ReviewNasopharyngeal carcinomas: an update
Introduction
Nasopharyngeal Carcinoma (NPC) differs from other head and neck carcinomas, in terms of its epidemiology, pathology, clinical features, treatment and outcome. Many histological entities exist from Squamous Cell Carcinoma (SCC) to the more frequent Undifferentiated Carcinoma of the Nasopharyngeal Type (UCNT), and these entities share endemic areas throughout the world. UCNT is associated with the Epstein–Barr Virus (EBV). This is of interest not only for epidemiological reasons or diagnosis, but also for the monitoring of patients, prognosis of patients and therapeutic strategies for the patients 1, 2, 3. NPC is also characterised by its relatively high sensitivity to radiation, although local recurrences and metastases are common events. In patients with locally advanced disease, chemotherapy in combination with radiotherapy has a proven efficiency in terms of the long-term disease-free survival rates [4] that have recently been reported in randomised trials 5, 6. This article reviews the current knowledge with regard to the epidemiology, the biology and the treatment experience and outcome of patients with NPC.
Section snippets
Epidemiology
NPC are rare in most countries, especially in Europe and North America (incidence below 1/100 000). However, it has a high incidence in several areas in Southern China, especially in the Cantonese region around Guangzhou, where the incidence is approximately 30–80/100 000 people per year [7]. Other areas of high incidence include Taiwan, Vietnam and the Philippines. In these areas, it is likely that diet plays a carcinogenic role as the population's diet consists of salt-cured fish and meat,
Anatomy
The nasopharyngeal region is situated anteriorly in continuity to the nasal cavity through the posterior choanae, above the basisphenoid and the basiocciput that constitute the roof of the nasopharynx that comes down behind by the posterior wall, constituted itself by the first two cervical vertebrae. The eustachian tube ostium situated in the lateral walls of the nasopharynx and the lateral pharyngeal recess or fossa of Rosenmuller remain the most common site for the initial development of
Pathology
Pathology has an important impact on outcome and the WHO has classified NPC into three histological types: keratinising squamous cell carcinoma (type 1), non-keratinising carcinoma (type 2) and the most common tumour, the undifferentiated carcinoma UCNT (type 3) [50].
Other histological forms include lymphoma or plasmocytoma.
With regard to the histogenesis, despite numerous attempts, there has been no real characterisation of the premalignant lesions of the nasopharyngeal epithelium. In 1995,
Diagnosis
Most of time, NPC derives in the fossa of Rosenmuller and arises as a mass in the neck with symptoms such as hearing problems, serous otitis, tinnitus, nasal obstruction, anosmia, bleeding, difficulty in swallowing due to cranial nerve XII involvement or dysphonia if the nerve X is invaded by the tumour, even eye symptoms with diplopia (VI nerve invasion) and pain [54]. However, none of these symptoms is specific for NPC and sometimes NPC develops at the submucosal level and spreads outside of
Staging
There are several clinical staging systems used in this disease, depending on the country. For instance, the most common classification used in Asia is derived from the Ho clinical study [70] whereas the International Union Against Cancer/American Joint Committee on Cancer (UICC-AJCC) system [71] remains the most frequently used system in countries other than Asia (Table 1). Anyway, there seems to be no difference between these staging systems, except in one study where the Ho staging system
Pathology
The pathological type is a prognostic factor. In Western countries, squamous cell carcinoma (WHO type 1) has a worse outcome in terms of local control and overall survival than WHO types 2–3 55, 78. However, a high proportion of dendritic cells and macrophages in lymphoid infiltrations has been shown to be associated with a better prognosis [80].
Treatment
NPC remains a relatively radiosensitive tumour and thus radiation therapy remains the standard treatment for almost all NPC patients. By contrast, surgery is generally not feasible due to potentially inadequate margins of resection. Despite improvements in treatment modalities, regional recurrences are not uncommon and the pattern of failure for patients with NPC differs from that of other cancer sites of the head and neck, with a higher distant failure rate [75]. Thus, chemotherapy is
Chemotherapy
Although radiation therapy remains the mainstay treatment, some pathological types of NPC (types 2 and 3) have been shown to be chemosensitive in all stages of the disease 120, 121, 122. Moreover, some cases of NPC can be locally controlled by chemotherapy alone [120]. Although complete response rates (CRs) are generally higher in UCNT patients with a similar or greater stage tumour than in other head and neck SCC patients, the local recurrence rates and rates of distant metastases remain
Treatment of recurrent disease
The main cause of death in NPC patients remains distant failure. Metastases can occur in different sites, with a preferential skeletal spread. A relationship was even demonstrated between local recurrences and metastasis [139]. For patients with local recurrence, a second course radiotherapy may be administered with caution. Many therapeutic techniques have been evaluated, e.g. external re-irradiation, brachytherapy, surgery and chemotherapy or combined modalities. A second course of
Conclusions
NPC are a very distinct type of head and neck cancer, in terms of their epidemiology, clinical presentation, outcome and treatment strategy. Some prognostic factors, such as locoregional extension, are well known. NPC are relatively radiosensitive and chemosensitive when compared with other head and neck cancers. Treatment strategies are multidisciplinary, combining radiotherapy with chemotherapy. The most important issue in NPC advanced patients is the high rate of treatment failure, with a
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