Auris Nasus Larynx 38 (2011) 244–249

www.elsevier.com/locate/anl

Epidemiological analysis of nasopharyngeal carcinoma in the central

region of Japan during the period from 1996 to 2005
Yuichi Kimura a, Dai Suzuki a, Takahiro Tokunaga a, Tetsuji Takabayashi a,
Takechiyo Yamada a, Naohiro Wakisaka b, Tomokazu Yoshizaki b,
Hideyuki Murata c, Koki Miwa c, Hideo Shoujaku d, Yukio Watanabe d,
Nansei Yamada e, Yatsuji Ito e, Atsushi Yuta f, Kazuhiko Takeuchi f,
Seiji Hosokawa g, Hiroyuki Mineta g, Yasuhisa Hasegawa h,
Yasushi Fujimoto i, Tsutomu Nakashima i,
Shigeharu Fujieda a,*
a
Department of Otorhinolaryngology, Head and Neck Surgery, University of Fukui, Japan
b
Department of Otolaryngology, Head and Neck Surgery, Kanazawa University Graduate School of Medical Science, Japan
c
Department of Otolaryngology, Kanazawa Medical University, Japan
d
Department of Otolaryngology, Head & Neck Surgery, University of Toyama, Japan
e
Department of Otolaryngology, Gifu University Graduate School of Medicine, Japan
f
Department of Otorhinolaryngology, Head and Neck Surgery, Mie University Graduate School of Medicine, Japan
g
Department of Otolaryngology, Hamamatsu University School of Medicine, Japan
h
Department of Head and Neck Surgery, Aichi Cancer Center, Japan
i
Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Japan
Received 22 January 2010; accepted 29 July 2010

Abstract

Objective: It has become clear through epidemiological analysis that the incidence of cancers of the lung, liver, colon, and rectum are
increasing in Japan every year. However, there have been few epidemiological analyses of nasopharyngeal carcinoma (NPC) in Japan. The
aim of this study was to analyze the epidemiology and current incidence of NPC in the Chubu region of Japan during the period from 1996 to
2005.
Methods: Takeshita et al. conducted a similar investigation in the Chubu region 10 years ago, and, as a result, this is a comparative study. The
Chubu region is the central region of Japanese main island. We researched NPC patients treated in hospitals in each prefecture over a 10-year
period (1996–2005) using a questionnaire.
Results: A total of 525 cases (male:385, female:134, unknown:6) were analyzed epidemiologically, histologically, serologically, and
clinically in this study. The incidence per 105 population per year was 0.29. For the period of 1986–1995, the age-standardized
incidence of NPC was 0.28 per 105 persons per year in Takeshita’s report. There was no significant difference between the two periods.
The ages of the patients ranged from 13 to 90 years. The mean age of was 55.2 years. On the basis of the World Health Organization
(WHO) histological criteria, 36% of the patients were classified as WHO I, 27% as WHO II, and 37% as WHO III. Carcinoma was
located in the posterosuperior region in 56%, lateral in 41%, and inferior in 3%. Tumor staging showed that 6% to belonged to stage I,
25% to stage II, 31% to stage III, and 38% to stage IV. A neck mass was present in 52% of the patients, ear symptoms in 48%, nasal
symptoms in 27%, headaches in 10%, pharyngeal symptoms in 9%, ophthalmologic symptoms in 9%, and cranial neurological
symptoms in 9%. The positive rates of serum titers of the antibodies to Epstein-Barr virus (EBV)-related antigens were calculated. The
positive rate of anti-EBV-viral capsid antigen (VCA) immunoglobulin (Ig) G titers was 58.6%, that of anti-EBV-VCA IgA titers was

* Corresponding author at: Department of Otorhinolaryngology, University of Fukui, 23 Shimoaizuki, Matsuoka, Yoshida, Fukui 910-1193, Japan.
Tel.: +81 776 61 8407; fax: +81 776 61 8118.
E-mail address: sfujieda@u-fukui.ac.jp (S. Fujieda).

0385-8146/$ – see front matter # 2010 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.anl.2010.07.006
 Y. Kimura et al. / Auris Nasus Larynx 38 (2011) 244–249
53.6%, and that of EBNA was 81%. The five-year survival rate for all patients was 67.6%, and that for those in stage I, II, III, and IV was
75%, 84%, 69%, and 53%, respectively. The five-year survival rate for stage IV was significantly lower than those for the other stages
(P < 0.05).
Conclusion: The age-standardized annual incidence of NPC in our survey was 0.29 per 105 persons per year, being relatively low and stable.
# 2010 Elsevier Ireland Ltd. All rights reserved.
Keywords: NPC; Epidemiology; Chubu region of Japan
1. Introduction
Cause of mortality have changed markedly along with the
economic boom and public health development in Japan.
Malignant neoplasm has been the leading cause of death in
Japan since 1981. There has been a decreasing trend in
cancers of the stomach and cervix uteri, while an increasing
trend has been observed for cancers of the lung, liver, colon,
and rectum. However, epidemiological analyses have not
been performed for nasopharyngeal carcinoma (NPC) in
Japan except for Sawaki’s report in 1979 [1] and Takeshita’s
report in 1999 [2]. The present incidence of NPC is unclear.
The vast majority of NPC cases were squamous cell
carcinomas, and this was in accordance with the findings of
studies conducted in Europe and the United States. NPC is
an epithelial tumor of the nasopharynx that shows marked
variations between different ethnic populations [3–6].
Epidemiological studies suggested a multifactorial etiology
of NPC involving infection by EBV [7–9], a genetic
predisposition [10,11], environmental factors [12–14], such
as the consumption of salted fish, and other unknown factors.
NPC is a rare cancer in most parts of the world, with an
incidence of less than 1 per 105 persons per year. However, it
is a common cancer in Southern China (incidence of about
12–15 per 105 persons per year) and Southeast Asian
countries such as Indonesia, Malaysia, Thailand, and
Vietnam [3,15–17]. According to Sawaki’s report of 1979
in Japan [1], the age-standardized annual incidence of NPC
in Japan was about 0.20 per 105 persons per year. However,
according to Takeshita’s report covering 1986–1995 in
Chubu, the age-standardized annual incidence was 0.28, and
so the incidence has increased significantly [2]. The Chubu
region is the central region of Japanese main island. The aim
of this study was to clarify the incidence of NPC in Japan,
and compare the incidence and describe the characteristics
over a period of 10 years from 1996 to 2005.
2. Subjects and methods
All cases included in this study are from records of the
hospitals in the seven prefectures (Toyama, Ishikawa, Fukui,
Gifu, Shizuoka, Aichi, and Mie) the Chubu region of Japan.
The Chubu region is one of eight Japanese districts that are
located in the central part of the Japanese mainland. The
average population is 1,111,763 in Toyama, 1,177,031 in
Isikawa, 824,282 in Fukui, 2,103,804 in Gifu, 3,765,073 in
Shizuoka, 7,061,384 in Aichi, and 1,854,262 in Mie. We
245
researched NPC patients treated in 35 hospitals over a 10-year
period (1996–2005) using a questionnaire. Selected hospitals
were key hospitals that are recommended for the medical
treatment of cancer by the Ministry of Health, Labour and
Welfare in Japan. The case definition for this study was being
diagnosed for the first time in each hospital during the period
from 1996 to 2005. Those included in this study were all
patients with histologically proven primary malignant tumors
of the nasopharynx. Tumors diagnosed as the reappearance of
a previously treated tumor (recurrence or metastasis) were
excluded. The method used is a description of the variables
included: sex, age, site, histological type, stage, clinical
symptoms, and the five-year survival rate.
2.1. Statistical analysis
The total number of cases and number of cases according
to the sex, age, site, histological type, stage, and clinical
symptoms of the nasopharynx were analyzed using
Microsoft Excel Software. The level of significance between
various parameters was assessed using the x2 test to obtain
P-values. A significant difference was indicated by a P-value
<0.05. Survival curves were constructed using the method
of Kaplan–Meier.
3. Results
3.1. Number of NPC cases
The total number of NPC cases reported in the Chubu
region during the 10-year period between 1996 and 2005 was
525. No significant differences were detected among years.
Three hundred and eighty-five were male and 134 were
female. The gender of 6 cases was unknown. Significantly
more males than females were diagnosed with NPC, with a
male: female ratio of 2.9:1 (P < 0.05). Fig. 1 shows the
number of NPC cases according to the age at diagnosis. The
age ranged from 13 to 90 years, and the mean age at diagnosis
was 55.2 years.
3.2. Age-standardized annual incidence of NPC per 105
persons
The total population in the 7 prefectures of Chubu was
17,897,600. The age-standardized incidence of NPC for the
period of 1996–2005 was 0.29 per 105 persons per year. For
[(Fig._1)TD$IG]
246
Y. Kimura et al. / Auris Nasus Larynx
Fig. 1. Number of patients by age group.
the period of 1986–1995, the age-standardized incidence of
NPC was 0.28 per 105 persons per year. There was no
significant difference between the two periods.
3.3. Patients classified histologically according to the
World Health Organization
The percentage classified as WHO I (keratinizing
squamous cell carcinoma) was 36%, that as WHO II
(nonkeratinizing squamous cell carcinoma) was 27%, and
that as WHO III (undifferentiated carcinoma or lymphoe-
pithelioma) was 37%.
3.4. Patients classified according to the tumor origin
and stage
The rate of tumors that originated from an inferior site was
3%, with 41% from a lateral site, and 56% from a
posterosuperior site. Six percent (32 cases) of cases belonged
to stage I, 25% (124 cases) to stage II, 31% (158 cases) to stage
III, and 38% (191 cases) to stage IV.
3.5. Clinical symptoms
The distribution of symptoms is shown in Fig. 2. The
clinical symptoms of 507 patients were examined. Otological
symptoms were noted in 242 (48%) patients, nasal symptoms
in 138 (27%), pharyngeal symptoms in 46 (9%), ophthalmo-
logic symptoms in 37 (9%), cranial neurological symptoms in
44 (9%), headaches in 51 (10%), 260 (52%) had cervical
lymph node swelling, and there were other symptoms in 26
[(Fig._2)TD$IG](4%). Otological symptoms included hearing disturbance and
Fig. 2. Prevalence of clinical signs.
[(Fig._3)TD$IG]
38 (2011) 244–249
Fig. 3. Kaplan–Meier survival curves for NPC by tumor stage.
a sensation of ear fullness due to otitis media with effusion
(OME). Nasal symptoms included nasal obstruction and nasal
bleeding. For cranial neurological symptoms, the abducent
nerve (cranial nerve VI) is the most subject to impairment and
the trigeminal nerve (V) the second most.
3.6. Positive rates of serum antibodies to Epstein-Barr-
related antigens
We examined serological anti-EBV-VCA IgG titers in a
total of 222 cases. With the aid of histological classifica-
tion according to WHO criteria, we subsequently
calculated positive rates. Of 64 WHO I cases, 37 were
positive (58%), of 61 WHO II cases, 32 were positive
(52%), and of 59 WHO III cases, 39 were positive (66%).
There was no significant difference between WHO
classifications. We also examined serological anti-EBV-
VCA IgA titers from a total of 181 cases. Of 63 WHO I
cases, 34 were positive (54%), of 59 WHO II cases, 33
were positive (56%), and of 59 WHO III cases, 30 were
positive (51%). There was no significant difference
between WHO classifications. According to EBNA, we
examined a total of 141 cases. One hundred and fourteen
cases were positive (81%).
3.7. Causes of death
Of the 137 patients who died of NPC, the causes of death
were determined. Intracranial invasion comprised 36%,
organ metastasis 36%, lymph node metastasis 6%, and other
reasons 16%.
3.8. Analysis of 5-year survival trends for NPC
The Kaplan–Meier survival curves by tumor stage are
presented in Fig. 3. The 5-year survival rate for all patients
was 67.6%, and those in stage I, II, III, and IV were 75, 84%,
69%, and 53%, respectively. The 5-year survival rate for
stage IV was significantly lower than those in the other
stages (P < 0.05).
 Y. Kimura et al. / Auris Nasus Larynx 38 (2011) 244–249
4. Discussion
We investigated various epidemiological parameters
related to NPC in the Chubu region, comprising about 18
million people (14% of the total Japanese population), over
the 10-year period of 1996–2005, and 525 patients were
histologically confirmed to have NPC. Reviewing the
literature failed to yield any population-based data regarding
the incidence and follow-up of NPC in Japan. The scale of our
investigation is large in Japan since Sawaki’s and Takeshita’s
reports. In addition, this report represents the first study
involving a follow-up survey in Japan. The age-standardized
annual incidence of NPC in our survey was 0.29 per 105
persons per year. However, it was about 0.20 per 105 persons
per year in Sawaki’s reports and 0.28 in Takeshita’s report,
showing that the incidence has increased significantly [1,2].
However, it was 0.28 per year during 1986–1995, so it hardly
changed over the 10 years in this investigation.
The incidence of NPC has a rather distinct and
geographically well-defined distribution worldwide. NPC
is a rare malignancy in most parts of the world, with age-
adjusted incidences under 1 per 105 persons per year for both
men and women. In certain geographical regions, however,
the incidence of NPC is markedly higher. High to
intermediate rates are observed in certain populations and
regions in China, Southeast Asia, and Northern Africa,
among the Inuit populations of Alaska, Greenland, and
Northern Canada, and in migrants of Chinese and Filipino
descent. The reported rates are 25–30 per 105 persons per
year in Southeastern China and Hong Kong and 13.22 per
105 persons per year in Taiwan [3,4]. In all studies published
until now, including the present one, men were shown to
have NPC more frequently than women. Thus, in high-risk
populations, the sex ratio (men in comparison to women)
was 2.6:1 in Hong Kong and 3.1:1 in Taiwan. According to
data from the ‘‘Japan’’ study, which included new patients
suffering from NPC during the period 1986–1995, 73% of
all patients with NPC were men, and 27% were women,
which is similar to our results (74% men and 26% women).
Adolescent NPC patients are sometimes treated, but it is
rare that we treat young patients with other head and neck
cancers (HNCA), such as laryngeal and maxillary cancer. In
the literature, many young patients have been reported
[3,16]. In our study, 37 cases were younger, aged 10–29. The
mean age at diagnosis of NPC in our study was 55.2 years,
being lower than that of other head and neck cancers. The
peak age was 50–59 years for this cancer, although the peak
was 60-year old or more in most other cancers.
Of recent interest has been the relationship of the
pathologic subtype. In the WHO system, the first two groups
of NPC are moderately differentiated squamous cell
carcinomas with keratin production (type I) or nonkeratiniz-
ing (type II), with a third group comprising undifferentiated
carcinomas or lymphoepitheliomas (type III). Type I is more
common in low-incidence populations, markedly greater
than in endemic areas [3]. In areas of high-incidence
247
populations which include Southern China and Southeast
Asia, EBV is strongly associated with NPC. Most patients
have poorly or undifferentiated (WHO type II or type III)
carcinoma. Types II and III are more commonly associated
with an elevated EBV titer, with EBV detection in type I
being less consistent. In areas of high-incidence populations,
NPC patients showed a high level of serum EBV IgG and
IgA antibodies. These findings are in agreement with many
published reports and our results. Furthermore, EBV is a
leading risk factor in highly endemic regions of NPC like
Southeast Asia which might accelerate the NPC incidence,
making the mean age of NPC in highly endemic regions less
than that in Western countries, where EBV is less frequently
associated with NPC [5–8].
Cancer is a disease of multifactorial etiology involving
environmental and genetic factors. The genetic suscept-
ibility is best measured by the family history of the disease.
Several susceptibility related genes have already been
implicated in the etiology of NPC, such as certain alleles of
human leukocyte antigen (HLA) classes I and II [10–12].
However, NPC patients showed the lowest rate of a positive
family history of the disease among HNCA. Statistical
analysis clarified that NPC was significantly associated with
a negative family history of the disease, while other HNCA
types were significantly associated with a positive family
history. Smoking proved to be an important risk factor for
the development of HNCA. The number of regular smokers
among NPC patients was much higher [15,16]. In addition,
the EBV serum level of both IgG and IgA antibodies was
significantly higher in regular smokers with NPC than in
non-regular smokers. This refer to a possible link between
smoking and EBV in respect to the NPC etiology or
propagation. This points out the possibility that cigarette
smoke components are one of the factors causing EBV
reactivation within the nasopharyngeal mucosa. Unlike for a
smoking habit, the percentage of regular alcohol consumers
in HNCA patients was not significantly higher, except for
NPC patients, who showed a markedly higher percentage of
regular alcohol consumers than other HNCA types. This
provided evidence that alcohol consumption acts as one of
the important risk factors for NPC.
In terms of the site of NPC, it was posterosuperior in 56%
of the cases, lateral in 41% and inferior in 3%. According to
Takeshita’s reports, it has accounted for 90% by poster-
osuperior and lateral site [2]. By the difference of the site of
origin, how of the symptom for appearance is different, so it
is very important to diagnose the site of origin of NPC.
Because there is comparatively much that it occurs in
posterosuperior and lateral, it seems that there are many
appearances of otological sign and nasal sign. As for clinical
symptoms, the symptom seen in high frequency as well as
cervical lymph node swelling was otological symptoms
[1,2]. So that their results were almost the same as ours. The
otological symptoms include hearing disturbance and a
sensation of ear fullness due to otitis media effusion.
Therefore, we must carefully examine the nasopharynx
248 Y. Kimura et al. / Auris Nasus Larynx 38 (2011) 244–249
when treating patients of otitis media effusion. However, as
for the nasopharynx, examination is difficult for the
restricted space and because the subjective symptoms do
not appear unless a tumor grows to some degree, the early
diagnosis is difficult. Therefore, it followed that there was
much advanced cancer of stage III and stage IV with 69% in
our results and 87% in Takeshita’s reports.
This disease paradigm would greatly benefit from a
screening tool or biomolecular marker that could detect the
presence of cancer in asymptomatic patients [18,19]. EBV is
believed to be closely associated with NPC since the viral
genomes are regularly found in NPC biopsies by DNA
hybridization, and EBV-related antigens have been demon-
strated in the tumor cells of NPC. EBV is ubiquitous in NPC,
with cells containing multiple copies of the EBV genome
regardless of the histology or differentiation. Prior research
has demonstrated that cell-free EBV DNA can be
quantitatively measured in the blood of NPC patients using
the polymerase chain reaction (PCR) technique [20]. PCR
may become an ideal tool for guiding the diagnostic workup
in the challenging area of occult primary tumors, facilitating
an earlier diagnosis and reducing morbidity and mortality.
Although there are many markers for the clinical diagnosis
of nasopharyngeal carcinoma (NPC), the efficacy of most of
them for an early diagnosis is poor. According to a recent
paper, compared to the routine parallel sequential test,
logistic regression in combination with multiple diagnostic
tests achieved a higher diagnostic specificity and sensitivity
for NPC. Two optimal combinations were EBV
DNA + EBNA1/IgA and VCA/IgA + EBNA1/IgA. Adopt-
ing logistic regression in combination with multiple
diagnostic tests and using the probability prediction to
decide on the cut-off value may help increase the diagnostic
sensitivity and specificity for NPC [21].
Radiotherapy is the mainstay of treatment, and is an
essential component of curative-intent treatment of non-
disseminated NPC. Stage I and II diseases are treated by
radiation therapy alone. Stage III-IV disease is treated by
radiation therapy with concurrent cisplatin followed by
adjuvant chemotherapy with cisplatin and fluorouracil [22].
In the Chubu region, the treatment of NPC varies among
hospitals. However, the standard treatment for NPC mainly
involves radiation therapy and chemotherapy. If neck lymph
nodes metastasis persists, neck dissection is performed. The
5-year survival rate for stage IV was significantly lower than
that in other stages. Patients with early-stage NPC show a
markedly improved survival compared with those diagnosed
in later disease stages. Furthermore, the primary tumor
volume shows a closer relationship with the survival rates of
NPC patients [23,24]. The early detection of NPC should
improve the cure rate and reduce morbidity and metastasis
[25,26]. Unfortunately, NPC is often difficult to diagnose
because of the non-specific nature of its clinical symptoms
and the difficulty in visualizing the nasopharynx. Most NPC
tumors remain undiagnosed until metastasis to the cervical
lymph nodes occurs, often without an overt pathology at the
primary site which indicates the desperate need for an early
diagnosis and early treatment strategies to improve survival.
NPC is highly radiosensitive, and therefore, radiotherapy
and radiotherapy combined with chemotherapy are the main
treatment strategies. However, a high dose of radiation
damages normal tissue and renders the NPC cells resistant to
radiation, resulting in incomplete cure and the recurrence of
the tumor. Further, the addition of platinum-based che-
motherapy improves disease control, but it is associated with
marked early and late toxic effects. The toxic effects after
chemoradiotherapy for NPC decrease the QOL over the long
term, such as causing swallowing difficulties, sense-related
problems, dry mouth, dental problems, and fatigue [27].
Therefore, the consensus of radiation therapy is that a total
dose of 70 Gy is needed for eradication of gross tumor and
50–60 Gy for elective treatment of potential risk sites, but to
minimize the risk of late toxicity, fractional dose >2 Gy per
daily fraction and excessive acceleration with multiple
fractions >1.6 Gy/fraction should be avoided. In addition,
chemotherapy should be considered for patients with
adequate performance status. On the other hand, scientists
have made every effort to develop an effective method to kill
tumors while keeping the dose of radiation as low as
possible. Recently, gene therapy that can effectively enhance
nasopharyngeal carcinoma sensitivity to radiotherapy has
been reported [28–30]. For the improvement of treatment
results, as for the early detection of cancer, the development
of gene therapy is hoped for in the future.
5. Conclusion
The age-standardized incidence of NPC for the period of
1996–2005 was 0.29 per 105 persons per year. For the period
of 1986–1995, the age-standardized incidence was 0.28 per
105 persons per year, and so it was relatively low and stable.
Acknowledgements
We wish to thank the presidents of the prefectual
otorhinolaryngologist groups for supporting this epidemio-
logical research on NPC.
References
[1] Sawaki S. The basic and clinical study of nasopharyngeal carcinoma.
Nippon Jibiinkoka Gakkai Kaiho 1979;82:1345–51. Japanese.
[2] Takeshita H, Furukawa M, Fujieda S, Shoujaku H, Ookura T, Sakaguchi
M, et al. Epidemiological research into nasopharyngeal carcinoma in the
Chubu region of Japan. Auris Nasus Larynx 1999;26:277–86.
[3] Bay F, Haugen M, Moger TA, Tretli S, Aalen OO, Grotmol T. Age-
incidence curves of nasopharyngeal carcinoma worldwide: Bimodali-
ty in low-risk populations and aetiologic implications. Cancer Epide-
miol Biomarkers Prev 2008;17:2356–65.
[4] Chen MC, Feng IJ, Lu CH, Chen CC, Lin JT, Huang SH, et al. The
incidence and risk of second primary cancers in patients with naso-
 Y. Kimura et al. / Auris Nasus Larynx 38 (2011) 244–249
pharyngeal carcinoma: a population-based study in Taiwan over a 25-
year period (1979–2003). Ann Oncol 2008;19:1180–6.
[5] Anandan C, Elton R, Hitchings A, Brewster DH. Nasopharyngeal
cancer incidence and survival in Scotland, 1975–2001. Clin Otolar-
yngol 2008;33:12–7.
[6] Nesic V, Sipetic S, Vlajinac H, Miljus D, Stosic-Divjak S, Jesic S.
Incidence of nasopharyngeal carcinoma in Belgrade during the period
1991–2005. Vojnosanit Pregl 2009;66:473–6.
[7] Yap YY, Hassan S, Chan M, Choo PK, Ravichandran M. Epstein-Barr
virus DNA detection in the diagnosis of nasopharyngeal carcinoma.
Otolaryngol-Head Neck Surg 2007;136:986–91.
[8] Guo X, Johnson RC, Deng H, Liao J, Guan L, Nelson GW, et al.
Evaluation of nonviral risk factors for nasopharyngeal carcinoma in
a high-risk population of Southern China. Int J Cancer 2009;124:
2942–7.
[9] Ling W, Cao SM, Huang QH, Li YH, Deng MQ. Prognostic implica-
tion of pretreatment titer of serum immunoglobulin A against Epstein-
Barr virus capsid antigen in nasopharyngeal carcinoma patients in
Sihui, Guangdong. Chin J Cancer 2009;28:57–9.
[10] Lu SJ, Day NE, Degos L, Lepage V, Wang PC, Chan SH, et al. Linkage
of a nasopharyngeal carcinoma susceptibility locus to the HLA region.
Nature 1990;346:470–1.
[11] Yu KJ, Gao X, Chen CJ, Yang XR, Diehl SR, Goldstein A, et al.
Association of human leukocyte antigens with nasopharyngeal car-
cinoma in high-risk multiplex families in Taiwan. Hum Immunol
2009;13.
[12] Yu KJ, Hsu WL, Chiang CJ, Cheng YJ, Pfeiffer RM, Diehl SR, et al.
Cancer patterns in nasopharyngeal carcinoma multiplex families in
Taiwan. Int J Cancer 2009;124:1622–5.
[13] Zheng X, Yan L, Nilsson B, Eklund G, Drettner B. Epstein-Barr virus
infection, salted fish and nasopharyngeal carcinoma. Acta Oncologica
1994;33:867–72.
[14] Gallicchio L, Matanoski G, Tao XG, Chen L, Lam TK, Boyd K, et al.
Adulthood consumption of preserved and nonpreserved vegetables
and the risk of nasopharyngeal carcinoma: a systematic review. Int J
Cancer 2006;119:1125–35.
[15] Abdulamir AS, Hafidh RR, Abdulmuhaimen N, Abubakar F, Abbas
KA. The distinctive profile of risk factors of nasopharyngeal carcino-
ma in comparison with other head and neck cancer types. BMC Public
Health 2008;8:400.
[16] Chen CJ, You SL, Lin LH, Hsu WL, Yang YW. Cancer epidemiology
and control in Taiwan: a Brief review. Jpn J Clin Oncol 2002;32:
66–81.
249
[17] d’Espiney Amaro C, Montalvao P, Henriques P, Magalhaes M, Olias J.
Nasopharyngeal carcinoma: our experience. Eur Arch Otorhinolar-
yngol 2009;266:833–8.
[18] Cui C, Liu L, Ma J, Liang S, Tian L, Tang L, et al. Trigeminal nerve palsy
in nasopharyngeal carcinoma: correlation between clinical findings and
magnetic resonance imaging. Head Neck 2009;31: 822–8.
[19] O TM, Yu G, Hu K, Li JC. Plasma Epstein-Barr virus immunoglobulin
A and DNA for nasopharyngeal carcinoma screening in the United
States. Otolaryngol Head Neck Surg 2007;136:992–7.
[20] Chan KCA, Lo YMD. Circulating EBV DNA as a tumor marker for
nasopharyngeal carcinoma. Cancer Biol 2002;12:489–96.
[21] Jiang SQ, Liu Q. Application of logistic regression in combination
with multiple diagnostic tests for auxiliary diagnosis of nasopharyn-
geal carcinoma. Chin J Cancer 2009;28:177–80.
[22] Chan AT, Felip E. Nasopharyngeal cancer: ESMO clinical recom-
mendations for diagnosis, treatment and follow-up. Ann Oncol
2008;19:81–2.
[23] Lee CC, Ho HC, Lee MS, Hsiao SH, Hwang JH, Hung SK, et al.
Primary tumor volume of nasopharyngeal carcinoma: significance for
survival. Auris nasus Larynx 2008;35:376–80.
[24] Shen C, Lu JJ, Gu Y, Zhu G, Hu C, He S. Prognostic impact of primary
tumor volume in patients with nasopharyngeal carcinoma treated by
definitive radiation therapy. Laryngoscope 2008;118:1206–10.
[25] Sheng L, Shui Y, Shen L, Wei Q. Effect of patient-related delay in
diagnosis on the extent of disease and prognosis in nasopharyngeal
carcinoma. Am J Rhinol 2008;22:317–20.
[26] Xiao WW, Han F, Lu TX, Chen CY, Huang Y, Zhao C. Treatment
outcomes after radiotherapy alone for patients with early-stage naso-
pharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2009;74:1070–6.
[27] Oates JE, Clark JR, Read J, Reeve N, Gao K, Jackson M, et al.
Prospective evaluation of quality of life and nutrition before and after
treatment for nasopharyngeal carcinoma. Arch Otolaryngol Head
Neck Surg 2007;133:533–40.
[28] Xia J, Xia K, Feng Y, Tang A, Tang Y, Wu L, et al. The combination of
suicide gene therapy and radiation enhances the killing of nasopha-
ryngeal carcinoma Xenographs. J Radiat Res 2004;45:281–9.
[29] Jiang W, Liao Y, Zhao S, Wu B, Zhou R, Wei R, et al. Role of enhanced
radiosensitivity and the tumor-specific suicide gene vector in gene
therapy of nasopharyngeal carcinoma. J Radiat Res 2007;48:211–8.
[30] Pan JJ, Zhang SW, Chen CB, Xiao SW, Sun Y, Liu CQ, et al. Effect of
recombinant adenovirus-p53 combined with radiotherapy on long-
term prognosisof advanced nasopharyngeal carcinoma. J Clin Oncol
2009;27:799–804.