The Laryngoscope

C 2013 The American Laryngological,

V

Rhinological and Otological Society, Inc.

Association of Rhinosinusitis With Nasopharyngeal Carcinoma:

A Population-Based Study
Shih-Han Hung, MD; Po-Yueh Chen, MD; Herng-Ching Lin, PhD; Jonathan Ting, BS;
Shiu-Dong Chung, MD, PhD
Objectives/Hypothesis: Although it is already known that the inflammation process elevates the risk of developing cancer, to date the association between rhinosinusitis and nasopharyngeal carcinoma (NPC) remains unknown. This study aimed
to evaluate the association between rhinosinusitis and NPC based on a nationwide database.
Study Design: Case-control study.
Methods: In total, the cases comprised of 2,242 subjects with NPC and 6,726 randomly selected subjects as controls.
Separate conditional logistic regression analyses were used to calculate the odds ratio (OR) for having been previously diagnosed with chronic and acute rhinosinusitis between the cases and controls.
Results: Of the total sample, 607subjects (6.77%) had been diagnosed with chronic rhinosinusitis prior to the index
date: 322 (14.36%) cases with NPC and 285 (4.24%) controls (P <.001). A conditional logistic regression analysis revealed
that the OR of prior chronic rhinosinusitis for subjects with NPC is 3.83 (95% confidence interval [CI], 3.23-4.53) as compared to controls after adjusting for the factors of income, urbanization, geographic location, tobacco use disorder, and alcohol
abuse/dependence syndrome. Furthermore, 1,199 (53.48%) cases and 2,938 (42.19%) controls had been diagnosed with
acute rhinosinusitis prior to the index date (P <.001).The adjusted OR of prior acute rhinosinusitis for subjects with NPC was
1.57 (95% CI, 1.43-1.73) that of controls.
Conclusions: This study detected an association between NPC and rhinosinusitis. We recommend that patients who are
diagnosed with rhinosinusitis, either acute or chronic, seek out aggressive management to reduce the tissue burden and lower
the risk of subsequently developing NPC.
Key Words: Rhinosinusitis, nasopharyngeal carcinoma.
Level of Evidence: 3b.
Laryngoscope, 124:15151520, 2014

INTRODUCTION
Nasopharyngeal carcinoma (NPC) accounts for
80,000 incident cases and 50,000 deaths worldwide
annually.1 It is unique because of its high prevalence in
the Chinese populations. The male-to-female ratio for an
NPC diagnosis is approximately 2 to 3:1. The incidence
of NPC in the Chinese population is known to be significantly higher as compared to the incidence in the United
States and Japanese populations. Furthermore, secondgeneration Chinese immigrants to the United States are
seven times more likely to develop NPC as compared to

From the Department of Otolaryngology (S.-H.H.), Taipei Medical

University Hospital; Department of Otolaryngology (P.-Y.C.), Taipei Medical University-Shuang Ho Hospital; Sleep Research Center (H.-C.L-D.C.),
Taipei Medical University Hospital; School of Medical Laboratory Sciences and Biotechnology (H.-C.L.), Taipei Medical University, Taipei, Taiwan; School of Health Sciences (J.T.), Purdue University, West Lafayette,
Indiana, U.S.A; Division of Urology (S.-D.C.), Department of Surgery, Far
Eastern Memorial Hospital, New Taipei City, Taiwan.
Editors Note: This Manuscript was accepted for publication
September 13, 2013.
The authors have no funding, financial relationships, or conflicts
of interest to disclose.
Send correspondence to Shiu-Dong Chung, MD, Division of Urology, Department of Surgery, Far Eastern Memorial Hospital, No. 21,
Sec. 2, Nanya S. Rd., Banciao Dist., New Taipei City 220, Taiwan.
E-mail: chungshiudong@gmail.com
DOI: 10.1002/lary.24435

Laryngoscope 124: July 2014

Caucasians.2 According to the latest government cancer

registry data, in Taiwan the annual incidence for nasopharyngeal carcinoma reached 65 per 10,000 population
in 2009.3
Risk factors for the development of NPC are
believed to be age, gender, genomics, ancestry, diet,
Epstein-Barr virus (EBV), alcohol use, and tobacco
use.414 It is not surprising that factors such as alcohol
and tobacco use, which result in direct irritation of the
nasopharynx, would lead to this disease. Even domestic
cooking fume exposures were reported to be associated
with an increased risk of NPC.15 Rhinosinusitis, on the
other hand, is seldom regarded as a significant risk factor associated with NPC.
Rhinosinusitis is a common condition defined as a
symptomatic inflammation of the nasal cavity and paranasal sinuses responsible for over 24 million annual cases
in the United States.16 Acute rhinosinusitis includes disease processes that last for <4 weeks, whereas chronic
rhinosinusitis is defined as symptoms persisting for 12
weeks or longer.17,18 In a study done by Yuan et al., the
authors found that there was an excess number of NPC
patients compared to control patients who had a history
of chronic ear and nose disease.19 Although it is known
that the inflammation process can elevate the risk of cancer, to date the association between the rhinosinusitis
and NPC remains unknown.20,21
Hung et al.: Sinusitis and Nasopharyngeal Carcinoma

1515

The purpose of this study was to evaluate the association of acute and chronic rhinosinusitis with NPC
based on a nationwide database.

year) were also used to calculate the odds ratio (OR) for having
been previously diagnosed with rhinosinusitis between cases
and controls. We adjusted for tobacco use and alcohol abuse/
dependence in the regression models. The conventional P .05
was used to assess statistical significance.

MATERIALS AND METHODS

Database
Data were retrieved from the Longitudinal Health Insurance Database 2000 (LHID2000) released by the Taiwan
National Health Research Institute. Taiwan began a singlepayer National Health Insurance (NHI) program in 1995, and
the program has covered about 98% of the population since its
inauguration. The LHID2000 includes data from all medical
claims of 1 million randomly selected enrollees of all NHI 2000
enrollees. Several studies have demonstrated the high validity
of the data from the NHI program.22,23 Furthermore, hundreds
of studies employing the LHID2000 have been published in
internationally peer reviewed journals.24 Because the database
consists of deidentified secondary data released without conditions to researchers, this study was exempt from a full review
by the institutional review board.

Study Sample
This study was designed as a case-control study. For the
selection of cases, we identified 2,356 subjects who had received
a first-time diagnosis of NPC (International Classification of
Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code
147) in an ambulatory care visit (including outpatient departments of hospitals and clinics) or during hospitalization
between the dates of January 1, 2002 to December 31, 2011.
One hundred fourteen subjects younger than 18 years old were
excluded to limit the study sample to the adult population. In
total, 2,242 subjects with NPC were considered cases in this
study. We assigned the first ambulatory care visit or hospitalization date for a nasopharyngeal carcinoma diagnosis as their
index date.
Likewise, we selected the controls from the LHID2000.
First we excluded all of the subjects who had ever received a
diagnosis of NPC since the initiation of the NHI program in
1995. We then randomly selected 6,726 controls (three controls
per case) to match the cases in terms of gender, age group (18
29, 3039, 4049, 5059, 6069, and >69 years), and index year
through an SAS PROC SURVEYSELECT program (SAS Institute Inc., Cary, NC). For the controls, the year of index date
was simply a matched year in which controls had a medical
visit. In addition, we further assigned the first utilization of
medical care occurring in the index year as the index date.

Exposure Assessment
This study identified rhinosinusitis cases by ICD-9-CM
codes 461 (acute rhinosinusitis) and 473 (chronic rhinosinusitis). Furthermore, this study only included rhinosinusitis cases
who had received a rhinosinusitis diagnosis within 3 years prior
to the index date.

Statistical Analysis
SAS System for Windows version 8.2 (SAS Institute Inc.)
was used for the statistical analyses in this study. Pearson v2
tests were used to examine the differences between cases and
controls on sociodemographic characteristics (monthly income,
urbanization, and geographic location). Conditional logistic
regression analyses (conditioned on sex, age group, and index

Laryngoscope 124: July 2014

1516

RESULTS
The mean sample age was 50.5 years (standard
deviation [SD], 14.7 years); 50.6 years for the cases and
50.4 years the controls (P 5.725). Table I presents the
distributions of the samples sociodemographic characteristics between the cases and controls. It shows that there
was no significant difference between cases and controls
in terms of monthly income, urbanization level, geographic region, tobacco use, and alcohol abuse/
dependence.
The crude and adjusted OR of prior chronic rhinosinusitis is shown in Table II. Of the total sample, 607
subjects (6.77%) had received chronic rhinosinusitis
prior to their index date: 322 (14.36%) subjects with
NPC and 285 (4.24%) controls. The mean periods of time
between the occurrence of rhinosinusitis and onset of
NPC were 1,091 (SD, 964) days, and 702 (SD, 888) and
1,123 (SD, 961) days for subjects who respectively had
chronic and acute rhinosinusitis (not shown in the
tables). Conditional logistic regression analysis (conditioned on sex, age group, and index year) revealed that
the OR of prior chronic rhinosinusitis for subjects with
NPC was 3.83 (95% confidence interval [CI], 3.23-4.53)
that of controls. After adjusting for income, urbanization, geographic location, tobacco use, and alcohol abuse/
dependence, the OR of prior chronic rhinosinusitis for
those with NPC was 3.79 (95% CI, 3.21-4.48) that of
controls.
Table III presents the crude and adjusted OR hazard ratios of acute rhinosinusitis. A total of 1,199
(53.48%) cases and 2,938 (42.19%) controls had acute
rhinosinusitis prior to the index date (P < 0.001). Furthermore, the OR of prior acute rhinosinusitis for subjects with NPC was 1.57 (95% CI, 1.43-1.73) that of
controls after adjusting for income, urbanization, geographic location, tobacco use, and alcohol abuse/alcohol
dependence.
Table IV shows a sensitivity analysis. After excluding subjects who were newly diagnosed with chronic rhinosinusitis within 1 year prior to the index date, the
adjusted OR of prior chronic rhinosinusitis for subjects
with NPC was 3.90 (95% CI, 3.26-4.68) that of controls.

DISCUSSION
In this study we were able to demonstrate that
patients with rhinosinusitis were more likely to have
NPC, and our findings strongly support that rhinosinusitis should be considered as a possible risk factor. In
endemic populations, the risk factors appear to be an
interaction of several factors including EBV infection,
genetic predispositions, and environmental factors such
as the high intake of preserved foods and smoking. It is
also very interesting to note that the exposure to a common agent early in life seems to act as a critical factor.25
Hung et al.: Sinusitis and Nasopharyngeal Carcinoma

TABLE I.
Subjects With Nasopharyngeal Carcinoma and ControlsSociodemographic Characteristics (n 5 8,968).
Nasopharyngeal Carcinoma
Subjects, n 5 2,242
Variables

Controls, n 5 6,726

No.

No.

1,478
764

65.9
34.1

4,434
2,292

65.9
34.1

<30
3039

171
317

7.6
14.1

513
951

7.6
14.1

4049

579

25.8

1,737

25.8

5059
6069

586
345

26.1
15.4

1,758
1,035

26.1
15.4

>69

244

10.9

732

10.9

819

36.5

2,343

34.8

Gender
Male
Female

1.000

Age, yr

Monthly income
<NT$15,841
NT$15,841 NT$25,000

P Value

1.000

.280
805

35.9

2,523

37.5

618

27.6

1,860

27.7

643

28.7

1,937

28.8

2
3

662
384

29.5
17.1

1,930
1,176

28.7
16.4

302

13.5

900

13.4

251

11.2

783

11.6

Northern

1,006

44.9

3,132

46.6

Central
Southern

499
691

22.3
30.8

1,539
1,923

22.9
28.5

Eastern

46

2.1

132

2.0

28

1.3

87

1.3

.871

69

3.1

219

3.2

.678

NT$25,001
Urbanization level

5
Geographical region

Alcohol abuse/alcohol
dependence syndrome
Tobacco use disorder

.312

.234

NT$ 5 New Taiwan dollar.

Findings from previous studies lead to a clinical recommendation that avoiding certain exposures might lead to
a decreased incidence of NPC. The carcinogenic effects
of some of these known environmental risk factors were
understood based on previous knowledge. For instance,
EBV and human papillomavirus were already known for
their molecular level carcinogenic mechanisms.26 The
risk factor of consuming salt-cured food is believed to be
mediated through the releases of volatile nitrosamines
that are carried by the blood steam and distributed over
the nasopharyngeal mucosa.5 Even the carcinogenic
effects behind the use of Chinese medicinal herbs were
considered to contribute, either by reactivating EBV or
through a direct effect on EBV-transformed cells.27 However, none of these pathogenic theories were focused on
the more common phenomenon: inflammation.
The theories connecting the inflammatory process
and carcinogenesis have been proposed for more than a
decade. During the inflammatory process, granulocytes
secrete chemically reactive oxidants, radicals, and
Laryngoscope 124: July 2014

electrophilic mediators to eradicate pathogens. Although

regarded as an effective host defense mechanism, it inevitably exposes the epithelial and connective tissues to certain endogenous genotoxic agents. Whereas in most cases
the genotoxic burdens are reduced by the cell repair mechanisms and become negligible, in long-term cases inflammation eventually elevates the risk of cancer.20 The
theory is well supported by much of the epidemiological
evidence. Probably the best known example is the association between colon cancer and ulcerative colitis. In a large
scale study done by Ekbom et al. involving thousands of
patients, investigators reported a 5.7-fold increase in colon
cancer incidence in patients with chronic ulcerative colitis
as compared to those without.28 More interestingly, the
risk of cancer correlated directly with both the severity
and duration of the disease. Later on, the same group
reported that ulcerative colitis does not increase the risk
of other types of cancer.29 This finding is especially important because it strongly supports the role localized inflammation plays in cancer development.
Hung et al.: Sinusitis and Nasopharyngeal Carcinoma

1517

TABLE II.
Crude and Adjusted Odds Ratios of Prior Chronic Rhinosinusitis Between Nasopharyngeal Carcinoma Subjects and Controls (n 5 8968).
Total Sample, n 5 8,968
Presence of Prior Chronic
Rhinosinusitis

Yes
No
Crude OR (95% CI)

No.

607

6.77

8,361

93.23

Adjusted OR (95% CI)

Nasopharyngeal Carcinoma
Subjects, n 5 2,242
No.

322

14.36

1,920
85.64
3.83* (3.23-4.53)

3.79* (3.21-4.48)

Controls, n 5 6,726
No.

285

4.24

6,441

95.76
1.00
1.00

*P <.001.

Conditional logistic regression conditioned on subjects age and sex, adjusted for monthly income, geographic region, urbanization level, alcohol
abuse/alcohol dependence syndrome, and tobacco use disorder.
CI 5 confidence interval; OR 5 odds ratio.

The same phenomenon can be observed in the lungs

as well. It is reported that patients with asthma showed
a significant excess risk of developing lung cancer.30
Kallen et al. even reported a reduced risk of most types
of cancers, with the exception of lung cancer and endocrine cancer.31 The results from many similar reports
also connect the inflammatory process to the cancers of
the ovary, pancreas, bladder, skin, and esophagus.20
It is possible that NPC shares the common
inflammatory-induced carcinogenic mechanisms related
to the granulocyte secretions. Huang et al. found that the
tissue and serum levels of 8-Oxo-20 -deoxyguanosine, an
oxidative stress product, are significantly higher in NPC
patients compared to control patients.32 Recently Zhang
et al. also showed that EBV-infected immortalized nasopharyngeal epithelial cells often acquire an enhanced
response to interleukin (IL)26induced signal transducer
and activator of transcription 3 (STAT3) activation to promote their growth and invasive properties.33 This
enhanced IL-6/STAT3 response was mediated by overexpression of IL-6 receptor, which implies that besides the
genotoxic burden generated by the granulocyte activity, a
cytokine-receptormediated mechanism might also be
involved in the relation between inflammation and NPC.
Moreover, the IL-6mediated Janus kinase/STAT3 pathways were also shown to be involved in the hypermethylation of several tumor suppressor genes in NPC cells.34
There is even evidence that NPC cells may play a

significant role in maintaining and amplifying the inflammation process, which recruit and activate additional
immune cells in the nasopharyngeal path and promote
tumor progression.35
IL-6 is known to be an important proinflammatory
cytokine and to be expressed during the rhinosinusitis
process.36,37 It has already been shown that oxidative
stress and antioxidant enzyme activity significantly
increases during acute rhinosinusitis.38,39 In a recent
study, researchers found that the genes involved in
nitric oxide and reactive oxygen species regulation in
patients with chronic rhinosinusitis are altered.40 Evidence from all of these studies provides certain explanations to our findings that patients with rhinosinusitis
are more likely to develop nasopharyngeal carcinoma.
The major limitation of this study, like much of the
health insurance database analysis research, is the possibility of surveillance bias. This means that it is possible the patients with rhinosinusitis visit doctors more
often. In cases with chronic rhinosinusitis, patients were
more likely to receive examinations such as computed
tomography or nasal endoscopy. Therefore, it is possible
that NPC patients with underlying rhinosinusitis have a
higher chance of it being detected, whereas those in the
control group might remain symptomless and undetected
for a certain period of time. In the last part of our study,
we conducted a sensitivity analysis in which subjects
who were newly diagnosed with chronic rhinosinusitis,

TABLE III.
Crude and Adjusted Odds Ratios of Prior Acute Rhinosinusitis Between Nasopharyngeal Carcinoma Subjects and Controls (n 5 8968).
Total Sample, n 5 8,968
Presence of Prior Acute
Rhinosinusitis

No.

Yes
No

4,037
4,931

45.02
54.98

Nasopharyngeal Carcinoma
Subjects, n 5 2,242
No.

1,199
1,043

53.48
46.52

Controls, n 5 6,726
No.

2,838
3,888

42.19
57.81

Crude OR (95% CI)

1.60 (1.45-1.76)*

1.00

Adjusted OR (95% CI)

1.57 (1.43-1.73)*

1.00

*P <.001.

Conditional logistic regression conditioned on subjects age and sex, adjusted for monthly income, geographic region, urbanization level, alcohol
abuse/alcohol dependence syndrome, and tobacco use disorder.
CI 5 confidence interval; OR 5 odds ratio.

Laryngoscope 124: July 2014

1518

Hung et al.: Sinusitis and Nasopharyngeal Carcinoma

TABLE IV.
Sensitivity Analysis.
Excluding Subjects Who Received a Chronic Rhinosinusitis Diagnosis Within 1 Year Prior to the Index Date

Presence of Prior Chronic

Rhinosinusitis

Nasopharyngeal Carcinoma
Subjects, n 5 2,197
No.

Controls, n 5 6,679

No.

Yes

277

12.61

238

3.56

No

1,920

87.39

6,441

96.44

Crude OR (95% CI)

Adjusted OR (95% CI)

3.94 (3.28-4.72)*
3.90 (3.26-4.68)*

1.00
1.00

*P <.001.

Conditional logistic regression conditioned on subjects age and sex, adjusted for monthly income, geographic region, urbanization level, alcohol
abuse/alcohol dependence syndrome, and tobacco use disorder.
CI 5 confidence interval; OR 5 odds ratio.

within 1 year prior to the index date, were excluded.

This was an attempt to reduce the surveillance bias. The
OR of prior chronic rhinosinusitis for subjects with nasopharyngeal carcinoma remained significantly higher
than that of controls. The results support our original
hypothesis and reduce the chance that the increased
diagnoses of NPC resulted from accidental findings during examinations for rhinosinusitis.
The second limitation is the lack of treatment information for the rhinosinusitis group. In this database
study it is difficult to evaluate how well these patients
were treated. Therefore, there may have been some
patients who had been adequately treated for their rhinosinusitis but were still included in the rhinosinusitis
group. This could potentially affect the accuracy of data
interpretation. However, we believe this potential bias
has little effect on our conclusions. If there was a large
number of treated rhinosinusitis subjects included in the
rhinosinusitis case group, theoretically the results would
be affected toward the null hypothesis. Because the
results of our study reached statistically significant differences, we believe this limitation remain fairly
negligible.
Third, the determination of the time period of the
diagnosis of rhinosinusitis before developing NPC is
especially difficult and controversial. In this study, the
cases only included patients who had ever received a
rhinosinusitis diagnosis within 3 years prior to the index
date. This selection was intended to exclude patients
with a very long interval between the diagnosis of rhinosinusitis and the development of NPC. However, the
duration of time required for a nasal infection/inflammation to reasonably result in a carcinogenic effect remains
unknown. It is possible that under our duration selection
criteria (interval between the diagnoses of rhinosinusitis
prior to the diagnoses of NPC: <3 years for acute rhinosinusitis, <3 years and between 1 and 3 years for
chronic rhinosinusitis), we might have excluded those
who were affected by rhinosinusitis for many years and
had the highest inflammatory tissue burden. We may
have also included patients with only a short period of
rhinosinusitis, which might not have been long enough
Laryngoscope 124: July 2014

to result in carcinogenesis. Nevertheless, even under

these considerations, the results of our study remained
statistically significant.
Last, some factors such as tobacco use, alcohol and
betel quid consumption, dietary habits, body mass index,
positive family history, and elevated EBV serology,
which may have had an effect on the associations
detected in this study, were not available in the administrative dataset.

CONCLUSION
This study demonstrated an association between
rhinosinusitis and NPC. We recommend physicians to be
more aggressive when dealing with rhinosinusitis, as
this common and frequently overlooked condition may
potentially contribute to more problems than what are
conventionally expected. In addition, although the true
relationship between rhinosinusitis and NPC requires
further investigation, we recommend that patients found
to have rhinosinusitis, either acute or chronic, to seek
aggressive management to reduce both the tissue burden
and the risk of subsequently developing NPC.

BIBLIOGRAPHY
1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates
of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer
2010;127:28932917.
2. Gleeson MJ, Browning G, Burton Martin J, et al. Scott-Browns Otolaryngology. Boca Raton, FL: CRC Press, 2008.
3. Taiwan Cancer Registry Database 2009. Available at: http://cph.ntu.edu.
tw/main.php?Page5N2#. Accessed on December 12, 2013.
4. Jia WH, Qin HD. Non-viral environmental risk factors for nasopharyngeal
carcinoma: a systematic review. Semin Cancer Biol 2012;22:117126.
5. Yuan JM, Wang XL, Xiang YB, Gao YT, Ross RK, Yu MC. Preserved foods
in relation to risk of nasopharyngeal carcinoma in Shanghai, China. Int
J Cancer 2000;85:358363.
6. Farrow DC, Vaughan TL, Berwick M, Lynch CF, Swanson GM, Lyon JL.
Diet and nasopharyngeal cancer in a low-risk population. Int J Cancer
1998;78:675679.
7. Liebowitz D. Nasopharyngeal carcinoma: the Epstein-Barr virus association. Semin Oncol 1994;21:376381.
8. Hildesheim A, West S, DeVeyra E, et al. Herbal medicine use, EpsteinBarr virus, and risk of nasopharyngeal carcinoma. Cancer Res 1992;52:
30483051.
9. Gallicchio L, Matanoski G, Tao XG, et al. Adulthood consumption of preserved and nonpreserved vegetables and the risk of nasopharyngeal carcinoma: a systematic review. Int J Cancer 2006;119:11251135.

Hung et al.: Sinusitis and Nasopharyngeal Carcinoma

1519

10. Hsu WL, Chen JY, Chien YC, et al. Independent effect of EBV and cigarette smoking on nasopharyngeal carcinoma: a 20-year follow-up study
on 9,622 males without family history in Taiwan. Cancer Epidemiol Biomarkers Prev 2009;18:12181226.
11. Ung A, Chen CJ, Levine PH, et al. Familial and sporadic cases of nasopharyngeal carcinoma in Taiwan. Anticancer Res 1999;19:661665.
12. Polesel J, Franceschi S, Talamini R, et al. Tobacco smoking, alcohol drinking, and the risk of different histological types of nasopharyngeal cancer
in a low-risk population. Oral Oncol 2011;47:541545.
13. Chen L, Gallicchio L, Boyd-Lindsley K, et al. Alcohol consumption and the
risk of nasopharyngeal carcinoma: a systematic review. Nutr Cancer
2009;61:115.
14. Cheng YJ, Hildesheim A, Hsu MM, et al. Cigarette smoking, alcohol consumption and risk of nasopharyngeal carcinoma in Taiwan. Cancer
Causes Control 1999;10:201207.
15. Feng BJ, Khyatti M, Ben-Ayoub W, et al. Cannabis, tobacco and domestic
fumes intake are associated with nasopharyngeal carcinoma in North
Africa. Br J Cancer 2009;101:12071212.
16. Anon JB. Upper respiratory infections. Am J Med 2010;123:S16S25.
17. Scadding GK, Durham SR, Mirakian R, et al. BSACI guidelines for the
management of rhinosinusitis and nasal polyposis. Clin Exp Allergy
2008;38:260275.
18. Rosenfeld RM, Andes D, Bhattacharyya N, et al. Clinical practice guideline: adult sinusitis. Otolaryngol Head Neck Surg 2007;137:S1S31.
19. Yuan JM, Wang XL, Xiang YB, Gao YT, Ross RK, Yu MC. Non-dietary
risk factors for nasopharyngeal carcinoma in Shanghai, China. Int J
Cancer 2000;85:364369.
20. Fitzpatrick FA. Inflammation, carcinogenesis and cancer. Int Immunopharmacol 2001;1:16511667.
21. De Marzo AM, Platz EA, Sutcliffe S, et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer 2007;7:256269.
22. Kang JH, Chen YH, Lin HC. Comorbidity profiles among patients with
ankylosing spondylitis: a nationwide population-based study. Ann
Rheum Dis 2010;69:11651168.
23. Cheng CL, Kao YH, Lin SJ, Lee CH, Lai ML. Validation of the National
Health Insurance Research Database with ischemic stroke cases in Taiwan. Pharmacoepidemiol Drug Saf 2011;20:236242.
24. Chen YC, Yeh HY, Wu JC, Haschler I, Chen TJ, Wetter T. Taiwans
National Health Insurance Research Database: administrative health
care database as study object in bibliometrics. Scientometrics 2011;86:
365380.
25. Chang ET, Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev 2006;15:17651777.

Laryngoscope 124: July 2014

1520

26. Atula S, Auvinen E, Grenman R, Syrjanen S. Human papillomavirus and

Epstein-Barr virus in epithelial carcinomas of the head and neck region.
Anticancer Res 1997;17:44274433.
27. Zeng Y, Zhong JM, Ye SQ, et al. Screening of Epstein-Barr virus early
antigen expression inducers from Chinese medicinal herbs and plants.
Biomed Environ Sci 1994;7:5055.
28. Ekbom A, Helmick C, Zack M, Adami HO. Ulcerative colitis and colorectal
cancer. A population-based study. N Engl J Med 1990;323:12281233.
29. Ekbom A, Helmick CG, Zack M, Holmberg L, Adami HO. Survival and
causes of death in patients with inflammatory bowel disease: a
population-based study. Gastroenterology 1992;103:954960.
30. Vesterinen E, Pukkala E, Timonen T, Aromaa A. Cancer incidence among
78,000 asthmatic patients. Int J Epidemiol 1993;22:976982.
31. Kallen B, Gunnarskog J, Conradson TB. Cancer risk in asthmatic subjects
selected from hospital discharge registry. Eur Respir J 1993;6:694697.
32. Huang YJ, Zhang BB, Ma N, Murata M, Tang AZ, Huang GW. Nitrative
and oxidative DNA damage as potential survival biomarkers for nasopharyngeal carcinoma. Med Oncol 2011;28:377384.
33. Zhang G, Tsang CM, Deng W, et al. Enhanced IL-6/IL-6R signaling promotes growth and malignant properties in EBV-infected premalignant
and cancerous nasopharyngeal epithelial cells. PloS One 2013;8:e62284.
34. Murata M, Thanan R, Ma N, Kawanishi S. Role of nitrative and oxidative
DNA damage in inflammation-related carcinogenesis. J Biomed Biotechnol 2012;2012:623019.
35. Liao Q, Guo X, Li X, et al. Analysis of the contribution of nasopharyngeal
epithelial cancer cells to the induction of a local inflammatory response.
J Cancer Res Clin Oncol 2012;138:5764.
36. Ba L, Zhang N, Meng J, et al. The association between bacterial colonization and inflammatory pattern in Chinese chronic rhinosinusitis
patients with nasal polyps. Allergy 2011;66:12961303.
37. Sachse F, Becker K, von Eiff C, Metze D, Rudack C. Staphylococcus aureus invades the epithelium in nasal polyposis and induces IL-6 in nasal
epithelial cells in vitro. Allergy 2010;65:14301437.
38. Uslu C, Taysi S, Bakan N. Lipid peroxidation and antioxidant enzyme
activities in experimental maxillary sinusitis. Ann Clin Lab Sci 2003;33:
1822.
39. Braskett M, Riedl MA. Novel antioxidant approaches to the treatment of
upper airway inflammation. Curr Opin Allergy Clin Immunol 2010;10:
3441.
40. Jardeleza C, Jones D, Baker L, et al. Gene expression differences in nitric
oxide and reactive oxygen species regulation point to an altered innate
immune response in chronic rhinosinusitis. Int Forum Allergy Rhinol
2013;3:193198.

Hung et al.: Sinusitis and Nasopharyngeal Carcinoma

Copyright of Laryngoscope is the property of Wiley-Blackwell and its content may not be
copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.