Nasopharyngeal Carcinoma

Is screening necessary?

by Dr Valerie Tay

Nasopharyngeal carcinoma (NPC) of the undifferentiated subtype is endemic to southern China, Hong Kong and Singapore.

Current therapeutic decisions are based mainly on disease stage, and patient prognosis has improved significantly over the past 30 years because of advances in imaging, technology in delivery of irradiation, and broader application of chemotherapy.

Pathology

Table 1. WHO classification

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Type 2b accounts for >95% of NPC cases in endemic regions mention above, and 25% to 60% in non-endemic regions.

Epidemiology and risk factors

NPC is most common in regions of Southern China (25 to 40 per 100,000 population), Hong Kong and Singapore.

Based on the statistics from the Singapore Cancer Registry, nasopharyngeal carcinoma incidence is 11.8 per 100, 000 male population, ranking number 8 out of the 10 most frequent cancers in males (between 2010 and 2014).

Unlike other squamous cell cancers of the head and neck, nasopharyngeal cancer does not appear to be linked to excess use of tobacco or moderate alcohol intake.

Family history is a strong risk factor for NPC, where there is a 4- to 8-fold risk if the patient has a first degree relative with NPC.

Signs and symptoms

One would often think that the most likely symptom for a cancer involving the nasopharynx, which is the posterior most aspect of the nose, is epistaxis.

However, cervical lymph node enlargement is the most common presenting symptom.

List of common signs and symptoms

• Painless, enlarged neck nodes (present in approximately 75% of patients and often bilateral and posterior).

• Blood-stained saliva, especially when hawking mucus from the nasopharynx.

• Otitis media with effusion, especially if unilateral.

• Cranial nerve dysfunction (especially V, VI and XII).

Should screening be done?

Many laboratories offer EBV IgA serology as a cancer marker for NPC. However, according to the Cochrane Ear, Nose and Throat Disorders Group report no data from RCTs or CCTs are available to allow us to determine the efficacy of screening for nasopharyngeal cancer.

Clinical Practice Guidelines published by the Ministry of Health in 2010 states that mass screening of general population at normal risk with EBV serology is not recommended. However, families with two or more index cases of NPC may be screened with EBV IgA (VCA and EA) and nasolaryngoscopy. The kits are available commercially using ELISA methods for measuring IgA to EBV EA, EBNA-1 are of uncertain clinical viability, but indirect immunofluorescence tumour marker to measure IgA to EBV VCA and EA would be more clinically useful.

Diagnostic tests

As the nasopharynx is not accessible except by nasolaryngoscopy, diagnosis is made by performing an in-office scope and biopsy of the nasopharyngeal mass, usually under local anaesthetic. Other examination and tests include:

• Documentation of the size and location of the tumour and neck nodes

• Evaluation of cranial nerve function

• Computed tomographic (CT) scan or positron emission tomography (PET)-CT scan

• Magnetic resonance imaging (MRI) to evaluate skull base invasion

• Epstein-Barr virus DNA titres for evaluation of response to therapy and relapse

Stage information and treatment

Treatment is given according to the American Joint Committee on Cancer (AJCC) TNM classification for nasopharyngeal cancer.

Stage 1: High-dose radiation therapy (RT) to the primary tumour site and prophylactic radiation therapy to the neck.

Intensity modulated RT (IMRT) is the current standard of treatment for NPC. High-dose radiation is tailored for complete coverage of tumour targets while sparing the normal structures, resulting in a significant reduction in the risk of complications such as permanent xerostomia.

Stage 2: Radiation alone or concurrent chemoirradiation followed by adjuvant chemotherapy

Stage 3: Concurrent chemo-irradiation followed by adjuvant chemotherapy. Another option that is also being studied is neoadjuvant chemotherapy – where chemotherapeutic drugs given prior to radiotherapy has been shown to shrink tumours, which renders them more treatable with radiation.

Stage 4: Chemoirradiation therapy followed by adjuvant chemotherapy, or neoadjuvant chemotherapy. Chemotherapy alone for metastatic disease.

For all treatment modalities, surgery (neck dissection) is performed for residual nodal disease.

Prognosis

Five-year disease-specific survival rates for stage I to II disease are in the region of 94% to 97% based on some retrospective studies.

For stage III and IV disease, the use of induction chemotherapy in some clinical trials has shown to improve 3-year progression free survival, 64% to 88%.

Summary

NPC of the undifferentiated subtype is endemic in our country. There is significant risk in patients who have first degree relatives diagnosed with the disease, and they should be screened regularly with nasolaryngoscopy and EBV serology. The general population with normal risk should not be screened for NPC. Patients with painless, enlarged neck nodes and blood in saliva should raise suspicion for NPC, and diagnosis is achieved by a biopsy with nasolaryngoscopy.

References:

• Vasef MA, Ferlito A, Weiss LM. Nasopharyngeal carcinoma, with emphasis on its relationship to Epstein-Barr virus. Ann Otol Rhinol Laryngol. 1997;106(4):348-356.

• Guo X, Johnson RC, Deng H, et al. Evaluation of nonviral risk factors for nasopharyngeal carcinoma in a high-risk population of Southern China. Int J Cancer. 2009;124(12):2942-2947.

• Ng WT, Choi CW, Lee MC, et al. Outcomes of nasopharyngeal carcinoma screening for high risk family members in Hong Kong. Fam Cancer. 2010 ;9(2):221-228.

• Chan ATC. Nasopharyngeal Carcinoma. Ann Oncol. 2002;13:1007-1015.

• Sanguineti G, Geara FB, Garden AS, et al. Carcinoma of the nasopharynx treated by radiotherapy alone: determinants of local and regional control. Int J Radiat Oncol Biol Phys. 1997;37(5):985-996.

• Langendijk JA, Leemans CR, Buter J, et al. The additional value of chemotherapy to radiotherapy in locally advanced nasopharyngeal carcinoma: a meta-analysis of the published literature. J Clin Oncol. 2004;22(22):4604-4612.

• Huncharek M, Kupelnick B. Combined chemoradiation versus radiation therapy alone in locally advanced nasopharyngeal carcinoma: results of a meta-analysis of 1,528 patients from six randomized trials. Am J Clin Oncol. 2002;25(3):219-223.

• Al-Sarraf M1, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998;16(4):1310-1317.

• Lee AW, Ma BB, Ng WT, et al. Management of Nasopharyngeal Carcinoma: Current Practice and Future Perspective. J Clin Oncol. 2015;33(29):3356-3364.

• Lee AW, Ng WT, Chan LL, et al. Evolution of treatment for nasopharyngeal cancer–success and setback in the intensity-modulated radiotherapy era. Radiother Oncol. 2014;110(3):377-384.

• Ng WT1, Chang AT, Lee SW, et al. Chemotherapy for Nasopharyngeal Cancer: Neoadjuvant, Concomitant, and/or Adjuvant. Curr Treat Options Oncol. 2015;16(9):44.

author
Dr Valerie Tay is the medical director and consultant otorhinolaryngology (Ear, Nose & Throat) of SMG ENT Centre, a Singapore Medical Group clinic. Dr Tay specialises in ENT – covering all aspects including rhinology, sleep, head and neck and facial plastic surgery. To hone her interest in Facial Plastic Surgery, she completed a one year fellowship in a world renowned and high volume plastic surgery clinic in Seoul, Korea.
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