This document provides an overview of nasopharyngeal carcinoma (NPC), including its epidemiology, etiology, histological classification, clinical features, diagnosis, staging, treatment and prognosis. NPC has a unique geographical and ethnic distribution. It is caused by an interaction between genetic factors, Epstein-Barr virus infection and environmental exposures. Diagnosis involves biopsy of suspicious nasopharyngeal lesions. The main treatment is radiotherapy, while chemotherapy may be added for advanced cases. Prognosis depends on stage, with 5-year survival rates ranging from 80-90% for early stage to 20-40% for stage IV disease.

1. Nasopharyngeal carcinoma
Nasopharyngeal carcinoma has preculiar geographical & ethnic variation in its occurance. It is a
disease surrounded by controversy; from pathogenesis to histopathology, disease staging & related
management strategies. Thus ,in many ways ,NPC differs from other head neck cancer.
Epidemiology
a) Edemic NPC (WHO type II & III, Its incidence starts rise after second decade & slowly
reaches a plateau for both sexes. After the fifth decade then gradually drops with increasing
age. Below the age of 50 year, the incidence of NPC is higher than any other cancer.
--found predominantly in the southern province of china ,southeast asia, certain
Mediterranean populations.
--Risk factors include EBV, genetic predispositions (HLA class I & II halplotype),environmental
factors (food –preserving nitrosamine frequently used salted fish).The incidence of NPC
among Chinese born in north America is significantly lower than among native –born
Chinese but still greater than the risk for Caucasians ,emphasizing a synergistic role of
environmental factors.
b) sporadic NPC (WHO type –I): a bimodal age distribution (below the age 16 & above 50-59)
related to tobacco & alcohol exposure.
Aetiology of NPC
The development of nasopharyngeal carcinoma is the result of a complex interplay of genetic
factors, early latent infection by EBV & its reactivation, &exposure to environmental carcinogens.
1)Genetic factors;
The human leucocyte antigen (HLA) ; the loci involved are the HLA –A,B& DR located on the short
arm of chromosome 6.
2)EBV; EBV is a double –stranded DNA virus that is part of human herpes virus family,It establishes
persistent ,chronic infection, usually in B lymphocytes. Six nuclear proteins & three membrane
proteins are believed to mediate EBV-related carcinogen.
EBV antibodies are acquired earlier in life in tropical countries but adulthood 90-95% of population
have EBV antibody.
EBV is detected in virtually all patients with NPC.
B-cell lymphocyte should serve as the only reservoir of EBV & persistent infection within epithelial
cells strongly suggests premalignancy or NPC.
Nasopharyngeal brush biopsy or swab has been advocated for sceening & early diagnosis by using
polymerage chain reaction(PCR) to detect the EBV genome with nasopharyngeal epithelia.

2. 3)Environmental carcinogens;
Numerous environmental agents including dust , household smoke,industrial fumes & tobacco
smoke.
Diet containing high salted fish & low in vitamin-rich fresh vegetables & fruits. High salted fish
contains nitrosamines.
Immunology & serology;
EBV is a ubiquitous human herpes virus(nick name Every Body’s virus).Primary EBV infection usually
occurs early in life & is largely asymptomatic.If primary EBV infection is delayed until adolescence
,the clinical symptom of infectious mononucleosis. Primary infection causes permanent immunity &
also life –long virus persistence.
The anti-EBV serological response particularly IgA.IgA aganist viral capsid antigen(VCA) &early
antigen(EA) with NPC.
The IgA anti-VCA appear to be more sensitive but less specific than IgA anti-EA.These antibody are
extremely useful in screening high risk populations for NPC.
Histological classification
a) Type –I Keratinizing SCC, similar to other SCC of head & neck.
-well differentiated
-moderately differentiated
-poorly differentiated
b)Type –II, Nonkeratinizing SCC.
c) Type-III , undifferentiated carcinoma. Known as lymphoepithelioma.
Clinical features
An early tumour may cause no symptoms ,even if it does,symptom of early NPC are often trifling &
nonspecific& tend to ignored by both Doctors & patients.
Cervical lymphadenopathy is the commonest presenting symptom of NPC & typically situated in the
upper part of the posterior triangle. Overall 75% of the patients have palpable cervical
lymphadenopathy.
Nasal symptom (30%); blood staining discharge, nasal obstruction, post nasal drip, or even epistaxis.
Aural symptom (20%); hearing impairment, tinnitus, otalgia, OME is very common clinical finding.
(tumour infiltrating the Eustachian tube musculature).
Neurological manifestations comprise headache & cranial nerve involvement. Cranial involvement
indicate advance disease, tumour spread through foramina of base of skull (V & VI are common ) &
orbital involvement (III &IV) or parapharyngeal space involvement(last four cranial nerve).

3. Trimus with direct involvement of the pterygoid muscle.
Systemic metastasis at presentation are rare.
Diagnosis of NPC
History & examination
Obvious tumour normal looking NP
biopsy NP(L/A Clinically suspicious Clinically not suspicious
NPC, Diagnosis uncertain, others diagnosis Follow up
Treatment, repeat biopsy, others treatment.
Radiologically suspicious, unexplained SOM, persistently raised IgA, Suspicious neck node
FNAC
Biopsy NP under G/A
Hitory:
The presenting symptoms are diverse & nonspecific, if present are usually related to the ear the
unexplained , especially if unilateral.
Examination:
1) PNS mirror examination;
2) Transoral retrograde nasopharyngoscopy with 700 or 900 endoscope gives best possible
view of the nasopharynx. As the view obtained is from below & behind ,fossa of Rosenmuller
are wide open foe evauation,allowing even minute degrees of asymmetry between the two
sides to be identified.
On rare occasion ,tumour may remain submucosal in the nasopharynx& only become obvious
after reaching the nasal fossa.

4. 3) Antegrade nasopharyngoscopy ;Flexible fibrescopy (3.5 or 3.7mm) or Rigid endoscope (4mm
,00 & 300 Hopkins rod).
The view of the nasopharynx obtained with the antegrade approach is from front to back.
Thus depths of the fossae of Rosenmullar will be hidden by the inwardly projecting
Eustachian cushions.
A simple maneouvre by asking the patient to say ‘ah’ mouth sound & ‘ng’ nasal sound.&
then to swallow (opening & closing the Eustachian tube) will expose any small lesion in the
fossae of Rosenmuller for inspection.
Biopsy of the nasopharynx
Biopsy of the nasopharynx is considered the first investigation for NPC if suspicious lesion is found.
Ideally ,this should be carried out during the patient’s first OPD visit. Biopsy is carried out under L/A.
The endoscope should be passed the floor of the nose leaving the ipsilateral side of the tumour &
biopsy forecp (Takahashi biopsy forcep) pass through floor of the nose, the ipsilateral side of the
tumour. Flexible endoscope is not recommened as the tiny forceps provide an inadequate tissue
sample for diagnosis.
When previous biopsy is inconclusive, examination &biopsy should be taken under G/A. Multiple
deep biopsy from centre of the nasopharynx & fossa of Rosenmullar of the both side.
Differential Diagnosis
Rhinosinusitis or nasal polyps may coexist with NPC.
Delay in diagnosis
NPC is extremely radiosensitive & readily curable if diagnosis is made in early stage.only 10 % of
cases are diagnosed early stage.
The absence of ,or the trifling nature of ,symptoms of early NPC is the leading cause to delayed
diagnosis.More over patient with NPC are mostly young ,healthy & fit.
Other diagnostic tools
The key to diagnosis of NPC is to have an accurate biopsy & histological examination ,95% cases will
be diagnosed . In atypical cases where the disease is submucosal or biopsy is negative additional
investigation are indicated.
Serology
The detection of IgA antibody to the EBV specific antigens is helpful in the diagnosis of NPC.
The IgA anti –VCA titre is high,although lacking in specificity especial in low level.
The IgA anti –EG titre is less sensitive but specificity is extremely high.

5. Imaging;
Although imaging may occasionally be needed to identify the site of submucosal tumour, tumour
staging, radiotherapy planning & post-operative monitoring.
MRI is the most accurate method of evaluating the primary tumour.
1),It accurately differentiate parapharyngeal space distortion by the tumour.
2) Explain direct perineural spread of tumour.
3)The additional view in the sagital plain improves assessment of the clavius&
4) Better define nodal metastasis.
PET( 18 fluro-deoxyglucose)
Functional scanning with the ability to differentiate hypometabolic (post-RT oedema ) from
hypermetablic (viable cancer tissues) is a useful adjunct to the conventional imaging technique.
Staging
AJCC stage classification for NPC.
TX primary tumour cannot be assessed.
T0 No evidence of the tumour.
Tis Carcinoma in situ.
T1 Tumour confined to the nasopharynx.
T2 Tumour extends to the oropharynx , nasal cavity &parapharyngeal extension.
T3 Tumour involves bony structures and/or paranasal sinuses.
T4 Tumour with intracranical extension and/or involvement of cranial nerves,infratemporal
Fossa, hypopharynx, orbit or masticator space.
Treatment
NPC is an extremely radiosensitive tumour & mainstay of treatment for primary local &regional
disease.For patients with advanced disease, the addition of chemotherapy appears to enhance the
overall treatment results. Surgery,at present is only used to salvage local & regional failures.
Radiotherapy
Megavoltage external radiotherapy (ERT) is the primary treatment modality of choice.This is given
through two lateral opposing & one anterior field. The field design is the whole nasopharynx & both
side of the neck.Elective neck irradiation is practised whole wide due to high incidence of occult
nodal metastases.

6. Chemotherapy;
Chemotherapy is describe as neoadjuvant ,concurrent or adjuvant to radiotherapy.
Neoadjuvant chemotherapy used to reduce the size of bulky neck nodes so that the standard
radiotherapy can be applied.
Concurrent (cisplatin) chemoradiation , a significant short term progression free survival benefit..
Follow up plan
After primary treatment ,patients should be seen at least two monthly for the 1year, three
monthly for 2nd & 3rd year. Six-monthly thereafter lifelong.
Repeated nasoendoscopy is best follow up .
Post-treatment biopsy is indicated if there is any residual disease at primary site.
Imaging is needed to evaluate regional disease.
CXR – every year to see the chest metastases.
Salvage treatment
Local persistence ; positive biopsy at various time intervals after primary treatment & residual
tumour will become truely persistent & not regress. A further dose of ERT may be possible.
Brachytherapy is preferred over standard ERT.
Local recurrence; Re-irradiation has been commonest method to treat local recurrence.
Surgical salvage for local disease; surgical approach to the nasopharynx;
1) Anterior approaches;
Lateral rhinotomy
Transnasal transmaxillary
Midfacial degloving
Le Fort I osteotomy
Maxillary swing
2) Inferior approach
Transpalatal
Mandibular swing
3) Lateral approach ; through infratemporal fossa.

7. Surgical salvage for neck disease
Radical neck dissection (RND).
Prognosis
The average 5 years survival by conventional ERT for early disease 80-90%. (stage –I)
Stage –II 70-80%
Stage III 40-60%
StageIV 20-40%
Complications of ERT
Complications are acute ,subacute & late.
Acute;
Xerostomia
Oropharyngeal mucositis
Altered taste sensation
Dermitis
Alopecia
Subacute ;25-30%
OME: the treatment of OME should be conservative.Use of grommet during & after ERT associated
with otorrhoea &otalgia.
Olfactory dysfunction is transient.
Nasal crusting; regular saline douching in the first few years after ERT with antibiotic may be
adequate control.
Rhinosiusitis ; Thick nasal catarrh & foul smelling nasal discharge.
Late ; complications vary from several years to many years after ERT. 30%
Occur that have poor power of regeneration. Neural tissues.
Trismus & neck stiffness due to soft tissues fibrosis.
Osteonecrosis of anterior & lateral skull base.
Hypothalamic-pituitary dysfunction.
Temporal lobe necrosis ; epileptic fit.
Last four cranial nerve palsies; hypoglossal nerve most common.

8. Osteosarcoma of nasal & sinus bone.
SCC of oral cavity & pharynx.