Step 1 of 14
High-Risk Recognition & Red-Flag Symptoms
Ethnic/EBV/dietary risk + nasal · otologic · neck · neurological · constitutional clusters
Nasopharyngeal carcinoma is suspected from the combination of risk profile and symptom cluster, because the nasopharynx is silent and disease presents late. The epidemiologic risks are Southern Chinese, Southeast Asian, Arctic Inuit, and North African ancestry, a family history of NPC, male sex, age 30–60, Epstein–Barr virus exposure, a salted-fish / nitrosamine-rich diet in childhood, tobacco use, and occupational wood-dust or formaldehyde exposure.
The symptom clusters that should trigger nasopharyngeal evaluation are nasal (unilateral obstruction, recurrent epistaxis, blood-stained postnasal discharge), otologic (adult unilateral middle-ear effusion, Eustachian-tube dysfunction, conductive hearing loss, aural fullness), neck (painless cervical lymphadenopathy, classically bilateral upper-neck nodes), neurological (persistent headache, diplopia, facial numbness or pain, dysphagia, hoarseness — signalling skull-base spread), and constitutional (weight loss, fatigue, bone pain). The unilateral middle-ear effusion and the upper-neck node are the two presentations most often missed.
- Risk — Southern Chinese / SE Asian / Inuit / N African ancestry, family history, male, EBV, salted-fish diet
- Nasal — unilateral obstruction, recurrent epistaxis, blood-stained postnasal discharge
- Otologic — adult unilateral middle-ear effusion, Eustachian dysfunction, conductive hearing loss
- Neck — painless cervical (bilateral upper-neck) lymphadenopathy — often the first sign
- Neurological / constitutional — headache, diplopia, facial numbness, dysphagia; weight loss, bone pain
Key statistics
Endemic NPC incidence
~20–30 / 100,000 (S China)
In endemic Southern China the age-standardised incidence reaches roughly 20–30 per 100,000, versus under 1 per 100,000 in non-endemic regions — among the most geographically concentrated of all cancers, and almost entirely EBV-driven.
★ High-yield pearls (chapter-wide)
- An adult with a persistent unilateral middle-ear effusion has NPC until nasopharyngoscopy and MRI say otherwise — never just grommet a one-sided adult glue ear.
- Bilateral or upper-neck (level II/retropharyngeal) painless lymphadenopathy in an at-risk adult is a classic NPC presentation — the neck node is often the first sign.
- Multiple cranial neuropathies point to skull-base and cavernous-sinus invasion — assume skull-base involvement and get urgent MRI.
- The retropharyngeal (Rouvière) node is the first nodal station and is not palpable — MRI assessment is mandatory, not optional.
- Plasma EBV DNA is the chapter's biomarker — high pre-treatment levels predict larger burden, metastasis, and worse outcome; a rising level on follow-up signals recurrence before imaging.
- WHO type III (non-keratinizing undifferentiated) is the commonest, most EBV-associated, and most radiosensitive subtype in endemic regions.
- NPC is a non-surgical primary — radiotherapy (IMRT) is the backbone, with chemotherapy added by stage; surgery is reserved for salvage of residual or recurrent disease.
- Optimise before you irradiate — dental clearance prevents osteoradionecrosis, baseline audiology precedes cisplatin, and nutrition support precedes chemoradiotherapy.
- Stage drives treatment: I → IMRT alone; II → concurrent chemoradiotherapy; III–IVA → induction chemotherapy then concurrent chemoradiotherapy; IVB/metastatic → systemic therapy with immunotherapy.
- Small central recurrences are increasingly salvaged by endoscopic nasopharyngectomy, which can outperform re-irradiation by avoiding its severe late toxicity.
Evidence base
3 sources- HIGH
Chen YP, Chan ATC, Le QT · Lancet · 2019Seminal reviewPMID 31178151
Authoritative Lancet review of NPC — anchors epidemiology, EBV biology, staging, and stage-directed management throughout the chapter.
- HIGH
Bossi P, Chan AT, Licitra L · Ann Oncol · 2021Clinical practice guidelinePMID 33358989
ESMO-EURACAN guideline — the European reference standard for NPC diagnosis, treatment, and follow-up.
- HIGH
Chan KCA, Woo JKS, King A · N Engl J Med · 2017Screening cohortPMID 28792880
NEJM screening study showing plasma EBV DNA detects early, curable NPC in asymptomatic endemic populations.
Decision tree
The triage screen is the first gate. Classification routes the stable patient to one of the aetiology-keyed pathways below. Cross-cut cards capture the chapter's must-not-miss rules.