ORIGINAL ARTICLE

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Nasopharyngeal carcinoma: differences in presentation between different ethnicities in the New Zealand setting
ans_5132 254..257

Ilia Ianovski,* Mark Izzard,* Randall P. Morton and Lindsay D. Plank

*ORL Department, Auckland City Hospital ORL Department, Counties Manukau DHB Department of Surgery, School of Medicine, University of Auckland, Auckland, New Zealand

Key words Nasopharyngeal carcinoma, TNM stage, ethnicity, New Zealand. Abbreviations AJCC, American Joint Committee on Cancer; CT, computed tomography; MPI, Maori and Pacic Island; MRI, magnetic resonance imaging; NPC, nasopharyngeal carcinoma. Correspondence Dr Ilia Ianovski, 2-9 Bowling Ave, Epsom, Auckland, New Zealand. Email: blindrevelations@gmail.com I. Ianovski MBChB, BHB; M. Izzard MBBS, FRACS; R. P. Morton MBBS, FRACS, MSc (Med); L. D. Plank D.Phil. The corresponding author is not a recipient of a research scholarship. The following paper is not based on a previous communication to a society or meeting. Accepted for publication 17 August 2008. doi: 10.1111/j.1445-2197.2009.05132.x

Abstract
Introduction: There is an elevated incidence of nasopharyngeal carcinoma (NPC) in the Maori and Pacic Island (MPI) population as well as the Asian population in New Zealand; however, no studies have been conducted to evaluate how the two populations differ in their clinical presentation according to the TNM stage. Methods: A retrospective review was conducted of all patients presenting to the Auckland City Hospital ENT department with a newly diagnosed NPC between the years 1995 and 2007 inclusive. The patients radiological and biopsy results were reviewed, and each patient was staged according to the TNM stage at presentation as per the revised 2002 American Joint Committee on Cancer staging criteria. The Fishers exact test was used to compare the differences between ethnicities in the T and N stages of the disease at presentation; the CochranArmitage Trend test was used to look for statistically signicant trends. Results: There was a statistically signicant difference in T stage at presentation between MPIs and Asians (P < 0.0001), with a positive, statistically signicant (P < 0.0001) trend indicating that MPIs present with greater T stage. A statistically signicant difference in the N stage at diagnosis between MPIs and Asians, independent of the T stage, was found at stages T2 (P = 0.046) and T4 (P = 0.0083), with a statistically signicant trend (T2 P = 0.009; T4 P = 0.026). Conclusions: These results show that MPIs have a more advanced local NPC disease than Asians at presentation, and that for specic T stages, the nodal disease is also more advanced than that found in Asians.

Introduction
Nasopharyngeal carcinoma (NPC) is an aggressive tumour of the head and neck, with a variable incidence rate around the world. In the Western world (United States and Europe), the annual incidence is estimated at 1/100 000,1 but in Southern China, parts of South East Asia, the Mediterranean basin and Alaska, the annual incidence is 1030/100 000.2 These epidemiological differences have been attributed to three aetiological factors: genetic susceptibility, exposure to dietary or environmental carcinogens and latent Epstein-Barr Virus (EBV) infection.3 In New Zealand, the main ethnic groups are Europeans (67.6%), Maori (14.6%), Pacic Islanders (6.9%) and Asians (9.2%).4 The New Zealand Europeans have the same incidence of NPC as do their counterparts in Europe and North America. However, Maori and

Pacic Islanders (MPIs) have a much higher incidence of NPC, estimated at 10/100 000.5,6 There is evidence that Pacic Islanders inhabiting the South Pacic region are descended from the Asian population that once inhabited Southern China.6 Thus, the higher incidence of NPC in MPIs may be attributed to a shared ancestral genetic susceptibility. The Asian population of New Zealand is mostly made up of immigrants from China (Including Hong Kong and Taiwan).7 The reported incidence of NPC in Hong Kong and the Guangdong province of China (geographically adjacent regions), where it is most prevalent, is 2030/100 000 for men and 1520/100 000 for women,8 and the incidence of NPC remains the same in Chinese immigrants to United States, UK and Australia but decreases in the next generation that is born in the country of immigration.8,9 The Asian population in New Zealand is mostly made up of
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rst-generation immigrants, and has been shown to have an incidence of NPC that matches the pattern of occurrence in their place of origin closely.5 We have observed that MPI patients and Asian patients with NPC seemed to vary in disease extent at the time of presentation, and that the MPIs seemed to have more bilateral neck nodal disease than the Asian group. The purpose of this study was to examine differences in presentation between MPIs and Asians with NPC, in terms of the TNM stage of their disease, to see whether the disease has changed in the MPI group compared with its ancestral parent group.

Results
A total of 161 patients were seen with the diagnosis of NPC in the time frame of the study. Thirty-three were excluded from the analysis as they were either diagnosed prior to 1995 or were initially treated in a different centre. This left 128 newly diagnosed NPCs, 81 (63%) men and 47 (37%) women (M:F = 1.7:1). Throughout the 12 years of the study, the rate of presentation was between 8 to 12 new patients per annum. Of the 128 study participants, 58 (45%) were of Asian ethnicity, 14 (11%) Maori, 41 (32%) Pacic Islanders, 14 (11%) New Zealand European/Europeans and one (0.01%) Indian. Combined, MPI participants comprised 55 cases (43% of the study population). Most (107) patients had a CT scan only (84%), 15 had a CT and an MRI (12%) and six had an MRI only (4%), as part of their initial diagnostic investigations. The distribution of the T stage at presentation is shown on Figure 1. Four patients had distant metastasis at presentation; two were Maori with bone metastasis one with T2aN3bM1 and one with T4N0M1, and two were Europeans with liver metastasis one with T3N3bM1 and one with T4N0M1. None of the Asian NPC patients had any evidence of distant metastasis at presentation. There was a statistically signicant difference between MPIs and Asians for T stage at diagnosis (P < 0.0001, Fishers exact test), indicating an independent inuence of ethnicity on the primary tumour volume at presentation. There was a positive, statistically signicant trend (P < 0.0001, CochranArmitage Trend test) indicating that MPIs present with a greater T stage at initial diagnosis of NPC, when compared with the Asian population. The comparison of T stage at initial diagnosis between Maori and Asians and Pacic Islanders and Asians both showed a statistically signicant difference between the two groups (P = 0.018 and P < 0.0001, respectively, shers Exact test). The trend tests for both of the above were also positive, with P = 0.028 for Maori and Asians, and P < 0.0001 for PIs and Asians. This indicates that when separated into MPI independently, and compared with the Asian population, ethnicity remains associated with T stage at the time of diagnosis, with a trend for both MPI to present with greater T levels compared with the Asians. The raw numbers suggested that the MPIs present with bilateral disease more often than Asians at each T stage of the cancer (Table 1). While the differences were not signicant for T1, T3 and T4, the difference was statistically signicant for T2 lesions (P = 0.017, Fishers exact test). When MPIs and Asians were also analysed in respect of N stage, after controlling for T stage, the MPIs tended to have higher N stages (Table 2). For the purpose of statistical analysis, the N3a and N3b nodal disease was analysed together as N3. This was done as a number of patients presented with both N3a and N3b nodal disease. There was a statistically signicant difference between MPIs and Asians at T2 and T4 (P = 0.046 and P = 0.0083, respectively, Fishers exact test). Moreover, there were statistically signicant trends for the two groups at T2 and T4 (P = 0.009 and P = 0.026, respectively, CochranArmitage Trend test), indicating that not only was race an independent inuence affecting the N stage of the

Methods
The study was based on retrospective analysis of medical records of all the patients with a diagnosis of NPC who were seen in Auckland Regional Head and Neck Unit, between the years 1995 and 2007 inclusive. Those patients who had a diagnosis of NPC made before the year 1995 or had the initial diagnosis made at another centre were excluded. Therefore, only those patients presenting with a previously undiagnosed NPC, and who had their initial investigations and work up performed in Auckland, were included. The data regarding patients ethnic and gender demographics were acquired from the Concerto and PiMS databases, used throughout the Auckland region. The ethnicity Asian does not include Indian or Sri Lankan as a subset, but rather encompasses Chinese, immigrants from Hong Kong, Taiwan, Korea, Vietnam, Japan and Philippines. For parts of the analysis, the MPI patients were considered as one, and their results were compared with that of the Asian population. Although Maori are a distinct ethnicity native to New Zealand, they can be classied as Pacic Islanders in origin. Similarly, the Asian population was not divided into the different ethnicities for the purpose of analysis. The initial investigations included a computed tomography (CT) scan or a magnetic resonance imaging (MRI) scan, or both. After imaging, all patients underwent a biopsy from the primary tumour to establish a denitive diagnosis. The reports of the imaging investigations were reviewed, and each patient was retrospectively staged according to the revised American Joint Committee on Cancer (AJCC) staging criteria published in 2002. Like the TNM classication of each patient, the location of nodal disease within the neck was recorded as per the standard ve neck levels. The N stage at presentation was analysed according to the nodal level of the disease in the neck (N0-N3a/b), the T stage and ethnicity. The distribution of nodal disease at presentation was analysed by ethnicity, T stage and the presence of nodal disease as none, unilateral or bilateral. The latter looked for a trend of an ethnicity to present with more bilateral nodal neck disease than another. To compare the differences in T stage of the disease between MPI and Asians, the Fisher exact test was used over the chi-squared test, as one better suited for small population sizes. For the same reason, the T2a and T2b stages were analysed together as T2. The CochranArmitage Trend test was used to test for the presence of a trend between groups.
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Ianovski et al.

60
7

50
14

T4 T3 T2

Number of patients

40

30

19

22

T1

20
8 6 1 6 1 8 3
Pacific Islanders
Pacific Islanders 22 8 8 3

10

18

0
Asians
Asians T4 T3 T2 T1 7 14 19 18

4 3 4 3
European
European 4 3 4 3

1
Indian
Indian 0 0 1 0

Maori
Maori 6 1 6 1

Ethnicity

Fig. 1. T stage at presentation.

Table 1 Nodal disease at presentation Asians Unilateral 10 9 5 3 MPI Unilateral 0 4 3 6 Statistical analysis Fishers exact test P P P P = = = = 0.12 0.017 1.0 0.20

None T1 T2 T3 T4 2 7 4 3

Bilateral 6 3 5 1

None 1 1 2 7

Bilateral 3 9 4 15

MPI, Maori and Pacic Island.

Table 2 N Stage at presentation Asians N0 N1 N2 N3 N0 N1 MPI N2 N3 Statistical Analysis Fishers CochranArmitage exact test Trend test P P P P = = = = 0.25 0.046 0.72 0.0083

T1 T2 T3 T4

2 7 4 3

8 7 2 3

4 2 4 1

4 2 4 0

1 1 2 7

0 3 3 1

2 6 3 10

1 4 1 10

P = 0.009 P = 0.026

MPI, Maori and Pacic Island.

disease at diagnosis, but also that MPIs have a more advanced N stage of the disease at diagnosis compared with their T stagematched Asian counterparts. At stages T1 and T3, the difference was not statistically signicant (P = 0.25 and P = 0.72, respectively, CochranArmitage Trend test). Due to the small numbers of distant metastasis at presentation, it was not possible to establish whether there was a statistically signicant difference between the groups.

Discussion
To our knowledge, the current study is the rst to investigate the differences in the presentation of NPC between different ethnic groups in the New Zealand setting. The ndings suggest that, although MPIs and Asians share a common genetic susceptibility to NPC, the nature of the disease at presentation between the two ethnic groups differs signicantly. The studys MPI patients with
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NPC present with a greater T stage at the time of diagnosis, compared with the Asian NPC patient population. When considering the genetic susceptibility that the two ethnicities share, this indicates that there may be environmental factors affecting the volume of the primary tumour at diagnosis. This has implications in the strategies that aim to prevent, diagnose and treat the disease in both MPIs and Asians. One explanation is that the MPI population presents at a later stage of the disease because of differences in education and awareness of the disease, socio-economic status and geographic distribution between the two groups. Another possibility is that there is a difference in the nature of the disease itself: either the biology of the cancer had changed through the different evolutionary pressures applied to the two ethnic groups, or there are environmental factors making NPC nodal spread more aggressive in the MPI population. NPC is well known to be more prevalent in the Asian population, but the high incidence in the MPI population is not widely recognised. It is important for the primary healthcare provider to be aware of the increased risk of NPC in the MPI patient group in order to identify the disease at an early stage. The public awareness of the increased risk of the disease is also an important factor affecting the time of presentation. Multiple studies are published on NPC in the Asian population, and population-based screening has been trialled in China and Taiwan,8 thus leading to increased awareness of the risk of the disease in the population. Overall, both New Zealand doctors as well as the general MPI population need to be educated regarding the increased risk of NPC in the MPI population in order to diagnose the disease early in this subset of population. An earlier study by our unit identied the four cardinal symptoms/signs that signify NPC: cervical lymphadenopathy, middle ear effusion, nasal obstruction and epistaxis. These four account for more than 95% of all NPC presentations.10 Maori are disproportionally over-represented in the in lower socio-economic strata in New Zealand.11 As such, this group has a poorer access to healthcare, and worse overall health outcomes in terms of both morbidity and mortality.12,13 The higher distribution of Maori compared with the Asian population in the rural parts of New Zealand similarly may affect access to healthcare, and predispose to a greater stage of the disease at presentation. These ethnic inequalities in New Zealand health are currently being addressed by New Zealand Health Strategy and the Reducing Inequalities policy which are both working through the development of Maori Health Strategy and the Pacic Health and disability Action Plan.14 There are two main classifying systems used around the world for the staging of NPC. Hos system developed by John Ho in 1960s,15 is frequently used in Asia, while in Europe and United States, the AJCC staging system is preferred. The AJCC staging system has been revised in 1997 and 2002, and is the system used in New Zealand centres. Despite the revision of the systems, the criteria used for the staging remained unchanged. The difference in the nodal stage of the disease at presentation between the MPI and Asian populations, when matched for their respective T stage, prompts further investigations into which of the two staging systems is best applied to the New Zealand MPI population, for grading and treatment decisions.
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Conclusion
Ethnicity is found to be an independent inuence on the primary NPC tumour volume at presentation, with MPI patients presenting with more advanced T stage of the disease compared with the Asian patients. This indicates that an improvement in the awareness of an increased incidence of NPC and in the MPI population, as well as the diseases early symptoms, is needed among the primary healthcare providers and the MPI population of New Zealand. MPI patients present with more advanced nodal disease compared with the Asian population, at similar T stage of the cancer. This nding is statistically signicant at T2 and T4 stages and requires further investigation.

References
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