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Cancer, Nasopharyngeal Carcinoma (NPC)

Authors

Abdul Basit Shah1; Hassam Zulfiqar2; Shivaraj Nagalli3.

Affiliations
1 University of Health Sciences
2
Rawalpindi Medical University
3 Yuma Regional Medical Center

Last Update: January 28, 2020.

Introduction
Nasopharyngeal carcinoma (NPC), previously known as lymphoepithelioma, is a malignancy arising from the
epithelium of the nasopharynx. Endemic to China, the malignancy shows a variable rate of occurrence ranging from
high incidence in the Southern part of China to a low rate in the White population and Northern China with the
incidence ranging from 15 to 50 per 100000. A complex interplay of genetic susceptibility and Epstein Barr virus
(EBV) infection is responsible for the disease.[1]

Etiology
An interplay of environmental factors, genetic structure, and EBV infection is involved in the etiology of the disease.
Environmental factors, including smoking in the western population and nitrosamines containing food agents, have
been considered to have an involvement. Secondly, the genetic structure of the demographics involved also plays a
vital role, as explained by the overwhelming incidence in the Chinese population. Lastly, EBV infection, coupled with
genetic susceptibility, has shown a substantial relevance to the disease.[2][3]

Epidemiology
Nasopharyngeal carcinoma (NPC) is highly endemic to Southern China, Malay and Indonesian population along with
people from Southeast Asia. The rate varies from a minuscule value of less than 1 per 100000 individuals in non-
endemic areas to a high value of 25 to 30 and 15 to 20 males and females per 100000 individuals in endemic areas,
respectively.[4]

Histopathology
Histopathological evaluation can elucidate in which category does the tumor fall. On histopathological grounds, NPC
can fall into three main sub-groups as per WHO classification[5]:

1. Keratinizing type (20% to 25%)

2. Non-keratinizing differentiated type (10% to 15%)

3. Non-keratinizing undifferentiated (60% to 65%)

History and Physical

Patients can have variable presentations depending on the area of involvement of the disease.

Nasal symptoms: A subset of patients present with nasal symptoms ranging from nasal obstruction, blood-

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tinged nasal discharge, and post-nasal drip to denasalization of voice and cacosmia. Symptomatology is
proportionate to the size of growth and the extent of local involvement. Around 80% of the individuals suffering
from the disease present with nasal symptoms

Otological symptoms: Patients present with symptoms secondary to eustachian tube blockage, i.e., conductive
hearing loss, effusions and fullness, and tinnitus. Half of the patients with NPC have some form of otological
complaint during the disease caused because of the growing mass obstructing the outflow of the eustachian tube.

Neurological symptoms: Intracranial extension is prevalent among 8% to 12% of the demographic — various
forms of cranial nerve involvement present with the associated symptom. The most commonly involved nerve is
the abducens nerve.[6]

Nodal involvement: One of the most common presenting features would be an enlarged neck node. Lymph
nodes of the apex of the posterior triangle and the upper jugular are most commonly involved initially.
Supraclavicular nodes are the last to be involved and are a sign of advanced disease.[7]

Distant metastasis and paraneoplastic syndrome: Symptoms associated with distant spread rarely present to the
primary caregiver. The most significant spread includes the liver and lungs. It is sometimes difficult to assess the
primary site of malignancy when metastatic pulmonary lesions occur. PET scan aids in the differentiation of the two.
Secondly, a handful of cases present with symptoms of dermatomyositis. The progression of the disease might initiate
with the malignant lesion or can present after the initial diagnosis of NPC.[8]

Evaluation
Lab Investigations

Baseline investigations which include complete blood count, renal and liver function tests can be sent for initial
scrutiny. An abnormality would be detected in cases where a hepatic extension is suspected along with a
deterioration in renal function as the tumor divides at a rapid pace.

Epstein Barr virus invariably has involvement in the pathogenesis of the disease process. To establish an
association, serum IgA levels are necessary. These carry both diagnostic and prognostic significance for the
disease process.[8]

Imaging Studies

CT scan: A local tumor is visible, extending from the roof of the pharynx. CT scan is the modality of choice as
far as bone invasion, and intracranial extension is also present. However, radiation exposure and its limited
value in terms of soft tissue extension and nodal metastasis make MRI the preferred modality.

MRI scan: MRI is the superior modality for assessing the tumor extension into the musculature and the nodal
metastasis. The tumor bulk, along with local invasion, can be easily visualized and does not pose any threat of
radiation.

PET scan: It is the modality of choice for assessing remission and for investigating recurrence. PET-CT scan can
augment the extent of distant metastasis as it is a whole-body scan. However, MRI can provide a higher level of
local delineation, making it still the investigation of choice for local spread.[9]

Endoscopic Evaluation and Histopathological Analysis

The tumor is visible via nasopharyngoscopy, and the local extension along with tumor size is assessable, and
biopsy possible. However, the assessment becomes hindered if the mass is too large for accessing the passage.

Treatment / Management

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The mainstay of treatment for NPC is radiotherapy in locoregional lesions as the non-keratinizing variety is highly
radiosensitive. Surgical intervention is limited to salvage procedures in recurrent diseases, whereas chemotherapy is
preferred concomitantly with radiation in advance stages.

Radiotherapy

Radiation is the management of choice for the loco-regional lesion. Radiotherapy is effective in all cases except those
for distant metastasis hence from stage I to stage IVB. NPC shows a tendency for quick spread regionally, especially
as the nasopharynx is a small cavity so spread to paranasopharyngeal spaces, musculature, and nodes common. Also,
progressively involving the contralateral side is not a rare occurrence. Consequently, a dose of approximately 65 Gy
for primary tumor with 50 to 55 Gy is also necessary for nodal negative necks.

A recent innovation in the delivery system employed for radiation is intensity modulation or intensity-modulated
radiotherapy (IMRT). The system comes equipped with a CT taking slices of the area involved. The physician
specifies the targeted area of the beam and modulates the intensity of the beam employed.[10]

Brachytherapy is another innovative technique for targeted radiotherapy. The technique used is the implantation of
gold grains or iridium implants, jacketed for localized radiotherapy, via a split incision of the soft palate. The
technique is useful for localized tumor bulk that has not shown any intracranial extension. The technique spares any
local vital organ damage.

Radiotherapy is also employed when treatment failure or recurrence occurs. It has been proven useful in both local
recurrence and nodal failures. In such cases, brachytherapy is considered keeping in mind the friability of the local
tissue, the general condition of the patient, and the impact on vital organs of the region.[3][9]

Chemotherapy

NPC is highly sensitive to radiation and chemotherapy. In locally advanced regional disease, concomitant
chemoradiotherapy is the mainstay of management. The disease responds better with induction, and concurrent
therapy is significant in shrinking the tumor bulk. The most frequently used agent as the initial line of
chemotherapeutic intervention is Cisplatin. The standard of care is a dose of 100 mg every third week.

Chemotherapy is also the option of choice when distant metastasis is involved. NPC with distant poly-metastasis is
offered palliative chemotherapy. The agents of choice are cisplatin and 5-fluorouracil. With recent advances, several
chemotherapeutic agents are available for the continuation of therapy. However, the median survival rate is not more
than a year.[3][9]

Surgical Intervention

Surgical intervention is employed only as a salvage option. The nasopharynx is a small and deep area that is hard to
access, thus making the surgical approach to it sometimes difficult and inappropriate. However, when encoutnering
locally recurring disease, patients should be given the option of surgical intervention. Surgery is also one of the key
modes of management for distant oligo-metastasis in conjunction with radiotherapy and radio ablation.[11][12]

Nasopharyngectomies are carried out by several approaches, and the approach decided should be tailored in
accordance with the expertise of the surgeon and the general condition of the patient. The following are some of the
popular approaches to the cavity.

Inferior approach- via transpalatal incision

Lateral approach- via the lateral skull base

Inferolateral approach

Midfacial degloving

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Endoscopic approach

Radical neck dissections often accompany the procedures mentioned above, where extensive neck involvement is
present. Also, in recurring disease, especially nodal recurrence, radical neck dissection is done as a component of
salvage therapy.

Differential Diagnosis
Differential diagnosis of NPC depends on regional lesions involving the nasopharynx and mimicking the
symptomatology. Categorization is possible regarding the nature of the lesion as follows:

Benign conditions

Nasopharyngeal polyposis

Angiofibromas

Malignant lesions

Lymphomas,

Salivary gland tumors

Sinonasal carcinomas

Malignant mucosal melanomas

Staging
The nuances in imaging techniques and the improved outcomes associated with optimum therapy have caused the
American Joint Committee on Cancer (AJCC) to reevaluate the staging process. As per the recent guidelines, the TNM
staging has been explained as per the following criteria[13]:

Primary Tumor (T):

Tx: Inability to assess the tumor.

T1: Nasopharyngeal involvement sparing the parapharyngeal spaces

T2: Extension into the parapharyngeal spaces and may or may not extend into regional muscles(Pterygoids and
prevertebral)

T3: Invasion of skull and sinuses

T4: Intracranial extension with the involvement of Cranial nerves, pterygoids, and orbit.

Nodal metastasis (N):

NX: Inability to assess nodal involvement

N0: No involvement

N1: A unilateral spread not exceeding 6 cm in maximum dimensions confined above supraclavicular fossa

N2: A bilateral spread not exceeding 6 cm in maximum dimensions confined above supraclavicular fossa

N3: Metastasis

N3a: involvement greater than 6 cm

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N3b: supraclavicular fossa involvement

Distant Metastasis (M):

MX: Inability to assess metastasis

M0: No distant involvement

M1: Distant Involvement.

Stage grouping:

Stage 0: T1s-N0-M0

Stage I: T1-N0-M0

Stage II: T1-N1-M0 and T2-N0-M0

Stage III: T1, T2-N2-M0 and T3-N0, N1, N2-M0

Stage IVA: T4-N0, N1, N2-M0

Stage IVB: Any T-N3-M0

Stage IVC: Any T-Any N-M1

Prognosis
The overall prognosis and the 5-year survival rate has improved since the advent of nuances in the radiotherapy
techniques. This change shows a drastically decreased the mortality and morbidity associated with illness from a
reported 5-year survival of 25% to 40% to approximately 70% in the past decade.[14]

Complications
Lesions can have local complications, including obstruction of Eustachian tubes causing otitis media with effusion
(OME), persistent nasal obstruction, and obstruction of the oropharyngeal airway. Mass effect causing blockage of
oropharynx impedes swallowing, and if it remains unchecked, its progression may lead to blockage of the airway.
Intracranial extension and involvement of cranial nerves are debilitating and can have a lifelong disability even after
management.[15]

Deterrence and Patient Education

Patients endemic to prevalent areas should be more vigilant regarding the symptoms of the disease. Moreover, the
demographics of the western population having environmental factors (smoking, etc.) associated with NPC should
also receive education regarding their hazardous effects. Also, the subset of people having genetic susceptibility along
with recurrent EBV infection should have a higher index of suspicion for the disease.

Pearls and Other Issues

NPC is a malignancy having a variable incidence depending on the region.

Endoscopic biopsy should be the first and foremost step for the evaluation of the lesion.

NPC has a high index of susceptibility to radiotherapy; hence should be considered in almost all forms of the
disease at the initial presentation. Coupling the effectiveness of this mode of management with difficulty
associated with the surgical approach to the region makes radiotherapy the therapy of choice.

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In advance cases, chemotherapy is given concomitantly to produce optimum results. The drug of choice is
cisplatin initially, given concomitantly with radiotherapy.

Enhancing Healthcare Team Outcomes

Endemic areas have made strides in this regard as they have increased their index of suspicion towards such
malignancies at the primary care physician level. NPC requires the efforts of an interprofessional team.

After diagnosis, a radiotherapist and oncologist should educate the patient regarding the favorable outcome associated
with strict adherence to the program. Otolaryngology and otolaryngology nurses provide care and education to these
patients. Board-certified oncologic pharmacists review prescriptions and check for drug-drug interactions. Oncology
specialty nursing staff can administer chemotherapy, assist in post-procedural care and monitoring, and report any
concerns to the treating clinicians. Prolonged therapy has complications of itself that are manageable in follow-up
clinics. Also, patients having the psychological burden, benefit from structured support groups and psychologist
sessions. [Level 5]

Questions
To access free multiple choice questions on this topic, click here.

References
1. Du T, Xiao J, Qiu Z, Wu K. The effectiveness of intensity-modulated radiation therapy versus 2D-RT for the
treatment of nasopharyngeal carcinoma: A systematic review and meta-analysis. PLoS ONE.
2019;14(7):e0219611. [PMC free article: PMC6619803] [PubMed: 31291379]
2. Sun L, Wang Y, Shi J, Zhu W, Wang X. Association of Plasma Epstein-Barr Virus LMP1 and EBER1 with
Circulating Tumor Cells and the Metastasis of Nasopharyngeal Carcinoma. Pathol. Oncol. Res. 2019 Dec 12;
[PubMed: 31832991]
3. Adoga AA, Kokong DD, Ma'an ND, Silas OA, Dauda AM, Yaro JP, Mugu JG, Mgbachi CJ, Yabak CJ. The
epidemiology, treatment, and determinants of outcome of primary head and neck cancers at the Jos University
Teaching Hospital. South Asian J Cancer. 2018 Jul-Sep;7(3):183-187. [PMC free article: PMC6069340] [PubMed:
30112335]
4. Cao SM, Simons MJ, Qian CN. The prevalence and prevention of nasopharyngeal carcinoma in China. Chin J
Cancer. 2011 Feb;30(2):114-9. [PMC free article: PMC4013340] [PubMed: 21272443]
5. Peng G, Wang T, Yang KY, Zhang S, Zhang T, Li Q, Han J, Wu G. A prospective, randomized study comparing
outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the
treatment of nasopharyngeal carcinoma. Radiother Oncol. 2012 Sep;104(3):286-93. [PubMed: 22995588]
6. Mo HY, Sun R, Sun J, Zhang Q, Huang WJ, Li YX, Yang J, Mai HQ. Prognostic value of pretreatment and
recovery duration of cranial nerve palsy in nasopharyngeal carcinoma. Radiat Oncol. 2012 Sep 07;7:149. [PMC
free article: PMC3533812] [PubMed: 22958729]
7. Batsakis JG, Solomon AR, Rice DH. The pathology of head and neck tumors: carcinoma of the nasopharynx, Part
11. Head Neck Surg. 1981 Jul-Aug;3(6):511-24. [PubMed: 7251374]
8. Teoh JW, Yunus RM, Hassan F, Ghazali N, Abidin ZA. Nasopharyngeal carcinoma in dermatomyositis patients: A
10-year retrospective review in Hospital Selayang, Malaysia. Rep Pract Oncol Radiother. 2014 Sep;19(5):332-6.
[PMC free article: PMC4150095] [PubMed: 25184058]
9. Blanchard P, Nguyen F, Moya-Plana A, Pignon JP, Even C, Bidault F, Temam S, Ruffier A, Tao Y. [New
developments in the management of nasopharyngeal carcinoma]. Cancer Radiother. 2018 Oct;22(6-7):492-495.
[PubMed: 30087054]
10. Lee N, Harris J, Garden AS, Straube W, Glisson B, Xia P, Bosch W, Morrison WH, Quivey J, Thorstad W, Jones
C, Ang KK. Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma:
radiation therapy oncology group phase II trial 0225. J. Clin. Oncol. 2009 Aug 01;27(22):3684-90. [PMC free

6 of 11 28/05/2020, 8:01
Cancer, Nasopharyngeal Carcinoma (NPC) - StatPearls - NCBI Bookshelf https://www.ncbi.nlm.nih.gov/books/NBK554588/?report=printable

article: PMC2720082] [PubMed: 19564532]

11. Liu J, Yu H, Sun X, Wang D, Gu Y, Liu Q, Wang H, Han W, Fry A. Salvage endoscopic nasopharyngectomy for
local recurrent or residual nasopharyngeal carcinoma: a 10-year experience. Int. J. Clin. Oncol. 2017
Oct;22(5):834-842. [PubMed: 28601934]
12. Hay A, Simo R, Hall G, Tharavai S, Oakley R, Fry A, Cascarini L, Lei M, Guerro-Urbano T, Jeannon JP.
Outcomes of salvage surgery for the oropharynx and larynx: a contemporary experience in a UK Cancer Centre.
Eur Arch Otorhinolaryngol. 2019 Apr;276(4):1153-1159. [PubMed: 30666441]
13. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR,
Winchester DP. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a
population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin. 2017 Mar;67(2):93-99.
[PubMed: 28094848]
14. Li J, Chen S, Peng S, Liu Y, Xing S, He X, Chen H. Prognostic nomogram for patients with Nasopharyngeal
Carcinoma incorporating hematological biomarkers and clinical characteristics. Int. J. Biol. Sci.
2018;14(5):549-556. [PMC free article: PMC5968847] [PubMed: 29805306]
15. Ho AC, Chan JY, Ng RW, Ho WK, Wei WI. The role of myringotomy and ventilation tube insertion in maxillary
swing approach nasopharyngectomy: review of our 10-year experience. Laryngoscope. 2013 Feb;123(2):376-80.
[PubMed: 22951935]

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Figures

PET- Scan of a patient showing A hyper-metabolic soft tissue lesion measuring 13 x 10 mm is seen in right
nasopharynx. Contributed by Abdul Basit

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A CT image of a patient with a Left sided nasopharyngeal mass involving the posterior pharyngeal wall and
showing minor opacification of the maxillary antrum bilateral. Contributed by Abdul Basit.

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Staging Table 01. Contributed by Abdul Basit Shah, MBBS

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Staging Table 02. Contributed by Abdul Basit Shah, MBBS

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