We searched the PubMed and MEDLINE databases for articles published in English from Jan 1, 2000, to Dec 31, 2014, with the keywords “nasopharyngeal carcinoma”, “epidemiology”, “pathology”, “genetics”, “Epstein-Barr virus”, “human papilloma virus”, “staging”, “imaging”, “functional magnetic resonance imaging”, “positron emission tomography”, “radiotherapy”, “intensity-modulated radiotherapy”, “adaptive radiotherapy”, “chemotherapy”, “salvage therapy”, “immunotherapy”, “clinical trials”, and
SeminarNasopharyngeal carcinoma
Introduction
Nasopharyngeal carcinoma is a cancer arising from the nasopharynx epithelium. Within the boundaries of the nasopharynx, the tumour epicentre is frequently seen at the fossa of Rosenmüller, from where the tumour invades adjacent anatomical spaces or organs. Despite being of a similar cell or tissue lineage, distinct differences exist between nasopharyngeal carcinoma and other epithelial tumours in the head and neck region.
Compared with other cancer types, nasopharyngeal carcinoma is uncommon, albeit with a very unique pattern of geographical distribution. Worldwide, 86 500 cases of nasopharyngeal carcinoma were reported in 2012, accounting for only 0·6% of all cancers diagnosed in that year. 71% of new cases were in east and southeast parts of Asia, with south-central Asia, and north and east Africa accounting for the remainder (appendix).1
Besides geographical variation, some ethnic groups also seem to have a predisposition for nasopharyngeal carcinoma—eg, the Bidayuh in Borneo, Nagas in northern India, and Inuits in the Artic, in whom age-standardised incidence is reportedly higher than 16 per 100 000 person-years in men.2 In terms of demographic trends, men are two to three times more likely to develop the disease than are women, and peak age of disease occurrence is between 50 and 60 years. In view of the heterogeneous epidemiological patterns, it is possible that other factors, not limited to genetic susceptibility, are implicated in the pathogenesis of nasopharyngeal carcinoma.
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Pathology and risk factors
Morphologically, an abundance of lymphoid cells is often seen intermixed with transformed epithelial cells, but nasopharyngeal carcinoma is widely regarded to be squamous in origin. Depending on the degree of differentiation, nasopharyngeal carcinoma is categorised into three pathological subtypes on the basis of WHO criteria. Differentiated tumours with surface keratin are defined as type I, whereas types II and III refer to non-keratinising differentiated and undifferentiated tumours,
Population screening in endemic areas
In view of the prevalence of nasopharyngeal carcinoma in southern China, population screening presents an attractive strategy for early diagnosis and, consequently, better outcomes. Immunoserology (IgA antibodies against EBV capsid antigen [VCA-IgA], early antigen [EA-IgA], EBV nuclear antigen 1 [EBNA1-IgA], and EBV-specific DNase antibodies) and EBV DNA-based screening methods have been studied. From the early studies consisting of case-control and prospective testing, immunoseropositivity is
Symptoms and diagnosis
Clinical presentation of nasopharyngeal carcinoma is correlated with the extent of primary and nodal disease. Possible routes of primary tumour invasion are anterior spread into the nasal cavity, pterygoid fossa, and maxillary sinuses; lateral involvement beyond the pharyngobasilar fascia into the parapharyngeal and infratemporal spaces; and base of skull, clivus, and intracranial structures when the disease extends posteriorly and superiorly. Hence, depending on the anatomical structures
Staging and prognosis
Nasopharyngeal carcinoma is classified by the joint Union for International Cancer Control TNM Classification of Malignant Tumours and the American Joint Committee on Cancer staging system. This classification system was updated in 2009 and introduced several modifications to the staging of primary and nodal disease for the seventh edition (appendix).34
Besides tumour burden as reflected by the TNM stage classification, other clinical and molecular prognostic variables have also been proposed. A
Imaging studies
Optimum imaging is crucial for staging and radiotherapy planning of nasopharyngeal carcinoma. MRI provides better resolution than CT in terms of assessing parapharyngeal spaces, marrow infiltration of the skull base, intracranial disease, and deep cervical nodes. The advent of functional MRI adds a biological dimension. Parameters of cellularity (diffusion) and perfusion have been correlated to clinical stage of nasopharyngeal carcinoma.45 Likewise, 18F-fluorodeoxyglucose (18F-FDG)-PET provides
Radiotherapy in the management of nasopharyngeal carcinoma
Radiotherapy is the primary and only curative treatment for nasopharyngeal carcinoma. In centres where modern radiation technology is available, intensity-modulated radiotherapy (IMRT) is the preferred method. Briefly, this technique caters for delivery of tumoricidal doses to gross tumour and subclinical disease, while minimising doses to adjacent normal tissues. Such a technology is particularly advantageous in nasopharyngeal carcinoma, in view of the late toxic effects reported in patients
Chemotherapy in non-metastatic disease
The strategy of combining chemotherapy with radiotherapy is another pivotal advancement in the treatment of locally advanced nasopharyngeal carcinoma. Since the publication of the seminal INT-0099 trial, several trials have substantiated the benefits in disease control and survival reported with chemoradiotherapy, henceforth establishing this treatment as the standard of care in this subgroup (table 2).63, 64, 65, 66, 67, 68, 69, 70, 71 Combination regimens varied between studies, but for the
Disease surveillance and toxic effects
Initial post-treatment assessment entails monitoring of acute effects and tumour response. Common acute radiotherapy-related effects include mucositis, dysphagia, dermatitis, and xerostomia. Clinical symptoms typically improve within weeks after treatment cessation, but in instances of grade 3 or 4 reactions, these can persist, leading to consequential late effects. Chemoradiotherapy is invariably associated with higher incidences of haematological and non-haematological acute toxic effects
Management of residual or recurrent disease
Local recurrences in the nasopharynx can be salvaged with either surgery or radiotherapy. In principle, small rT1–2 tumours are amenable to surgery, brachytherapy, or stereotactic radiosurgery, whereas rT3–4 lesions are best treated with external beam, preferably IMRT. Generally, tumours that recur within a year are deemed radioresistant, and surgery is recommended if resection with adequate margins is feasible. In all cases, rightful caution has to be accorded to repeat irradiation given the
Management of distant metastasis
Treatment of patients with metastatic nasopharyngeal carcinoma (stage IVC) has evolved, with a shift towards personalised treatment for this group of patients.115 Foremost, it is acknowledged that outcomes of patients with metastatic nasopharyngeal carcinoma are heterogeneous and long-term survivorship is possible. Stratification for these individuals can be done on the basis of clinical characteristics such as lung alone metastasis, oligometastasis, metachronous relapse, and the absence of
Conclusions and future directions
Epidemiological studies undertaken over the past few decades continue to reveal a gradual but progressive decline in the incidence of nasopharyngeal carcinoma, and a substantial reduction in mortality.144, 145 These trends are probably a result of enhanced understanding in the pathogenesis and risk factors of the disease, and the biological mechanisms underlying the prognostic risk stratification. Advances in treatment on all fronts (radiotherapy and chemotherapy) also had a huge effect on the
Search strategy and selection criteria
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