- History, Physical Exam, and Endoscopy
- Complete H&P including full head and neck exam, with mirror examination as clinically indicated:
- Nasopharyngeal fiberoptic examination
- Documentation of tobacco (pack-years) and alcohol use with cessation counseling:
- Distress screening
- Complete H&P including full head and neck exam, with mirror examination as clinically indicated:
- Tissue Diagnosis
- Biopsy of primary site or FNA of the neck:
- Image-guided (US or CT) needle biopsy of cystic neck nodes may improve yield over palpation-guided FNA
- Core biopsy preferred when systemic therapy is planned for unresectable / metastatic disease:
- Allows biomarker testing
- Biopsy of primary site or FNA of the neck:
- Imaging of Primary and Neck
- MRI with and without contrast from skull base to clavicle, ± CT skull base/neck with contrast
- MRI preferred for:
- Skull base invasion, cranial nerve involvement, perineural spread, intracranial / orbital extension, marrow invasion
- CT complementary for cortical bone erosion / destruction
- MRI preferred for:
- MRI with and without contrast from skull base to clavicle, ± CT skull base/neck with contrast
- Imaging for Distant Metastases
- FDG-PET / CT and / or chest CT with contrast:
- Bone scan if PET / CT not done
- FDG-PET/CT preferred for locoregionally advanced disease (T3 to T4 or ≥ N1)
- Dedicated contrast-enhanced brain MRI:
- Reserved for histologies where brain metastasis is a concern
- FDG-PET / CT and / or chest CT with contrast:
- Virology and Biomarkers
- EBV / DNA testing:
- For nonkeratinizing or undifferentiated histology:
- Test tumor tissue and blood
- For nonkeratinizing or undifferentiated histology:
- Tissue:
- ISH for EBV-encoded RNA (EBER) or IHC for latent membrane protein (LMP)
- Blood:
- Plasma / serum EBV DNA load by PCR (BamHI-W, EBNA, or LMP targets):
- Reflects prognosis and treatment response
- Plasma / serum EBV DNA load by PCR (BamHI-W, EBNA, or LMP targets):
- Consider HPV testing (may inform etiology)
- EBV / DNA testing:
- Additional Evaluations as Clinically Indicated
- Dental / prosthodontic evaluation
- Nutrition, speech, and swallowing evaluation/therapy
- Audiogram
- Consideration of ophthalmologic and endocrine evaluation
- Fertility / reproductive counseling
- Screening for hepatitis B
- Multidisciplinary consultation
- Staging
- Clinical staging follows AJCC / UICC TNM (9th ed.):
- Distinct from other head and neck subsites:
- Nodal criteria use a 6-cm size cutoff and the caudal border of the cricoid cartilage as a landmark
- T0 defined by EBV-positive cervical nodes without identifiable primary
- Workup culminates in classification into M0 vs M1 pathway
- Distinct from other head and neck subsites:
- Clinical staging follows AJCC / UICC TNM (9th ed.):
- Key Practical Points
- Endoscopy plus biopsy is the diagnostic gold standard:
- Most tumors arise in the fossa of Rosenmüller:
- Targeted / blind biopsies appropriate:
- When no tumor is visible but suspicion is high
- Targeted / blind biopsies appropriate:
- Most tumors arise in the fossa of Rosenmüller:
- MRI is the preferred modality for local staging:
- Reported 100% sensitivity, 84% specificity in one series
- FDG-PET / CT is the most sensitive test for nodal and distant metastasis
- Plasma EBV DNA is more sensitive / specific than serum IgA / VCA titers:
- Correlates with stage, and normalizes with successful treatment:
- Useful for baseline risk stratification and post-treatment monitoring
- Correlates with stage, and normalizes with successful treatment:
- WHO histology:
- Keratinizing SCC
- Nonkeratinizing carcinoma:
- Differentiated
- Undifferentiated:
- Lymphoepithelioma-like carcinoma is a variant of the undifferentiated type
- Basaloid SCC
- In non-endemic regions:
- A larger fraction of NPC is EBV-negative:
- More often keratinizing / HPV-associated):
- Lowering EBV DNA diagnostic yield
- More often keratinizing / HPV-associated):
- A larger fraction of NPC is EBV-negative:
- Endoscopy plus biopsy is the diagnostic gold standard:
- References
- Head and Neck Cancers. National Comprehensive Cancer Network. Updated 2026-05-12.
- ACR Appropriateness criteria® for nasopharyngeal carcinoma. Saba NF, Salama JK, Beitler JJ, et al. Head & Neck. 2016;38(7):979-86. doi:10.1002/hed.24423.
- Nasopharyngeal Carcinoma. Chua MLK, Wee JTS, Hui EP, Chan ATC. Lancet (London, England). 2016;387(10022):1012-1024. doi:10.1016/S0140-6736(15)00055-0.
- The Role of Cross-Sectional Imaging in Suspected Nasopharyngeal Carcinoma. Shayah A, Wickstone L, Kershaw E, Agada F. Annals of the Royal College of Surgeons of England. 2019;101(5):325-327. doi:10.1308/rcsann.2019.0025.
- Nasopharyngeal Carcinoma. Chen YP, Chan ATC, Le QT, et al. Lancet (London, England). 2019;394(10192):64-80. doi:10.1016/S0140-6736(19)30956-0.
- Comparison of Plasma Epstein-Barr Virus (EBV) DNA Levels and Serum EBV Immunoglobulin a/Virus Capsid Antigen Antibody Titers in Patients With Nasopharyngeal Carcinoma. Shao JY, Li YH, Gao HY, et al. Cancer. 2004;100(6):1162-70. doi:10.1002/cncr.20099.
- Epstein-Barr Virus DNA in Nasopharyngeal Carcinoma: A Brief Review. Xue F, He X. Methods in Molecular Biology (Clifton, N.J.). 2020;2204:99-107. doi:10.1007/978-1-0716-0904-0_9.
- Circulating Tumor DNA in Head and Neck Cancer. Kansara S, Contrera K, Roof S, et al. JAMA Otolaryngology– Head & Neck Surgery. 2026;:2851926. doi:10.1001/jamaoto.2026.2045.
Rodrigo Arrangoiz MS, MD, FACS, FSSO 