Nasopharyngeal carcinoma (NPC) is a tumor arising from the epithelial cells that cover the surface and line the nasopharynx. NPC was first described as a separate entity by Regaud and Schmincke in 1921 1 2 . Approximately one third of nasopharyngeal carcinomas of the undifferentiated type are diagnosed in adolescents or young adults. Although rare, NPC accounts for one third of childhood nasopharyngeal neoplasms (data from USA) 3 .

The annual incidence of NPC in the UK is 0.25 per million (age standardized, age 0–14 years), 0.1 per million at age 0–9 years and 0.8 per million at age 10–14 years. It seems reasonable to assume, on the basis of England and Wales cancer registry data, that at least 80% of nasopharyngeal cancers at age 15–19 years are carcinomas. This suggests an incidence of 1 to 2 per million for NPC at age 15–19 years.

In comparison with other countries, the incidence in the UK is low. In particular, in Tunisia the incidence is relatively high 4 . In southern parts of China, Southeast Asia, the Mediterranean basin and Alaska the incidence of NPC is moderately elevated; an incidence of 2 per million of NPC in China has been reported 5 . In other countries, for example in India, the incidence is comparable to that in the UK at 0.9 per million. Furthermore, the younger age peak in the second decade found in India 6 , is also found in the UK 7 .

NPC is the commonest epithelial cancer in adults. The detection of nuclear antigen associated with Epstein-Barr virus (EBNA) and viral DNA in NPC type 2 and 3, has revealed that EBV can infect epithelial cells and is associated with their transformation 8 . The etiology of NPC (particularly the endemic form) seems to follow a multi-step process, in which EBV, ethnic background, and environmental carcinogens all seem to play an important role.

Lo et al. showed that EBV DNA was detectable in the plasma samples of 96% of patients with non-keratinizing NPC, compared with only 7% in controls 9 . More importantly, EBV DNA levels appear to correlate with treatment response 9 10 11 and they may predict disease recurrence 11 , suggesting that they may be an independent indicator of prognosis 12 .

In adults, other likely etiological factors include genetic susceptibility, consumption of food (in particular salted fish) containing carcinogenic volatile nitrosamines, and as in children, EBV 13 15 16 17 18 19 .

NPC usually originates in the lateral wall of the nasopharynx, which includes the fossa of Rosenmuller. It can then extend within or out of the nasopharynx to the other lateral wall and/or posterosuperiorly to the base of the skull or the palate, nasal cavity or oropharynx. It then typically metastases to cervical lymph nodes. Distant metastases may occur in bone, lung, mediastinum and, more rarely, the liver.

Cervical lymphadenopathy is the initial presentation in many patients, and the diagnosis of NPC is often made by lymph node biopsy. Symptoms related to the primary tumor include trismus, pain, otitis media, nasal regurgitation due to paresis of the soft palate, hearing loss and cranial nerve palsies. Larger growths may produce nasal obstruction or bleeding and a "nasal twang". Metastatic spread may result in bone pain or organ dysfunction. Rarely, a paraneoplastic syndrome of osteoarthropathy may occur with widespread disease.

Three subtypes of NPC are recognized in the World Health Organisation (WHO) classification 20 :

• type 1: squamous cell carcinoma, typically found in the older adult population

• type 2: non-keratinizing carcinoma

• type 3: undifferentiated carcinoma

Most cases in childhood and adolescence are type 3, with a few type 2 cases 21 . Type 2 and 3 are associated with elevated Epstein-Barr virus titers, but type 1 is not 22 . The Cologne modification of the WHO scheme by Krueger and Wustrow 23 includes the degree of lymphoid infiltration. Types 2 and 3 may be accompanied by an inflammatory infiltrate of lymphocytes, plasma cells, and eosinophils, which are abundant, giving rise to the term lymphoepithelioma. Two histological patterns may occur: Regaud type, with a well-defined collection of epithelial cells surrounded by lymphocytes and connective tissue, and Schmincke type, in which the tumor cells are distributed diffusely and intermingle with the inflammatory cells. Both patterns may be present in the same tumor.

Diagnostic methods include:

1. Clinical evaluation of the size and location of cervical lymph nodes.

2. Indirect nasopharyngoscopy to assess the primary tumor.

3. Neurological examination of cranial nerves.

4. Computed tomography (CT)/magnetic resonance imaging (MRI) scan of the head and neck to below clavicles to assess base of skull erosion.

5. Chest radiotherapy (anteroposterior and lateral) to see if NPC has spread to the lungs.

6. Bone scintigraphy by Tc 99 diphosphonate to show whether cancer has spread to the bones.

7. Full blood count.

8. Urea, electrolyte, creatinine, liver function, Ca, PO₄, alkaline phosphate.

9. EBV viral capsid antigen and EBV DNA.

10. Biopsy of either the lymph nodes or primary tumor for histological examination.

The tumor, node, metastasis (TNM) classification of the American Joint Committee on Cancer 24 – sixth edition (Table 1) is usually used to determine the tumor staging (Table 2). This latest TNM classification takes into account Ho's 25 modifications for NPC, which utilizes the prognostic importance of affected nodes extending into the lower cervical and supraclavicular areas.

Presentation with lymphadenomegalia implies that the disease has spread beyond the primary site. However, in childhood the presence of metastatic disease in cervical lymph nodes at diagnosis does not adversely affect prognosis 30 31 32 33 . Factors associated with a poor prognosis are skull base involvement 33 34 35 , extent of the primary tumor 31 32 and cranial nerve involvement 33 34 .

1. What is the optimum radiotherapy dose?

2. Would exclusion of interferon from the treatment produce similar results?

3. The relationship between late effects and dose of radiotherapy should be investigated, as well as the exact nature and incidence of late effects.