Head & Neck Tumors
Head and neck oncology is usually taught as a tour of anatomical subsites, which makes it feel like a list to be memorised.
Three ideas organise almost all of it.
The first is that head and neck cancer is a field disease, not a tumour. The carcinogen bathes an entire mucosal surface, so the visible lesion is the worst part of a diseased field, and second primaries are common.
The second is that two different carcinogens produce two different diseases in the same anatomy. Tobacco and areca nut produce one disease. Human papillomavirus produces another. They differ in patient, site, behaviour, staging and prognosis, and treating them as one condition produces wrong answers.
The third is that a neck node is a map. Its level tells you which mucosal surface drained into it, and that is usually enough to find the primary.
India makes the first two urgent rather than academic. Head and neck cancer accounts for roughly 30 per cent of all cancers in India, and the country carries the largest oral cavity cancer burden in the world, with figures around 1,20,000 new oral cancers and over 72,000 deaths in a single reported year.
1. The Indian Disease: Tobacco and Areca Nut
India is the global centre of smokeless tobacco use, and the pattern of disease follows the habit rather than the cigarette.
Chewed products held in the buccal sulcus produce cancer where they sit. This is why the buccal mucosa, gingivobuccal sulcus and tongue dominate Indian series, while Western series are weighted toward larynx and oropharynx.
Field cancerisation
Slaughter's concept explains the clinical behaviour. The whole exposed mucosa accumulates genetic damage, so the visible tumour sits in a field of abnormal but not yet malignant epithelium.
Two consequences follow. Resection with clear margins does not remove the risk, and second primary tumours arise at a steady rate for years afterwards. Surveillance of the whole upper aerodigestive tract, not just the operated site, is therefore part of treatment.
The premalignant lesions
| Lesion | Appearance | Malignant potential |
|---|---|---|
| Leukoplakia | White patch that cannot be rubbed off | Low to moderate |
| Erythroplakia | Red velvety patch | High, much greater than leukoplakia |
| Oral submucous fibrosis | Blanching, fibrous bands, progressive trismus | Substantial, and irreversible |
Leukoplakia is a clinical diagnosis of exclusion, meaning a white patch not attributable to any other cause. Erythroplakia looks less dramatic and behaves far worse, which is exactly why it is examined.
Oral submucous fibrosis is the areca nut disease and is largely an Indian and South Asian condition. Arecoline drives collagen deposition in the lamina propria, producing pale, marble-like mucosa with palpable vertical bands and progressively limited mouth opening.
The fibrosis does not reverse when the habit stops, though progression slows. Trismus also makes later examination and intubation difficult, which matters for anaesthesia as much as for oncology.
2. The HPV Disease
Human papillomavirus, chiefly type 16, causes a distinct oropharyngeal cancer centred on the tonsil and base of tongue.
The patient is typically younger, often a non-smoker, and the tumour frequently presents as a cystic neck node at level II with a small or clinically invisible primary.
p16 immunohistochemistry is the accepted surrogate marker, read as positive when there is diffuse staining in at least 75 per cent of tumour cells with at least moderate intensity.
The prognosis is so much better that the AJCC 8th edition gives HPV-associated oropharyngeal cancer its own staging system, separate from HPV-negative oropharyngeal and hypopharyngeal disease, and separate again from nasopharynx. It also introduced distinct clinical and pathological staging for the first time in this region.
A caution worth carrying, because much revision material has not caught up. The excellent prognosis prompted trials of de-intensified treatment. NRG-HN005 was halted when the standard chemoradiation control arm reached a two-year progression-free survival of 98 per cent, better than the de-intensified arms.
So the current position is that standard chemoradiation remains the reference treatment for selected HPV-positive patients, and de-intensification is a research question rather than established practice.
3. The Neck Node as a Map
Cervical nodes are described in levels, and each level drains a predictable territory.
| Level | Region | Usual primary |
|---|---|---|
| I | Submental, submandibular | Oral cavity, lip, anterior tongue |
| II | Upper jugular | Oropharynx, tonsil, base of tongue, larynx |
| III | Middle jugular | Larynx, hypopharynx, oropharynx |
| IV | Lower jugular | Hypopharynx, subglottis, and infraclavicular primaries |
| V | Posterior triangle | Nasopharynx, thyroid, scalp |
| VI | Central compartment | Thyroid, subglottis, cervical oesophagus |
Two entries change the whole differential.
A level V posterior triangle node points to the nasopharynx. A level IV or supraclavicular node, particularly on the left, points below the clavicle, to lung, stomach, pancreas or breast, and the Virchow node is that finding.
A firm, painless, enlarging neck node in an adult over 40 is a metastasis until proved otherwise.
The rule about biopsy
Do a fine needle aspiration. Do not do an excisional biopsy of a neck node in suspected malignancy.
Excision violates tissue planes, seeds the operative field, disrupts the lymphatic anatomy that later surgery depends on, and is associated with worse local control. It converts a straightforward neck dissection into a difficult one.
If cytology is inconclusive, a core biopsy is the escalation, ideally by the team that will treat the patient.
Finding an unknown primary
When cytology shows squamous carcinoma but examination finds no primary, two stains on the nodal material do most of the localising.
p16 positivity points to the oropharynx. EBER in situ hybridisation for Epstein-Barr virus points to the nasopharynx.
Cross-sectional imaging and PET-CT follow, then examination under anaesthesia with panendoscopy and directed biopsies, including of the tonsil and tongue base.
4. Larynx: Why Site Predicts Behaviour
The larynx demonstrates the value of anatomy better than any other subsite, because lymphatic supply differs sharply above and below the true cords.
The true vocal cords have almost no lymphatic drainage. The supraglottis has a rich bilateral supply.
| Subsite | Presentation | Nodal spread | Prognosis |
|---|---|---|---|
| Glottic | Early, with hoarseness | Late, sparse lymphatics | Better |
| Supraglottic | Late, vague throat discomfort or referred otalgia | Early and often bilateral | Worse |
Persistent hoarseness for more than three weeks in an adult requires laryngoscopy. Nothing about the history reliably excludes carcinoma, and glottic cancer caught while it is still confined to the cord is highly curable.
Referred otalgia with a normal ear examination is a genuine warning sign, mediated through the vagus and glossopharyngeal nerves, and it is a common way for supraglottic and hypopharyngeal tumours to announce themselves.
5. Nasopharyngeal Carcinoma
Nasopharyngeal carcinoma is a separate disease with a separate cause, a separate epidemiology and a separate treatment.
It is driven by Epstein-Barr virus, and the classical histology is undifferentiated non-keratinising carcinoma. Beyond southern China, there is a notably raised incidence in parts of northeast India, which is worth knowing for Indian examinations.
The presentation follows the anatomy of the fossa of Rosenmuller.
A neck node is the commonest presenting complaint. Blockage of the Eustachian tube orifice produces unilateral serous otitis media, and epistaxis or nasal obstruction follows local growth. Skull base extension produces cranial nerve palsies.
Unilateral serous otitis media in an adult is nasopharyngeal carcinoma until the nasopharynx has been examined. A child with glue ear is ordinary; an adult with a one-sided middle ear effusion is not.
Because the tumour is radiosensitive and surgically inaccessible, treatment is radiotherapy, with chemoradiation for advanced disease. Surgery has no primary role, which reverses the usual instinct.
The other nasopharyngeal tumour
Juvenile nasopharyngeal angiofibroma is benign, occurs almost exclusively in adolescent boys, and behaves badly because it is intensely vascular and locally aggressive.
It arises at the sphenopalatine foramen and presents with recurrent profuse epistaxis and progressive nasal obstruction in a teenage boy. Anterior bowing of the posterior maxillary wall on imaging is the Holman-Miller sign.
Biopsy is contraindicated. The lesion is a mass of vessels without contractile muscle in their walls, so biopsy can produce torrential haemorrhage. The diagnosis is made on contrast imaging, which shows the characteristic blush and feeding vessels.
Treatment is surgical excision, usually after preoperative embolisation to reduce blood loss. The examination point is simply that a teenage boy with recurrent heavy epistaxis and a nasopharyngeal mass is never biopsied in clinic.
6. Salivary Gland Tumours
One rule does most of the work: the smaller the gland, the greater the chance that a tumour in it is malignant.
Most parotid tumours are benign. Submandibular tumours are malignant more often, and minor salivary gland tumours of the palate more often still.
| Tumour | Features |
|---|---|
| Pleomorphic adenoma | Commonest salivary tumour, benign, recurs if enucleated |
| Warthin tumour | Smokers, older men, may be bilateral, technetium-avid |
| Mucoepidermoid carcinoma | Commonest salivary malignancy, graded low to high |
| Adenoid cystic carcinoma | Perineural spread, late lung metastases, long survival with disease |
Three examinable points follow.
Facial nerve palsy with a parotid mass means malignancy until proved otherwise. Benign tumours displace the nerve; they do not paralyse it.
Pleomorphic adenoma must never be enucleated. It has microscopic pseudopodia beyond an incomplete capsule, so enucleation leaves tumour behind and produces multifocal recurrence that is far harder to treat. Superficial parotidectomy is the operation.
Adenoid cystic carcinoma spreads along nerves, which explains pain, unexpected cranial nerve deficits and margins that are positive far from the visible tumour. It metastasises late to lung, and patients often live many years with known metastatic disease.
Frey syndrome is the late complication of parotidectomy: sweating and flushing of the cheek while eating, caused by regenerating parasympathetic secretomotor fibres reinnervating the sweat glands of the overlying skin.
7. Principles of Treatment
Early disease is treated with a single modality, either surgery or radiotherapy, chosen by function and morbidity rather than by efficacy.
Advanced disease is treated with combined modalities, typically surgery with adjuvant radiotherapy, or concurrent chemoradiation.
Adjuvant radiotherapy is indicated for adverse pathological features, and positive margins or extranodal extension are the two findings that add concurrent chemotherapy to postoperative radiotherapy.
The neck is addressed when the risk of occult metastasis is significant, generally taken as around 20 per cent, which is why an elective neck dissection is offered in many clinically node-negative oral cancers.
Reconstruction is part of oncological planning rather than an afterthought, because speech and swallowing determine whether a cured patient has an acceptable life.
Two staging changes worth knowing
The AJCC 8th edition made two changes that matter clinically rather than administratively, and both reward the surgeon who measures rather than eyeballs.
Depth of invasion now contributes to the T stage in oral cavity cancer. A wide superficial tumour and a small deeply invasive one are no longer equivalent, because depth predicts nodal spread far better than surface diameter does.
Extranodal extension now upstages the N category. A node whose capsule has been breached behaves quite differently from one of the same size that has not, and this is the change that most often moves a patient into needing concurrent chemotherapy with postoperative radiotherapy.
Both changes reflect the same underlying principle: the measurements that predict behaviour are the ones describing how the tumour interacts with the tissue around it, not how large it looks.
8. Worked Examples
Example 1. A 46-year-old man has a firm, painless 3 cm level II neck node for two months. Examination of the oral cavity, oropharynx and larynx is normal. A colleague proposes excision biopsy of the node. Comment.
Excision biopsy is the wrong step and is actively harmful. It violates tissue planes, seeds the field, disrupts the lymphatic anatomy that a subsequent neck dissection depends on, and is associated with worse local control.
The correct sequence is fine needle aspiration cytology first, escalating to core biopsy if inconclusive. If cytology shows squamous carcinoma, request p16 and EBER on the material, since p16 positivity points to the oropharynx and EBV positivity to the nasopharynx. Then image with cross-sectional scanning and PET-CT, and perform examination under anaesthesia with panendoscopy and directed biopsies of the tonsil and tongue base.
Example 2. A 38-year-old man from Madhya Pradesh who chews gutkha has progressive difficulty opening his mouth. The buccal mucosa is pale and marble-like with palpable vertical bands. What is the diagnosis and what should he be told?
Oral submucous fibrosis, driven by arecoline in the areca nut. He should be told two things clearly. First, the condition is premalignant with substantial risk of malignant transformation, so he needs regular examination of the whole oral mucosa rather than reassurance. Second, the fibrosis is not reversible: stopping the habit slows progression and reduces cancer risk but will not restore mouth opening. Trismus also complicates later examination and intubation, which should be recorded in case he needs anaesthesia.
Example 3. A 55-year-old woman has had a blocked left ear with hearing loss for two months. Otoscopy shows a dull, retracted left tympanic membrane with an effusion. The right ear is normal. She is otherwise well. What must be excluded?
Nasopharyngeal carcinoma. Unilateral serous otitis media in an adult is not a primary middle ear disease; it is a sign that something is obstructing the Eustachian tube orifice. Glue ear in a child is ordinary because of adenoidal hypertrophy and a horizontal tube, but a one-sided adult effusion demands examination of the nasopharynx by nasendoscopy, with biopsy of anything abnormal. Inserting a grommet without inspecting the nasopharynx would relieve the symptom and miss the cancer.
Example 4. Two patients present with T2 laryngeal cancers, one glottic and one supraglottic. Both have been symptomatic for a similar period. Why do their outcomes differ so much?
Because lymphatic anatomy differs sharply across the laryngeal ventricle. The true vocal cords have almost no lymphatic drainage, so glottic tumours metastasise to the neck late. They also cause hoarseness while still small, so they are detected early.
The supraglottis has a rich, bilateral lymphatic supply, so supraglottic tumours spread to nodes early and often on both sides. They also produce only vague throat discomfort or referred otalgia, so they present late. The combination of earlier detection and later spread makes the glottic tumour substantially more curable at the same T stage.
Example 5. A 60-year-old man has a slowly growing parotid mass and new weakness of the ipsilateral angle of the mouth. What does the facial weakness signify, and what would be the wrong operation?
Facial nerve palsy with a parotid mass indicates malignancy until proved otherwise, because benign tumours displace the facial nerve rather than paralyse it. Nerve infiltration implies an invasive carcinoma, and adenoid cystic carcinoma in particular spreads along nerves and can produce deficits well beyond the palpable mass.
The wrong operation is enucleation. It is wrong for malignancy for obvious reasons, and it is also the classic error for pleomorphic adenoma, which has microscopic pseudopodia through an incomplete capsule and recurs multifocally if shelled out. Diagnosis proceeds by imaging and fine needle aspiration, and surgery is planned as a formal parotidectomy with appropriate nodal and adjuvant treatment.
Summary
Head and neck cancer is a field disease, so second primaries are expected and whole-tract surveillance is part of treatment.
Tobacco and areca nut give India the world's largest oral cavity burden and roughly 30 per cent of all Indian cancers.
Erythroplakia carries far higher malignant potential than leukoplakia despite looking less alarming.
Oral submucous fibrosis is the areca nut disease, premalignant and irreversible.
HPV-16 causes a distinct oropharyngeal cancer in younger, often non-smoking patients, frequently presenting as a cystic level II node.
p16 is the surrogate marker, positive at diffuse staining in at least 75 per cent of cells with moderate intensity.
AJCC 8 stages HPV-positive oropharyngeal cancer separately because prognosis differs so much.
De-intensification is not current standard practice: NRG-HN005 stopped when standard chemoradiation outperformed it.
Node level maps to primary site: I oral cavity, II and III oropharynx and larynx, V nasopharynx.
A left supraclavicular node points below the clavicle; that is the Virchow node.
Fine needle aspiration, never excisional biopsy, for a suspected malignant neck node.
For an unknown primary, p16 points to oropharynx and EBER to nasopharynx.
Glottic cancer presents early and spreads late; supraglottic presents late and spreads early.
Hoarseness beyond three weeks requires laryngoscopy.
Nasopharyngeal carcinoma is EBV-driven, radiosensitive, and treated with radiotherapy rather than surgery.
Unilateral serous otitis media in an adult means examine the nasopharynx.
The smaller the salivary gland, the more likely a tumour in it is malignant.
Facial palsy with a parotid mass means malignancy until proved otherwise.
Never enucleate a pleomorphic adenoma; adenoid cystic carcinoma spreads perineurally.
Positive margins and extranodal extension are what add chemotherapy to postoperative radiotherapy.
