Nasopharyngeal Carcinoma Comprehensive Study Notes

Introduction & General Overview

Nasopharyngeal carcinoma (NPC) = malignant tumour arising from epithelial lining of nasopharynx.
One of the commonest epithelial cancers in adults, yet considered uncommon globally except in defined endemic pockets.
Historical difficulty: nasopharynx is anatomically hidden → late recognition, missed or delayed diagnoses.

Anatomy of the Nasopharynx

Hollow, mucosa-lined conduit between nasal cavity and oropharynx.
Boundaries
• Anterior: posterior choanae + nasal cavity.
• Roof/Superior: sphenoid bone & clivus.
• Posterior: clivus + first cervical vertebra (C1).
• Inferior: soft palate & oropharynx.
• Lateral: Eustachian (pharyngotympanic) tubes + torus tubarius.
Key recess: Rosenmüller’s fossa (posterior to torus tubarius) → most frequent origin site of NPC.
Histology of mucosa: stratified squamous OR pseudostratified ciliated columnar; interspersed salivary glands + lymphoid tissue.

Physiological Functions

Conducts air warmed/humidified in nasal cavity toward larynx/trachea.
Via Eustachian tube (ET) maintains middle-ear aeration & pressure equilibrium across tympanic membrane → essential for hearing.
Resonating chamber for speech – shapes voice quality.

Epidemiology

Global incidence: generally low; endemic clusters in Southern China, South-East Asia, Alaska.
Reported incidence range $10\text{–}53$ / $100\,000$ per year in high-risk areas.
Africa: $5\text{–}7$ / $100\,000$ annually (Hila et al., 2009).
Ghana: NPC = $1.2\%$ of all cancers; $29\%$ of head-and-neck cancers (Larsen-Reindorf et al., 2014).
Endemic areas may attribute $18\text{–}25\%$ of all cancers to NPC (Breda et al., 2010).
Age distribution: bimodal → peak in $4^{\text{th}}\text{–}5^{\text{th}}$ decade & smaller peak during late teens/childhood.
Sex ratio: male:female $2\text{–}3:1$ .

Aetiology & Risk Factors (Multifactorial)

Genetic Susceptibility

Dramatic ethnic gradient: Southern Chinese (Fujian, Cantonese) ≈ $100\times$ risk versus Caucasians.
Migrant studies: 2nd-generation Southern Chinese in low-incidence countries maintain elevated risk → heritable component.
Reported molecular alterations:
• Chromosome $3p$ & $9p$ allelic loss → inactivation of tumour suppressors $p14,\,p15,\,p16$ .
• Mutations/aberrant regulation: $AKT1,\,p53,\,MDM2,\,LMP1,\,PTEN$ .
• Pathogenesis research: Dawson, Jiang, Zhang et al.

Viral

Epstein–Barr virus (EBV) is tightly linked to endemic (non-keratinising) NPC.
Serology: elevated IgA & IgG anti-viral capsid antigen (VCA) / early antigen (EA).
• IgA-VCA positive in $80\text{–}85\%$ of NPC; titres fall post-treatment ⇒ marker for monitoring.
Ghana study: EBV type 2 isolated in $52\%$ of NPC patients (Ayee et al., 2020).

Dietary / Environmental

Frequent childhood intake of dry salted, ungutted fish (nitrosamine-rich), shrimp paste, pickled vegetables, soy beans ↑ risk.
Protective: fresh fruit & vegetables – vitamin C inhibits nitrosation.

Other Exposures

Cigarette smoke, alcohol, wood dust, incense smoke, opium.

Clinical Presentation

Early symptoms subtle; site not routinely inspected → delayed diagnosis.
Four major symptom clusters:

1. Nasal (≈ $80\%$ of cases)

• Persistent mucoid/purulent discharge.
• Episodic epistaxis.
• Unilateral/bilateral nasal obstruction; hyponasal ("stuffy") speech.
• Altered olfaction.

2. Otologic

• Conductive hearing loss, aural fullness, tinnitus.
• Serous otitis media (from ET obstruction).

3. Ophthalmo-neurologic

• Headache, facial/retro-orbital pain.
• Cranial nerve (CN) deficits: V (reduced corneal reflex), III/IV/VI (diplopia, ophthalmoplegia, proptosis), II (vision loss).
• Advanced skull-base spread → CN IX–XII palsies, trismus (pterygoid involvement), Horner’s syndrome.

4. Cervical Nodal Metastasis

• Often first clinical sign; upper-jugular & posterior-triangle nodes.
• Retropharyngeal nodes palpable internally.

Path of spread summary (slide diagram):

Tumour invades parapharyngeal space → foramen lacerum/ovale → cranial base.
Distant metastases: lung, liver, bone.

Diagnostic Approach

Comprehensive history + ENT examination with rigid/flexible nasoendoscope.
Any neck node of unknown primary ⇒ mandatory nasopharyngeal inspection & biopsy.

Work-Up

Labs: full blood count, chemistry; EBV serology (IgA/IgG-VCA, EA).
Imaging
• CT head/neck: primary size, skull-base erosion, neck nodes.
• MRI: superior for intracranial and parapharyngeal extension.
• Bone scan: osseous metastasis.
• Chest radiograph (CXR): pulmonary spread.
Procedures: endoscopic biopsy of primary (local anaesthesia) OR open biopsy of metastatic neck node (gold standard).

Histology (WHO Classification)

Type I : keratinising squamous cell carcinoma.
Type II : differentiated non-keratinising carcinoma.
Type III: undifferentiated non-keratinising carcinoma.
• Types II & III = endemic forms, closely EBV-associated; typically more radiosensitive.

Staging Systems (several co-existing)

American Joint Committee on Cancer (AJCC).
International Union Against Cancer (UICC).
Ho classification (historical).

Treatment Modalities & Principles

Goals: cure when possible; palliation for advanced/metastatic disease.
Multidisciplinary team: ENT/head-neck surgeon, clinical/radiation oncologist, radiologist, pathologist, specialist nurses, dietician.

Radiotherapy (RT)

Cornerstone & primary modality for loco-regional control.
Indicated for stages $I\text{–}IV_{\text{B}}$ (all but distant metastasis only).
Technique: high-energy external beam (conformal/IMRT).
Dose: $65\text{–}70\,\text{Gy}$ to primary & involved nodes, fractionated.

Chemotherapy (CT)

Enhances control in advanced loco-regional disease.
Timing options: neoadjuvant (induction), concurrent (chemoradiation), adjuvant (post-RT).
Active agents: cisplatin, $5$ -fluorouracil, doxorubicin, epirubicin, bleomycin, mitoxantrone, methotrexate (Al-Sarraf protocol et al.).

Surgery

Limited role ➔ chiefly diagnostic & salvage.
Indications
• Endoscopic biopsy of primary / neck node.
• Neck dissection for persistent/recurrent nodal disease after RT/CT.
• Tracheostomy for airway compromise.
• Nasopharyngeal access for brachytherapy implantation or local excision in highly selected cases.
• Emerging skull-base resections (rare, specialised centres).

Follow-Up Strategy

Essential for detecting recurrence, radiation complications, functional rehab.
Schedule
• Every $2\text{–}3$ months during first $3$ years.
• Every $6$ months in $4^{\text{th}}$ & $5^{\text{th}}$ year.
• Annually until at least $7$ years post-therapy.
Multidisciplinary: oncologist, head-neck surgeon, speech therapist, dentist.

Key Take-Home Points / Conclusion

Nasopharynx’s deep location hides early tumours → high index of suspicion required.
NPC is rare worldwide but common in certain ethnic/geographic groups; EBV & salted-fish exposure hallmark risks.
Presentations include nasal, aural, neurologic and neck mass symptoms; clinicians must inspect nasopharynx in any cervical node of unknown origin.
Types II/III non-keratinising tumours highly radiosensitive; combined chemoradiation provides best outcomes; surgery reserved for biopsy/salvage.

Selected References (as cited in lecture)

Breda E. et al. (2010) EBV detection in NPC, Braz J Otorhinolaryngol.
Hila L. et al. (2009) Tunisian epidemiology of NPC, Pathol Biol.
Larsen-Reindorf R. et al. (2014) Head & neck cancers in Ghana, Int J Otorhinolaryngol Head Neck Surg.
Ayee R. et al. (2020) EBV genotypes in Ghanaian NPC patients, Viruses.
Cummings Otolaryngology (textbook).
Dawson C.W., Port R.J., Young L.S. (2012) Role of EBV LMP1/2, Seminars in Cancer Biology.
Jiang Q. et al. (2016) miR-16 & CDK4 knockdown in NPC, Tumor Biol.
Zhang X. et al. (2014) Genetic variants PTEN/AKT1/MDM2/p53 in NPC, PLoS ONE.