Objective: To investigate the possible role of Helicobacter pylori as a cause of squamous cell carcinoma of larynx

in a case-control study in an otolaryngology ward at an academic university. Subjects and Methods: A total of

65 patients with laryngeal cancer and 65 matched cancer-free controls underwent esophagogastroduodenoscopy

and biopsy of antral and body regions of the stomach for evaluation of Helicobacter pylori infection. Results:The

proportion of subjects with a positive rapid urease test for gastric infection was similar between the two groups

(49.2 % in cases vs. 40% in controls). However, a positive rapid urease test for body was less frequently seen in

patients with laryngeal cancer whereas a positive rapid urease test for antrum was significantly higher (P=0.04).

Conclusion: Our study failed to show Helicobacter pylori as one of the etiologies of laryngeal cancer. However, it

supported the hypothesis that colonization of Helicobacter pylori only in the gastric body might have a protective

effect against laryngeal cancer with decreasing gastric acid while antral Helicobacter pylori, increasing gastric

acid due to G cell hyperplasia, may be a predisposing factor for laryngeal cancer, with acid reflux as a possible

underlying etiology.

Keywords: Helicobacter pylori - laryngeal cancer - rapid urease test - gastric acid - esophagogastroduodenoscop

خوشباطن, منوچهر

دوست محمدیان, ثریا

دوست محمدیان, نجمه

پیرزاده, اکبر

English

ArUMS Digital Repository (سامانه اطلاعات زیست پزشکی و سلامت)

Asian Pacific Journal of Cancer Prevention, Vol 12, 2011 897
Is there any Association between Helicobacter Pylori Infection and Laryngeal Carcinoma?
Asian Pacific J Cancer Prev, 12, 897-900
Introduction
 Cancer of the larynx is the second most common 
malignancy of the upper aerodigestive tract, 85% to 95% 
of laryngeal malignancies are squamous cell carcinoma 
(SCC). Tobacco and alcohol use are the two primary risk 
factors for cancer of the larynx. Other risk factors include 
human papilloma virus (HPV), chemical carcinogens, 
positive family history for malignancy, previous 
radiotherapy and personal history of head and neck 
cancer (Flint et al., 2010).Although the relationship is not 
proven, acid pepsin diseases is regarded as a risk factor for 
laryngeal carcinoma (Doustmohammadian et al., 2010). 
HPV is epidemiologically considered as an etiologic 
factor for laryngeal cancer since it is shown to increase 
the proliferation of laryngeal epithelial cells (Jacob et al., 
2002). Other infectious agents as Helicobacter pylori (HP) 
might also cause epithelial cell proliferation and cancer. 
 The prevalence of HP varies throughout the world 
and depends largely on the overall standard of living in 
the region. In developing parts of the world, 80% of the 
population may be infected by the age of 20, whereas the 
prevalence is 20-50% in industrialized countries (Fauci 
et al., 2008).
1Otorhinolaryngology Dept, Ardebil University of Medical Sciences, Ardebil, 2Otorhinolaryngology Dept, Semnan University 
of Medical Sciences, Semnan, 3Gastroenterology and Hepatology Dept, Tabriz University of Medical Sciences, Tabriz, 4Internal 
Medicine, Tehran University of Medical Sciences, Tehran, Iran *For correspondence: n_dostmohammadian@yahoo.com
Abstract
 Objective: To investigate the possible role of Helicobacter pylori as a cause of squamous cell carcinoma of larynx 
in a case-control study in an otolaryngology ward at an academic university. Subjects and Methods: A total of 
65 patients with laryngeal cancer and 65 matched cancer-free controls underwent esophagogastroduodenoscopy 
and biopsy of antral and body regions of the stomach for evaluation of Helicobacter pylori infection. Results:The 
proportion of subjects with a positive rapid urease test for gastric infection was similar between the two groups 
(49.2 % in cases vs. 40% in controls). However, a positive rapid urease test for body was less frequently seen in 
patients with laryngeal cancer whereas a positive rapid urease test for antrum was significantly higher (P=0.04). 
Conclusion: Our study failed to show Helicobacter pylori as one of the etiologies of laryngeal cancer. However, it 
supported the hypothesis that colonization of Helicobacter pylori only in the gastric body might have a protective 
effect against laryngeal cancer with decreasing gastric acid while antral Helicobacter pylori, increasing gastric 
acid due to G cell hyperplasia, may be a predisposing factor for laryngeal cancer, with acid reflux as a possible 
underlying etiology.
Keywords: Helicobacter pylori - laryngeal cancer - rapid urease test - gastric acid - esophagogastroduodenoscopy
RESEARCH COMMUNICATION
Is there any Association between Helicobacter Pylori Infection 
and Laryngeal Carcinoma?
Akbar Pirzadeh1, Najmeh Doustmohammadian&2*, Manochehr Khoshbaten3, 
Sorayya Doustmohammadion4
 HP is a gram – negative spiral bacterium known to be 
one of the most virulent bacteria worldwide. It usually 
causes chronic bacterial infection in humans and has been 
associated with gastritis, peptic ulcer, gastric cancer and 
other gastrointestinal disorders (Wang et al., 2007; Fauci 
et al., 2008).
 HP colonization induces a tissue response in the 
stomach termed chronic superficial gastritis(Fauci et 
al., 2008). Antral – predominant gastritis is most closely 
linked with duodenal ulceration,while gastric ulceration 
and adenocarcinoma arise in association with pan or corpus 
– predominant gastritis. The inflamed acid – producing 
gastric corpus produces less acid with consequent 
relative hypochlorhydria despite hypergastrinomia (Fauci 
et al.,2008).Much attention has been focused on the 
possible protective role of HP against Gastroesophageal 
Reflux Disease (GERD). The mechanism underlying 
this protective effect appears to include HP– induced 
hypochlorhydria (Fauci et al., 2008).Therefore, it could 
be postulated that HP of gastric corpus, decreasing gastric 
acid, is protective against GERD and laryngeal cancer. 
HP of antrum, increasing gastric acid, plays a role in the 
pathogenesis of laryngeal cancer.
 HP infection is diagnosed by either invasive (endoscopy 
Akbar Pirzadeh et al
Asian Pacific Journal of Cancer Prevention, Vol 12, 2011898
and biopsy)or non-invasive (urease breath test (UBT), 
serology, and stool antigen testing) techniques. invasive 
test, which require upper gastrointestinal endoscopy and 
are based on the analysis of gastric biopsy specimens. If 
endoscopy is performed, the most convenient biopsy – 
based test is the Urease Test in which biopsy specimens 
are placed into a gel containing urea and an indicator. The 
presence of HP, urease elicits a color change which often 
occurs within minutes but can require up to 24h (Fauci et 
al.,2008). 
 Several studies have been performed to evaluate the 
association between HP and laryngeal cancer. Some 
studies have shown that HP is as an etiologic factor 
for laryngeal carcinoma and some other studies have 
investigated the protective effect of HP against laryngeal 
cancer (Aygene et al., 2001; Zhuo et al., 2003; Akbayir et 
al., 2005; Nurgalieva et al., 2005; Fang et al., 2008;Titiz 
et al., 2008; Masoud et al.,2008).
  None of the published studies compared the existence 
of HP in two separate parts of the stomach - corpus and 
antrum - in patients with laryngeal carcinoma and in 
cancer-free controls.
 
Materials and Methods
 This study was approved by ethics committee of Liver 
and Gastrointestinal Disease Research Center, Tabriz 
university of Medical Sciences. Study procedures were 
explained by a designated research assistant and written 
information was also given. Informed written consent was 
obtained from each patient who wished to participate. 
Totally, 65 patients who had undergone laryngoscopy 
and biopsy with the definite diagnosis of squamous cell 
carcinoma as well as those who had undergone total or 
partial laryngectomy between May 2006 and February 
2008 at academic hospitals affiliated to Tabriz University 
of Medical Sciences were evaluated. These patients 
underwent esophagogastroduodenoscopy (EGD) and 
biopsy of the antrum and body of the stomach. Tissue 
specimens from 2-3 cm above the pylorus and 2-3 cm 
below the cardia with separate two forceps were placed 
on a gel containing urea and an indicator and then color 
change was evaluated during the first hour and after 24 
hours. After 24 hours, a yellow color indicated a negative 
and an orange to red color indicated a positive result. 
 Control group (65 patients) were hospitalized patients 
with anemia or other illnesses not associated with HP. 
These patients did not have signs of laryngeal cancer in 
their medical history and laryngoscopy. These controls, 
similar to the case group, underwent EGD and biopsy 
of the stomach. A complete medical history including 
demographic data such as age and sex, medical history, 
history of cigarette smoking and alcohol was obtained 
from each patient.
 Patients who had used antibiotics, antiacid drugs 
or proton – pump inhibitors for peptic ulcer during the 
previous 2-4 weeks were excluded from this study. Tissue 
specimens from laryngeal cancer (65 patients) and benign 
laryngeal lesions (40 patients) were also investigated for 
the existence of HP with histopathologic evaluation and 
rapid urease test.
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 Clinical characteristics and laboratory variables were 
compared by Independent sample T-test, c2 test and 
Fisher exact test. A p-value less than 0.05 was considered 
statistically significant. All analyses were performed using 
the Statistical Package for the Social Science Software 
(SPSS).
Results 
 Our case group included 63 males and 2 females 
with a mean age of 61.8 ± 7.7 years. The control group 
consisted of 63 males and 2 females with a mean age of 
61.7 ± 7.6 years. In the population with laryngeal cancer, 
the prevalence of smoking and alcohol consumption was 
78.5 % and 29.2%, respectively. In the control group, they 
were 73.8 % and 26.2 %, respectively. The characteristics 
of the case and the control group are presented in Table 
1. The cases and controls were matched in terms of 
age, sex, amount and duration of tobacco and alcohol 
consumption and did not have any significant differences. 
The proportion of subjects with a positive rapid urease test 
(RUT) for gastric HP was similar between the two groups 
[32 (49.2 %) in cases vs. 26 (40 %) in controls, p=0.290]. 
However, a positive RUT for body HP was less frequently 
seen in patients with laryngeal cancer than in controls 
without laryngeal cancer and difference was statistically 
significant. (5/32 in cases vs. 10/26 in controls, p = 0.04).
A positive RUT for antrum HP was significantly higher 
in patients with laryngeal cancer than in controls and 
difference was statistically significant. (27/32 in cases 
vs. 16/26 in controls, p = 0.04). Tissue specimens from 
laryngeal cancer (65 patients) and  benign laryngeal 
lesions  (40 patients)were also investigated for the 
existence of HP with histopathologic evaluation and 
RUT. During rapid urease testing, none of the subjects 
(in either of the groups) showed color change during the 
first hour. While 65 slides of laryngeal cancer (squamous 
cell carcinoma) and 40 slides of benign laryngeal lesions 
(polyp, nodule) were stained with haematoxylin-eosin, 
none  revealed HP existence.
Discussion
Upper aerodigestive tracts have many common 
etiologies such as smoking and alcohol use. Larynx is 
a part of the upper aerodigestive tract. Therefore, since 
HP is a known etiologic factor for gastric cancer, it could 
be postulated that HP plays a role in the pathogenesis of 
laryngeal cancer. The present study found no evidence in 
support of this hypothesis.
 Prior investigators have studied HP as an etiologic 
Table 1. Characteristics of Patients with and without 
Laryngeal Cancer 
Characteristic              with            without    p-value
Mean age (Yr ± SD)     61.8 ± 7.70   61.7 ± 7.62                
Tobacco use           51  (78.5%)           48 (73.8%)             
Alcohol use                 19  (29.2%)      17 (26.2%)
RUT Body HP   5/32 (15.6%)  10/26 (38.5%)
RUT Antral HP 27/32 (84.3%) 16/26 (61.5%) 
RUT, rapid urease test positive
Asian Pacific Journal of Cancer Prevention, Vol 12, 2011 899
Is there any Association between Helicobacter Pylori Infection and Laryngeal Carcinoma?
factor for laryngeal carcinoma. Kizilay et al (2006) 
investigated 69 total laryngectomy specimens with 
squamous cell carcinoma and 30 laryngeal tissue samples 
with non-neoplastic diseases (polyp, nodule) but none 
demonstrated HP infection. However, diagnosis was 
solely on the basis of histology. Akbayir et al(2005) 
examined 50 patients with laryngeal cancer and 50 
benign laryngeal biopsy specimens by histopathological 
and immunohistochemical techniques, but again none 
demonstrated HP infection .In our study, HP was not 
detected in malignant and benign specimens of larynx 
when both rapid urease testing and pathology were applied, 
therefore, it is unlikely for HP to be colonized in larynx. 
Nevertheless, we suppose that larynx is not a permanent 
reservoir for HP. More exact researches with Polymerase 
Chain Reaction study for HP are recommended. In our 
study, a positive RUT for gastric HP was similar between 
the two groups but a positive RUT for antral HP was 
significantly different between the two groups.
Several serologic studies have been performed to 
evaluate the association between HP and laryngeal cancer. 
Aygene et al investigated the presence of IgG antibodies 
against HP antigens by ELISA technique in 26 patients 
with squamous cell carcinoma of larynx and 32 matched 
controls. They found that 73.1% of the patients with 
squamous cell carcinoma and 40.6 % of the controls were 
seropositive. (P < 0.05) (Aygene et al,2001).
Rubin et al reported that the presence of HP antibodies 
was significantly higher in patients with laryngeal 
dysplasia or frank carcinoma of the head and neck in 
comparison with their associated controls (Rubin et al., 
2003).
It should be noted that the prevalence of HP varies 
throughout the world. In developing parts of the world 
such as Iran, 80 % of the population may be infected by the 
age of 20 and therefore, serologic studies are not suitable 
for such societies. In a study from Iran, seropositivity of 
HP (ELISA) in the age range of 41-50 and 51-60 was 
73.46% and 75.75%, respectively (Jafarzadeh et al.,2007). 
Jaspersen et al(1998) investigated the association 
between HP and chronic laryngitis. Thirty six patients 
with chronic laryngitis underwent gastroscopy. Biopsies 
were taken from the gastric antrum and body and lower, 
middle and upper esophagus. HP was diagnosed through 
RUT and histology. They concluded that there was no 
evidence for the existence of HP – associated laryngitis, 
suggesting that acid reflux is the underlying etiology. 
Absence of a control group and few cases of the study 
were limitations of this study.
In our study, a positive RUT for body HP was less 
frequently seen among patients with laryngeal cancer than 
in controls and the difference was statistically significant. 
It could support the hypothesis that body HP may be 
protective against laryngeal cancer through decreasing 
gastric acid.
The only Study that has investigated the protective 
role of body HP against laryngeal cancer was performed 
by Nurgalieva et al(2005).The aim of this study was to 
investigate whether HP infection also protects against 
laryngopharyngeal carcinoma. One hundred and ninety 
case subjects and 111 control subject were included in 
the study. The proportion of subjects with anti – HP IgG 
was similar between the two groups (32.8 % in cases vs. 
27.0 % in controls, p = 0.342) but the difference was not 
statistically significant. This study had some limitations. 
First, HP of the body and antrum were not separately 
evaluated and second, the study was based on serologic 
findings.
In our study, a positive RUT for Antrum HP was higher 
in patients with laryngeal cancer than in controls and the 
difference was statistically significant. Antral HP may be 
a predisposing factor for laryngeal cancer, probably via 
increasing gastric acid, suggesting that acid reflux is the 
underlying etiology .
In conclusion, our study failed to show Helicobacter 
pylori as one of the etiologies of laryngeal cancer. 
However, a positive RUT for body HP was less frequently 
seen among patients with laryngeal cancer than in controls 
and the difference was statistically significant. It could 
support the hypothesis that body HP may be protective 
against laryngeal cancer with decreasing gastric acid. A 
positive RUT for antrum HP was higher in patients with 
laryngeal cancer than in controls and the difference was 
statistically significant. Antral HP may be a predisposing 
factor for laryngeal cancer, probably via increasing gastric 
acid due to G cell hyperplasia, suggesting that acid reflux 
may be the underlying etiology and acid suppression 
postlaryngeal cancer therapies may have protective effects 
on laryngeal cancer recurrence rates. 
In our study, a  certain  association between gastric 
acid with laryngeal cancer was not found, since no PH 
study was carried out. But HP in two separate areas of 
stomach (antrum and body)in two groups was different, 
probably HP in these two areas had different effect on 
gastric acid and laryngeal cancer. More research with PH 
study is recommended.
 
Acknowledgements 
Financial and material support for this research and 
work was received from the Liver and Gastrointestinal 
Disease Research Center, Tabriz University of Medical 
Sciences. The authors declare  no conflict of interest. 
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Is there any Association between Helicobacter Pylori Infection and Laryngeal Carcinoma

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Is there any Association between Helicobacter Pylori Infection and Laryngeal Carcinoma

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