes, symptoms and signs of head and neck cancer. The family physician needs to maintain a high index of suspicion when a patient presents with vague head and neck symptoms, and needs to be skilled to carry out a thorough head and neck examination, especially to detect early cases of head and neck cancer. The family physician must investigate symptoms and signs appropriately, and refer the patient to a cancer centre with clear documentation when indicated. The family physician should remain actively involved in all aspects of the patient's subsequent management and follow-up.

Key messages

1. Cancer is the main cause of death in Hong Kong, 10% of which occurs in the head and neck.
2. Community and patient education about the causes of cancer, such as alcohol and tobacco use, and the prevention of cancer, such as a healthy diet and lifestyle, will reduce the incidence of cancer.
3. . Community and patient education about the symptoms and signs of cancer will reduce the delay in patients initially consulting their family physician with suspicious symptoms or in returning for follow-up for symptoms that have not resolved in a couple of weeks.
4. Head and neck cancer usually arises from the epithelium (mucosa) of the head and neck cavities, but the salivary glands and thyroid gland can also become malignant.
5. Head and neck cancer occurs in the nasopharynx (45%), the thyroid gland (21%), the oral cavity and oropharynx (13%), the hypopharynx and larynx (13%), the salivary glands (3%) and the nasal cavity and sinuses (2.5%).
6. Symptoms of head and neck cancer include pain, a mucosal abnormality such as thickening or ulceration or a lump, difficulty in chewing or swallowing, difficulty in breathing, hoarseness, nasal obstruction and blood stained saliva or nasal secretions.
7. Head and neck cancers often present as a metastatic neck lump, in which case every effort must be made to find the primary tumour.
8. When a head and neck cancer is suspected, all the mucosa of the head and neck cavities must be carefully inspected and any abnormal looking mucosa biopsied.
9. A neck lump should be investigated with ultrasound imaging and fine needle aspiration cytology if the cause is not obvious.
10. Ask relevant questions, inspect all available head and neck mucosa and palpate the neck for lumps in patients with a family history of cancer or a history of tobacco or alcohol use during their annual check-up.

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References