Aim. This study aims to investigate the possible role of H. pylori as a cause of laryngeal squamous cell carcinoma. Method. This controlled study was performed with 31 consecutive laryngeal cancer and 28 cancer-free patients who underwent direct laryngoscopy and biopsy of laryngeal lesions. To document the previous H. pylori infection, serological analysis of the antibody titers was done. Immunohistochemical analyses were applied to the tissue samples. Results. Serology was found positive at the 90.3% of the laryngeal cancer patients and 96.4% of the benign group. There were no statistically significant differences between the two groups ( &gt; 0.05). Immunohistochemical analysis results were determined as negative at all of the specimens of laryngeal cancer patients and patients with benign lesions. Conclusion. There were no signs of colonization of H. pylori in laryngeal tissues of both groups&apos; patients. It is thought that no relationship exists between the H. pylori infection and laryngeal squamous cell carcinoma

Alperen Vural

Emdat Yüce

Ercihan Güney

Hacj Okuducu

Ragan Genç

Sedat Çallj

Tahir Patjrollu

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Hindawi Publishing Corporation
Disease Markers
Volume 35 (2013), Issue 5, Pages 447–449
http://dx.doi.org/10.1155/2013/950701
Clinical Study
The Role of H. pylori in the Development of Laryngeal
Squamous Cell Carcinoma
RaGan Genç,1 Sedat ÇaLlJ,2 Emdat Yüce,2 Alperen Vural,3 HacJ Okuducu,4
Tahir PatJroLlu,5 and Ercihan Güney2
1 Department of Otorhinolaryngology, Niğde State Hospital, Nigde Devlet Hastanesi, KBB Klinigi, 51000 Nigde, Turkey
2Department of Otorhinolaryngology, Erciyes University, Erciyes Unv. KBB Klinigi, 38039 Kayseri, Turkey
3 Department of Otorhinolaryngology, Uzunkopru State Hospital, Uzunkopru Devlet Hastanesi KBB Klinigi, 22300 Edirne, Turkey
4Department of Otorhinolaryngology, Sorgun State Hospital, Sorgun Devlet Hastanesi, KBB Klinigi, 66700 Yozgat, Turkey
5 Department of Pathology, Erciyes University, Erciyes Unv. Patoloji Bolumu, 38039 Kayseri, Turkey
Correspondence should be addressed to Alperen Vural; alperenvural@yahoo.com
Received 9 June 2013; Accepted 17 September 2013
Academic Editor: Gunter Haroske
Copyright © 2013 Raşan Genç et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Aim. This study aims to investigate the possible role of H. pylori as a cause of laryngeal squamous cell carcinoma. Method.
This controlled study was performed with 31 consecutive laryngeal cancer and 28 cancer-free patients who underwent direct
laryngoscopy and biopsy of laryngeal lesions. To document the previous H. pylori infection, serological analysis of the antibody
titers was done. Immunohistochemical analyses were applied to the tissue samples.Results. Serology was found positive at the 90.3%
of the laryngeal cancer patients and 96.4% of the benign group. There were no statistically significant differences between the two
groups (𝑃 > 0.05). Immunohistochemical analysis results were determined as negative at all of the specimens of laryngeal cancer
patients and patients with benign lesions. Conclusion. There were no signs of colonization of H. pylori in laryngeal tissues of both
groups’ patients. It is thought that no relationship exists between the H. pylori infection and laryngeal squamous cell carcinoma.
1. Introduction
Laryngeal squamous cell carcinoma (LSCC) is one of the
common cancers of the upper aerodigestive system. It
accounts for 25% of all the cancers of head and neck and
2-3% of the cancers of the whole body [1]. Tobacco is the
most important risk factor for the LSCC. The other risk
factors might be some viruses, bacteria, diet type, radiation
exposure, gastroesophageal reflux, occupation, and genetical
inheritance [2].
H. pylori, a helical shaped gram-negative microaerobic
bacterium which was described as a type 1 carcinogen by
the International Agency for Research on Cancer Working
Group (IARC-1994), is related to gastric cancer and MALT
lymphoma [3, 4]. H. pylori has also been shown in the oral
cavity, dental plaques, and saliva [5].The existence ofH. pylori
in the oral cavity and stomach can indicate the colonization
of the bacteria in the laryngeal mucosa. It is suggested that
H. pylori might play a role in the development of laryngeal
cancer by forming chronical inflammation and raising the
exposure to the carcinogens by destroying mucosal and
immune barriers.
There are several studies investigating the relationship
between H. pylori and laryngeal cancer, the results of which
still show conflict about the subject [6–12]. The aim of the
present study is to investigate the existence of H. pylori in
the laryngeal specimens of the patients with the diagnosis
of LSCC and to make a comparison with the patients with
benign larynx pathologies.
2. Patients and Method
A total of 59 patients with laryngeal pathologies were enrolled
in the study.The laryngoscopic biopsies of 31 patients revealed
the result of LSCC. Twenty eight patients had benign larynx
pathologies such as polyps or nodules. Patients with a history
of using medical treatment in terms of the eradication of H.
pylori were excluded from the study.
448 Disease Markers
Table 1:The comparison of the variables between themalignant and
benign groups.
Laryngeal pathology
𝑃Malignant (𝑛 = 31) Benign (𝑛 = 28)
𝑛 (%) 𝑛 (%)
Serology, 𝑛 (%)
Positive 28 (90.3) 27 (96.4) 0.614
Negative 3 (9.7) 1 (3.6)
Immunohistochemistry 0
H. pylori IgG antibody titers were measured from
the serum samples of the patients via Enzyme-Linked
Immunosorbent Assay (ELISA) test in order to display a
previous infection. Euroimmun (Luebeck/Germany) study
kit was used, and levels more than 20U/mL were accepted
as seropositive.
The existence ofH. pylori antigens in the specimens of all
patients was investigated with immunohistochemical stain-
ing, which was applied with streptavidin biotin peroxidase
(Str. ABC/HRP) method. As a control, biopsy specimens
taken from the antral mucosa of a patient who had H. pylori
gastritis were stained with the same method and observed in
light microscope, and the existence ofH. pylori was detected.
The results were analyzed with SPSS 15.0. Pearson chi-
square analyses were made for the comparison of the cat-
egorical variables and Student’s 𝑡-test for the numerical
variables. The normal distribution of the data was analyzed
with Shapiro-Wilk test. To determine the risk factors for
malignancy single and multiple regression analysis were
made. 𝑃 < 0.05 value was accepted as statistically significant.
3. Findings
Themean age of the patients enrolled was 50.6±10.4 (27–70).
Thirty one (52.5%) patients had malignant, and 28 (47.5%)
had benign larynx pathologies. Forty five (76.3%) of the
patients with LSCC had a history of smoking. IgG antibody
was positive in 90.3% of the patients with LSCC and 96.4% of
the ones with benign pathologies. There were no statistically
significant differences between the two groups (𝑃 > 0.05) in
terms of the results of serology. None of the slides of both
laryngeal cancer and benign laryngeal lesions revealed H.
pylori existence histochemically (Table 1).
4. Discussion
Laryngeal squamous cell carcinoma is one of the most
common cancers of the upper aerodigestive system. Tobacco
appears as the major risk factor. The other risk factors
are, alcohol, chemical carcinogens, vocal abuse, positive
family history of cancer, previous radiation exposure of
the head and neck, and human papilloma virus (HPV).
HPV is considered as a causative agent which is shown to
increase proliferation in laryngeal epithelial cells. Epithelial
cell proliferation could also be caused by other infectious
agents. H. pylori, a gram negative spiral, flagellated bacillus,
has been reported as infectious bacteria of various areas of
the stomach and duodenum and major causative agent of
various gastric diseases [13, 14]. This bacterial infection has
prevalence of about 30% in developed countries and up to
90% in underdeveloped countries [15]. H. pylori infection
is identified as an important risk factor for gastric cancer
[16, 17]. In 1994, the International Agency for Research on
Cancer and the World Health Organization classified the H.
pylori infection as a group I carcinogen [18].
Although its role is well documented in gastric cancer,
little is known about the possible association of H. pylori
infection with other carcinomas. Nowadays dental plaques,
oral lesions, saliva, and adenotonsillar tissue are considered
as reservoir of H. pylori as well as stomach. Besides, the
colonization of the H. pylori in the upper aerodigestive tract
may be facilitated by oral route or gastric oral route (Gas-
troesophageal reflux) and there might be positive association
between H. pylori infection and head and neck cancer.
H. pylori is considered to cause epithelial cell proliferation
in the laryngeal mucosa just like it does in gastric mucosa,
which eventually leads to laryngeal carcinoma [6]. Several
studies have been attempted to investigate the relationship
between H. pylori infection and laryngeal cancer. Whereas
some of these studies suggested an increased susceptibility
to laryngeal cancer, the others failed to show a positive
association. Serological studies performed to investigate the
relationship betweenH. pylori infection and laryngeal cancer
show conflicting results [7, 9, 11]. Essentially, these studies
reflect the previous H. pylori infection, and serological posi-
tivitymay be caused by the colonization of the gastricmucosa.
Tests to confirm the presence of H. pylori can be divided
into two categories: those that rely on indirect methods to
detect infection such as serology and breath urease testing
and those that are named as direct methods require invasive
interventions such as endoscopy and biopsy. Direct methods
include histopathology, culture, and rapid urease test. Each
test has its own strengths and weaknesses.
Serological tests can accurately reflect the presence or
absence of H. pylori infection, and they do not indicate
colonization of the bacteria in laryngeal tissues. The best way
to know whether the laryngeal tissues are involved by H.
pylori is to show bacterial presence in tissue. However there
are few studies that have run histological investigation of H.
pylori in laryngeal tissues [8, 10].
The first study investigating the presence of H. pylori in
laryngeal tissue was performed by Borkowski et al. [8]. In this
study, laryngeal biopsy specimens of 35 patients with chronic
laryngitis were analyzed to investigate the presence of H.
pylori by using a rapid urease test. The test was positive in six
of 35 patients (17.1%). Rapid urease test positivity in laryngeal
tissue without other evidence of H. pylori infection is not
meaningful from the standpoint of colonization. Laryngeal
tissue can be colonized by other microbiological agents
containing urease enzyme [6].
Kizilay at al. [10] refused the presence of H. pylori in
specimens fromboth cases with LSCC and patients with non-
neoplastic diseases of the larynx by using light microscope.
Specimens of both tumor and control groups were stained
with hematoxylin-eosin and modified Giemsa stains.
Disease Markers 449
Several attempts have been made for an accurate detec-
tion of H. pylori in histological sections of various tissues.
Immunostaining with monoclonal and polyclonal antibodies
has been reported as a sensitive and specific method for
identifying H. pylori [19, 20]. Akbayir et al. [6] investigated
H. pylori in specimens from 50 patients with LSCC and in 50
patients with benign laryngeal pathologies using histopatho-
logical and immunohistochemical methods. H. pylori was
identified in 28 LSCC patients under light microscopy.
However, immunohistochemical evaluation of the samples
failed to provide H. pylori-specific staining. They stated that
the absence ofH. pylori in laryngeal carcinoma tissue suggests
lack of its role in the development of laryngeal squamous cell
carcinoma and absence in benign laryngeal tissue suggests
lack of H. pylori colonization in the larynx.
In the present study, it was found that patients with LSCC
were no more likely than patients with benign lesions to have
H. pylori infection. Although there is a high incidence of
serological evidence of H. pylori infection in both groups
of patients, we could not identify H. pylori in any of biopsy
samples immunohistochemically. Taken together, the current
data suggest that the larynx is not a reservoir for colonization
of H. pylori, and H. pylori does not play a role in the
pathogenesis of laryngeal neoplasia.
Acknowledgments
This studywas approved by the Local Ethical Committee with
the registration number of 2010/72.This study was funded by
Erciyes University Scientific Research Projects Department
with the number of TSU - 10 - 2899. The authors declare that
they have no conflict of interests.
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Clinical Study The Role of H. pylori in the Development of Laryngeal Squamous Cell Carcinoma

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Clinical Study The Role of H. pylori in the Development of Laryngeal Squamous Cell Carcinoma

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