Nasopharyngeal carcinoma

doi:10.1016/S0140-6736(15)00055-0

The Lancet

Volume 387, Issue 10022, 5–11 March 2016, Pages 1012-1024

https://doi.org/10.1016/S0140-6736(15)00055-0 Get rights and content

Summary

Epidemiological trends during the past decade suggest that although incidence of nasopharyngeal carcinoma is gradually declining, even in endemic regions, mortality from the disease has fallen substantially. This finding is probably a result of a combination of lifestyle modification, population screening coupled with better imaging, advances in radiotherapy, and effective systemic agents. In particular, intensity-modulated radiotherapy has driven the improvement in tumour control and reduction in toxic effects in survivors. Clinical use of Epstein-Barr virus (EBV) as a surrogate biomarker in nasopharyngeal carcinoma continues to increase, with quantitative assessment of circulating EBV DNA used for population screening, prognostication, and disease surveillance. Randomised trials are investigating the role of EBV DNA in stratification of patients for treatment intensification and deintensification. Among the exciting developments in nasopharyngeal carcinoma, vascular endothelial growth factor inhibition and novel immunotherapies targeted at immune checkpoint and EBV-specific tumour antigens offer promising alternatives to patients with metastatic disease.

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.

Section snippets

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

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

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Characteristics of Tongue Pressure Measured by Novel Multisite Flexible Sensors in Nasopharyngeal Carcinoma Patients With Dysphagia
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SeminarNasopharyngeal carcinoma

Summary

Introduction

Section snippets

Pathology and risk factors

Population screening in endemic areas

Symptoms and diagnosis

Staging and prognosis

Imaging studies

Radiotherapy in the management of nasopharyngeal carcinoma

Chemotherapy in non-metastatic disease

Disease surveillance and toxic effects

Management of residual or recurrent disease

Management of distant metastasis

Conclusions and future directions

Search strategy and selection criteria

Lancet

Semin Cancer Biol

Oral Oncol

Int J Radiat Oncol Biol Phys

Semin Cancer Biol

Semin Cancer Biol

Am J Hum Genet

J Transl Med

Int J Radiat Oncol Biol Phys

Eur J Radiol

Radiother Oncol

Int J Radiat Oncol Biol Phys

Radiother Oncol

Radiother Oncol

Int J Radiat Oncol Biol Phys

Radiother Oncol

Radiother Oncol

Int J Radiat Oncol Biol Phys

Ann Oncol

Eur J Cancer

Radiother Oncol

Ann Oncol

Lancet Oncol

Lancet Oncol

Radiother Oncol

Ann Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Oral Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Ann Oncol

Int J Radiat Oncol Biol Phys

Radiother Oncol

Radiother Oncol

GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11

Is nasopharyngeal cancer really a “Cantonese cancer”?

Chin J Cancer