Journal of

Oral Pathology & Medicine

doi: 10.1111/j.1600-0714.2011.01006.x

J Oral Pathol Med (2011) 40: 317324

2011 John Wiley & Sons A/S All rights reserved
wileyonlinelibrary.com/journal/jop

Helicobacter pylori in the oral cavity and gastric mucosa:

a meta-analysis
Qing-Hua Zou1, Ren-Qing Li2
1

Department of Microbiology, Peking University Health Science Center, Beijing, China; 2Beijing Center for Disease Control and
Prevention, Beijing, China

BACKGROUND: Helicobacter pylori have been found in

the oral cavity and stomach. This study is to establish
whether there might be any associations between isolates
of H. pylori in the oral cavity and those in the stomach by
meta-analysis.
METHODS: Studies reporting raw data on the prevalence of H. pylori infection in the oral cavity in gastric
H. pylori-positive and H. pylori-negative patients, in
patients with gastroesophageal diseases, and in healthy
individuals and studies reporting data on the eradication
rate in the oral cavity or stomach, published in the English language, were identified through MEDLINE and
EMBASE up to May 2010.
RESULTS: The prevalence of H. pylori infection in the
oral cavity in gastric H. pylori-positive patients was significantly higher (45.0%) than that in gastric H. pylorinegative patients (23.9%). The pooled odds ration (OR)
was 3.61 and the 95% CI was 1.916.82 (P < 0.0001). Different diagnostic methods produced different pooled ORs
with PCR the highest (OR = 5.11, 95% CI: 2.0812.54,
P = 0.0004) and rapid urease test (RUT) the lowest
(OR = 2.00, 95% CI: 0.805.00, P = 0.14). The 44.8%
(91 203) prevalence of H. pylori infection in the oral
cavity in patients with clinical and or histological gastroesophageal diseases was significantly higher than the
13.2% (21 159) in patients with non-ulcerous dyspepsia or
healthy controls (OR = 5.15, 95% CI: 2.978.92,
P < 0.00001). The eradication efficiency in stomach is
85.8% (187 218), while in oral cavity it is only 5.7%
(9 158). The OR is 55.59, P < 0.00001.
CONCLUSIONS: There is a close relation between the
infection of H. pylori in the oral cavity and stomach.
H. pylori in the oral cavity are more difficult to be eradicated than in the stomach. It may be a source of reinfection.
J Oral Pathol Med (2011) 40: 317324

Correspondence: Qing-Hua Zou, Department of Microbiology,

Peking University Health Science Center, 38 Xueyuan Road, Beijing
100191, China. Tel: 86 10 8280 2807, Fax: 86 10 8280 2807, E-mail:
zouqinghua@bjmu.edu.cn
Accepted for publication January 2, 2011

Keywords: gastric mucosa; Helicobacter pylori; meta-analysis; oral

cavity; oral mucosa; saliva

Introduction
Helicobacter pylori is a major human pathogen responsible for gastritis, gastroduodenal ulcers, and gastric
malignancies (1). It has been designated as a type I
carcinogen by World Health Organization, as it is
associated with the development of gastric adenocarcinoma, the second most commonly diagnosed fatal
cancer (2). Approximately, half of the worlds population is believed to be infected with H. pylori (3), and the
infection is signicantly more prevalent in developing
countries, where the reported prevalence in adult is
around 90% (4). As H. pylori reside in the human
stomach, knowledge of the mechanism leading to gastric
infection is crucial for the development of optimal
measures aimed at eradicating bacteria from the host
and the environment. However, to date, the exact mode
and route of transmission of the microorganism is still
unknown. Success in isolating or detecting H. pylori
DNA by PCR from dental plaque (DP) (5), saliva (6),
dorsum of the tongue (7), surface of oral ulcerations (8),
or oral neoplasia (9) drew attention to the possible
importance of oral oral transmission. Studies (1014)
have described evidence supporting the role of the oral
cavity as a reservoir for H. pylori. Occurrence of the
same strain of H. pylori in the stomach and DP has been
reported (15). Several studies showed that systemic
therapy failed to clear H. pylori from DP, despite its
clearance from the stomach (7, 16, 17). These observations suggest that oral cavity may be another niche
for H. pylori and may be the source of infection,
re-infection, and transmission. Conversely, other investigators did not nd this bacterium in the oral environment and suggest oral cavity may not be a reservoir for
H. pylori (9, 1820). To date, the association between
simultaneous colonization of H. pylori in the oral cavity
and that in stomach has not been established. Therefore,
this study was designed to elucidate the relationship

Helicobacter pylori in the oral cavity and gastric mucosa

Q.-H. Zou and R.-Q. Li

318

between the infection of H. pylori in both the oral cavity

and stomach by a meta-analysis.

Methods
Search strategy
MEDLINE (National Library of Medicine, Rockville,
MD, USA) and EMBASE (Elsevier B. V., Radarweg, the
Netherlands) searches of the English language literature
describing human studies were performed using keywords Helicobacter pylori and gastric and DP or
saliva or oral or tongue published up to April 2010.
Inclusion and exclusion criteria
Inclusion criteria were as follows: observational studies
that provide raw data dealing with H. pylori infection in
both the oral cavity and stomach, published in the
English language; H. pylori infection that had to be
conrmed by histology culture PCR urea breath test
RUT for which we took the authors denition; at least
one positive test was regarded as conrmation of infection. Exclusion criteria were as follows: studies without
raw data of H. pylori infection rate or subject numbers
for retrieval, unpublished papers, and abstracts.
Data extraction
Data were extracted by two independent reviewers
(QHZ, RQL) and agreement was reached by discussion.
Key information included the year of publication,
location of the study, types of oral specimen, test
method for oral and gastric specimens, number of oral
H. pylori-positive specimens in gastric H. pylori-positive
and H. pylori-negative patients, in patients with gastroesophageal diseases, and in patients with non-ulcerous
dyspepsia or healthy controls, number of eradicated
subjects in gastric H. pylori-positive patients and oral
H. pylori-positive patients.
Statistical analysis
Meta-analysis was performed using Cochrane software
Review Manager Version 4.2 (The Nordic Cochrane
Centre, Rigshospitalet, Denmark). Subgroup analysis
was performed to assess the factors that might impact
the pooled estimates and to investigate the source of
heterogeneity.
The primary outcome was the prevalence of H. pylori
in the oral cavity in gastric H. pylori-positive patients
compared with gastric H. pylori-negative patients. Secondary outcomes were the prevalence of H. pylori
infection in the oral cavity in patients with clinical
and or histological gastroesophageal diseases compared
with that in patients with non-ulcerous dyspepsia or
healthy controls. Tertiary outcomes were the eradication
eciency of H. pylori in stomach compared with that in
oral cavity. The proportion of patients with infection
was calculated for each group, and an odds ration (OR)
and 95% CI and the weight of the studies were
calculated for each study in a random-eects model or
in a xed-eects model. A level of signicance <0.05
was considered statistically signicant. The test for
heterogeneity was analyzed by Cochranes chi-square
J Oral Pathol Med

test. A P value of <0.10 was considered to show

signicant heterogeneity between studies. If there was a
signicant heterogeneity (P < 0.1), we selected a random-eects model to pool the data. If not, we selected a
xed-eects model to pool the data. However, because
this test would be underpowered when there are only a
limited number of studies, we further explored heterogeneity derived from another statistic method, the I2
metric, which is independent of the number of combined
studies and describes the proportion of variability across
studies that is because of genuine heterogeneity and
measures the degree of inconsistency across studies. If
I2 = 0, there is no heterogeneity. If I2 > 50%, heterogeneity is indicative. The larger is the value, the greater
is the heterogeneity.
Publication bias
Funnel plots and Beggs test were used to detect the
existence of publication bias of pooled ORs.

Results
Characters of the articles in our meta-analysis
Of 571 literature citations found by our search, 26 studies
met the inclusion criteria and were included in the
meta-analysis. Of these, 22 studies compared H. pylori
infection in the oral cavity of gastric H. pylori-positive
patients with that in gastric H. pylori-negative patients
(Table 1). Based on the methods to detect H. pylori in
the oral cavity, the studies were divided into three
groups. Group 1 used PCR methods, group 2 used RUT,
and group 3 used culture method. For group 1, we
subdivided the studies into 3 subgroups by dierent
genes for PCR. Reports from Hardo 1995 (21), Kim 2000
(22), Oshowo 1998 (23), and Suk 2002 (16) included two
dierent methods to detect H. pylori in the oral cavity. In
the 26 studies, we also found ve studies that compared
H. pylori infection in the oral cavity of patients with
clinical and or histological gastroesophageal diseases
with patients with non-ulcerous dyspepsia or healthy
controls (Table 2). Five studies compared the eradication eciency of H. pylori in stomach with that in oral
cavity (Table 3).
Prevalence of H. pylori infection in the oral cavity in
gastric H. pylori-positive patients compared with gastric
H. pylori-negative patients
When all studies, regardless of methods, were combined
in our initial analysis, there was a signicant dierence
in H. pylori infection rates in the oral cavity between
gastric H. pylori-positive and H. pylori-negative patients.
The prevalence of H. pylori infection in oral cavity was
45.0% (490 1088) for gastric H. pylori-positive patients
and 23.9% (196 821) for gastric H. pylori-negative
patients (Fig. 1). The heterogeneity chi-square statistic
was 53.37 (P < 0.0001). Therefore, the pooled estimates
were evaluated under a random-eects model instead of
a xed-eects model. The pooled OR was 3.61 and the
95% CI was 1.916.82 (P < 0.0001), suggesting that
H. pylori in oral cavity is associated with gastric
infection (Fig. 1). Subgroup analysis was performed to

Oral specimen identication methodsa

Gastric biopsy histological examination

Gastric biopsy PCR

0 34
2 116

16 44
28 38
58 65
61 65
52 63
48 48
29 29

Gastric biopsy RUT

Gastric biopsy RUT, histological examination, PCR
Gastric biopsy histological, RUT
Gastric biopsy histological, CLO test
Gastric biopsy histological examination
Gastric biopsy CLO test
Gastric biopsy CLO, Culture, histological
examination

Gastric
Gastric
Gastric
Gastric

0 21
7 24
0 23
28 38

30 40
57 68
2 29
88

Gastric biopsy culture, PCR, histological examination

Gastric biopsy culture, PCR, histological examination
Gastric biopsy CLO, culture, histological examination
- UBT
biopsy histological examination, RUT
biopsy histological examination, PCR
biopsy PCR
biopsy RUT, histological examination, PCR

0 44
0 29
0 92
2 62
10 65

4 23
1 20
15 116
12 54
6 29

0 28
0 92

14 44
27 27
49 69
7 10
12 18
30 30
16 17

1 10
58
0 27
0 27

3 16
3 17
0 17
12 12

08
07
0 28
5 17

5 13
7 18
1 34
13 28

Prevalence of
H. pylori infection
in oral cavity in
gastric
H. pylori-negative
patients (n N)

Gastric biopsy histological examination

Gastric biopsy histological examination
Gastric biopsy histological examination
Gastric biopsy culture, histological
examination, RUT, UBT
Gastric biopsy RUT
Gastric biopsy RUT
Gastric biopsy PCR
Gastric biopsy RT-PCR
Gastric biopsy culture

Gastric specimen identication methods

Prevalence of
H. pylori infection
in oral cavity in
gastric
H. pylori-positive
patients (n N)

DP, supragingival dental plaque, subgingival and supragingival plaque; UBT, urea breath test; RUT, rapid urease test; CLO test, Campylobacter-like organism test.
a
Contents in the bracket indicate the genes for PCR amplication in the studies.

Group 3: oral specimen identied by culture

Hardo (21) (UK)
DP culture
Oshowo (23) (UK)
DP, saliva, tongue, mouth,
pharynx swab culture

Group 1: oral specimen identied by PCR

Subgroup 1: PCR based on 16S rRNA
Mapstone (5) (UK)
Saliva, DP nested PCR (16S rRNA)
Nguyen (12) (USA)
DP RT-PCR (16S rRNA)
Hardo (21) (UK)
DP PCR (16S rRNA)
Umeda (14) (Japan)
DP, tongue plaque, saliva nested
PCR (16S rRNA)
Eskandari (33) (Iran)
DP PCR (16S rRNA)
Kignel (19) (Brazil)
DP PCR (16s rRNA)
Oshowo (23) (UK)
DP, saliva, tongue swabs PCR (16s rRNA)
Okuda (9) (Japan)
DP RT-PCR (16S rRNA)
Burgers (18) (Germany)
DP, saliva, tongue swabs PCR (16S rRNA)
Subgroup 2: PCR based on 860 -bp fragment
Li (11) (USA)
Saliva PCR(860- bp DNA fragment)
Li (13) (USA)
Saliva PCR (860 -bp DNA fragment)
Kim (22) (Korea)
DP, saliva PCR (860- bp DNA fragment)
Song (34) (Germany)
DP, saliva nested PCR
(860- bp DNA fragment)
Subgroup 3: PCR based on urease or cagA
Cammarota (35) (Italy)
DP PCR (urease A)
Berroteran (24) (Venezuela)
DP PCR (urease)
Sahin (27) (Turkey)
DP PCR (urea, cagA)
Suk (16) (Taiwan)
DP PCR (cagA)
Group 2: oral specimen identied by RUT
Chitsazi (36) (Iran)
DP RUT
Suk (16) (Taiwan)
DP RUT
Anand (37) (India)
DP RUT
Gurbuz (17) (Turkey)
DP CLO test
Ozdemir (7) (Turkey)
DP CLO test
Butt (10) (Pakistan)
DP CLO test
Kim (22) (Korea)
DP, saliva CLO test

Study (ref.) (country)

Table 1 Characteristics of included studies on oral Helicobacter pylori infection in gastric H. pylori-positive and H. pylori-negative patients

Helicobacter pylori in the oral cavity and gastric mucosa

Q.-H. Zou and R.-Q. Li

319

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Helicobacter pylori in the oral cavity and gastric mucosa

Q.-H. Zou and R.-Q. Li

320

Table 2 Characteristics of included studies on oral Helicobacter

pylori infection in patients with clinical and or histological gastroesophageal disease or in patients with non-ulcerous dyspepsia or
healthy controls

Study (ref.) (country)

Morales (38) (Mexico)
Umeda (14) (Japan)
Berroteran (24) (Venezuela)
Medina (39) (Argentina)
Dore-Davin (40) (USA)

Prevalence of
H. pylori infection
in the oral cavity
in casea (n N)

Prevalence of
H. pylori infection
in oral cavity in
controlb (n N)

34 66
18 45
12 32
15 43
12 17

13 65
2 12
3 20
3 55
07

a
Case include patients with clinical and or histological gastroesophageal disease, subjects exposed to H. pylori.
b
Control include patients with non-ulcerous dyspepsia or healthy
individuals, non-H. pylori-exposed subjects.

investigate the source of heterogeneity and detect the

inuential factors that could impact the summary
estimates. The methodological and biologic heterogeneity of the studies made it possible to explore the
summary estimates in dierent subgroups. The 22
studies utilized three methods, PCR, RUT, and culture,
to test for the presence of H. pylori in the oral cavity.
The pooled OR of PCR was highest (OR = 5.11, 95%
CI: 2.0812.54, P = 0.0004), and the pooled OR of
RUT was lowest (OR = 2.00, 95% CI: 0.805.00,
P = 0.14) (Fig. 1). Heterogeneity can be seen in the
two methods. Because PCR is widely used to test the
prevalence of H. pylori in oral samples and dierent
primers vary in sensitivity and specicity, we analyzed
the results based on 16S rRNA, 860-bp fragment, and
urease or cagA. Subgroup analysis revealed a signicant
dierence between the three genes. The pooled OR of
860 -bp fragment was 15.16 (95% CI: 5.8239.51,
P < 0.00001), signicantly dierent from the pooled
OR of urease or cagA of 1.71(95% CI: 0.02174.44,
P = 0.82). The pooled OR of 16S rRNA was 4.07, 95%
CI: 1.938.57, P = 0.0002. No heterogeneity was
detected in subgroup 16S rRNA and 860-bp fragment
(P = 0.30, I2 = 16.5% and P = 0.48, I2 = 0%,
respectively); however, great heterogeneity was detected
in subgroup urease or cagA (P < 0.0001, I2 = 89.7%).

The sources for heterogeneity in the studies were

analyzed. We found three studies, namely Berroteran
2002 (24), Li 1996 (13), and Suk 2002 (16), account for
the heterogeneity. When these three studies were
excluded, no heterogeneity can be seen. The total OR
is 3.35; ORs for PCR, RUT, and culture method are
4.41, 2.40, and 4.04, respectively, after excluding, which
is not signicantly dierent than the values 3.61, 5.11,
2.00, and 4.04 before excluding the studies.
Sensitivity analyses were conducted by separating
studies with factors that could have a possible impact on
heterogeneity of studies, including dierent H. pylori
detection methods in oral cavity and gastric biopsies,
dierent publication years (studies before year 2000 vs.
after year 2000), and geography (developed countries
and developing countries). The conclusion that the
prevalence of H. pylori infection in oral cavity is
signicantly higher in gastric H. pylori-positive patients
than in gastric H. pylori-negative patients remained
unchanged.
The funnel plot did not show evidence of publication
bias (Beggs test z = 1.65 [continuity corrected],
Pr > |z| = 0.098 [continuity corrected]).
Prevalence of H. pylori infection in the oral cavity in
patients with clinical and or histological gastroesophageal
diseases with patients with non-ulcerous dyspepsia or
with healthy controls
Five studies, which provided data on H. pylori infection
in oral cavity in patients with clinical and or histological
gastroesophageal diseases and in patients with nonulcerous dyspepsia or healthy controls, were included
for analysis. The 44.8% (91 203) prevalence of H. pylori
infection in the oral cavity in patients with clinical
and or histological gastroesophageal disease was significantly higher than the 13.2% (21 159) in patients with
non-ulcerous
dyspepsia
or
healthy
controls
(OR = 5.15, 95% CI: 2.978.92, P < 0.00001). No
heterogeneity was seen (P = 0.54, I2 = 0%) (Fig. 2).
Eradication eciency of H. pylori in stomach compared
with that in oral cavity
Five studies provided raw data for H. pylori eradication
eciency in stomach and oral cavity. There was

Table 3 Characteristics of included studies on the eradication efciency of Helicobacter pylori in stomach compared with that in oral cavity

Study (ref.) (country)

Oral specimen
identication
methods

Suk (16) (Taiwan)

DP, saliva PCR

(16S rRNA)
DP, saliva, tongue
PCR(16S rRNA)
DP PCR (cagA)

Gurbuz (17) (Turkey)

DP CLO test

Ozdemir (7) (Turkey)

DP CLO test

Dore-Davin (40) (USA)

Gebara (41) (Brazil)

Eradication
rate in
stomach (n N)

Eradication
rate in oral
cavity (n N)

- UBT

14 22

39

Gastric biopsy urease test, PCR

27 30

4 13

Gastric biopsy RUT, histological

examination, PCR
Gastric biopsy histological
examination, CLO test
Gastric biopsy histological
examination

32 38

2 28

54 65

0 68

60 63

0 40

Gastric specimen identication

methods

DP, dental plaque; RUT, rapid urease test; UBT, urea breath test.
J Oral Pathol Med

Helicobacter pylori in the oral cavity and gastric mucosa

Q.-H. Zou and R.-Q. Li

Review:
Comparison:
Outcome:

321

Helicobacter pylori in the oral cavity and gastric mucosa: A meta-analysis

05 Prevalence of H. pylori in the oral cavity of gastric H. pylori-positive patients and negative patients
01 Prevalence of H. pylori in the oral cavity of gastric H. pylori-positive patients and negative patients

Study
or sub-category

Gastric positive
n/N

Gastric negative
n/N

OR (random)
95% CI

Weight
%

01 PCR
7/24
5/8
Berroteran et al. 2002
6/29
10/65
Burgers et al. 2008
0/21
1/10
Cammarota et al. 1996
4/23
0/44
Eskandari et al. 2010
1/34
0/28
Hardo et al. 1995
1/20
0/29
Kignel et al. 2005
2/29
0/17
Kim et al. 2000
30/40
3/16
Li et al. 1995
57/68
3/17
Li et al. 1996
5/13
0/8
Mapstone et al. 1993
7/18
0/7
Nguyen et al. 1993
12/54
2/62
Okuda et al. 2000
15/116
0/92
Oshowo et al. 1998
0/23
0/27
Sahin et al. 2001
8/8
12/12
Song et al. 2000
28/38
0/27
Suk et al. 2002
13/28
5/17
Umeda et al. 2003
586
486
Subtotal (95% CI)
Total events: 196 (gastric positive), 41 (gastric negative)
Test for heterogeneity: c 2 = 38.91, df = 14 (P = 0.0004), I 2 = 64.0%
Test for overall effect: Z = 3.56 (P = 0.0004)
02 RUT
58/65
Anand et al. 2006
48/48
Butt et al. 2002
16/44
Chitsazi et al. 2006
61/65
Gurbuz et al. 2003
29/29
Kim et al. 2000
52/63
Ozdemir et al. 2001
28/38
Suk et al. 2002
352
Subtotal (95% CI)
Total events: 292 (gastric positive), 155 (gastric negative)
Test for heterogeneity: c 2 = 12.01, df = 5 (P = 0.03), I 2 = 58.4%
Test for overall effect: Z = 1.49 (P = 0.14)

5.53
7.03
2.64
3.03
2.69
2.68
2.87
6.15
6.26
2.93
2.98
5.87
3.23

3.15
6.60
63.65

0.25 [0.05, 1.33]

1.43 [0.47, 4.41]
0.15 [0.01, 3.96]
20.54 [1.05, 400.27]
2.55 [0.10, 65.13]
4.54 [0.18, 117.20]
3.18 [0.14, 70.27]
13.00 [3.06, 55.15]
24.18 [5.94, 98.46]
11.00 [0.52, 231.61]
9.78 [0.48, 197.85]
8.57 [1.82, 40.30]
28.25 [1.67, 478.83]
Not estimable
Not estimable
149.29 [8.34, 2672.76]
2.08 [0.58, 7.49]
5.11 [2.08, 12.54]

49/69
30/30
14/44
7/10
16/17
12/18
27/27
215

7.68
5.51
2.67
6.89
3.15
33.42

3.38 [1.32, 8.67]

Not estimable
1.22 [0.51, 2.96]
6.54 [1.21, 35.38]
5.36 [0.21, 139.28]
2.36 [0.73, 7.66]
0.05 [0.00, 0.88]
2.00 [0.80, 5.00]

0/28
0/92
120

2.93
2.93

Not estimable
4.04 [0.19, 85.18]
4.04 [0.19, 85.18]

821

100.00

03 Culture
0/34
Hardo et al. 1995
2/116
Oshowo et al. 1998
150
Subtotal (95% CI)
Total events: 2 (gastric positive), 0 (gastric negative)
Test for heterogeneity: not applicable
Test for overall effect: Z = 0.90 (P = 0.37)
1088
Total (95% CI)
Total events: 490 (gastric positive), 196 (gastric negative)
2
Test for heterogeneity: c = 53.37, df = 21 (P = 0.0001), I 2 = 60.6%
Test for overall effect: Z = 3.97 (P < 0.0001)

7.53

OR (random)
95% CI

3.61 [1.91, 6.82]

0.001 0.01 0.1

1
10
100 1000
Favours treatment
Favours control

Figure 1 Forest plot of the studies on the prevalence of Helicobacter pylori infection in the oral cavity in gastric H. pylori-positive patients
compared with gastric H. pylori-negative patients. Horizontal lines = 95% CI. The rectangles represent the point estimates of the study, and the
size of the rectangle represents the weight given to each study in the meta-analysis. The diamond represents the summary estimates; the size of the
diamond represents the CIs of the summary estimates.

signicant dierence between the two groups. The

eradication eciency in stomach is 85.8% (187 218),
while in oral cavity it is only 5.7% (9 158). The OR is
65.74, P < 0.0001 (Fig. 3), indicating that H. pylori in
stomach react more strongly to H. pylori eradication
therapy. Signicant heterogeneity was seen among
studies (P = 0.0006, I2 = 79.8%). Exclusion of any of
the studies did not eliminate the heterogeneity.

Discussion
Although extensive studies on the pathogenicity of
H. pylori have been conducted over the past decades,
the exact mode and route of transmission of the
bacteria is still unknown. Among various reports, the

fecal oral and oral oral routes have been suggested

most strongly (25). The detection of H. pylori in oral
cavity raises the possibility of other possible extra
gastric ecological niche for H. pylori. If the organisms
are present in the mouths of patients with gastritis, it
could be a reservoir for spread of the disease. Failure
to eliminate H. pylori from the mouth could lead to
recolonization in the stomach, accounting for recurrence of Helicobacter gastritis and associated duodenal
diseases. However, established studies carried out so
far to nd association between oral and gastric
H. pylori infections have revealed conicting results.
Some report a positive relation, while others deny any
association (26). In this meta-analysis, the prevalence
of H. pylori infection in oral cavity was signicantly
J Oral Pathol Med

Helicobacter pylori in the oral cavity and gastric mucosa

Q.-H. Zou and R.-Q. Li

322

Review:
Comparison:
Outcome:

Helicobacter pylori in the oral cavity and gastric mucosa: A meta-analysis

02 Case vs Control
01 Case vs Control

Study
or sub-category

Case
n/N

Morales et al. 2009

Umeda et al. 2003
Berroteran et al. 2002
Medina et al. 2010
Dore-Davin et al. 1999

34/66
18/45
12/32
15/43
12/17

203
Total (95% CI)
Total events: 91 (case), 21 (control)
2
Test for heterogeneity: c = 3.09, df = 4 (P = 0.54), I 2 = 0%
Test for overall effect: Z = 5.85 (P < 0.00001)

Control
n/N

OR (fixed)
95% CI

Weight
%

13/65
2/12
3/20
3/55
0/7

50.89
15.18
18.49
13.74
1.70
100.00

159

OR (fixed)
95% CI
4.25
3.33
3.40
9.29
34.09

[1.96,
[0.65,
[0.82,
[2.48,
[1.64,

9.24]
17.03]
14.08]
34.83]
707.92]

5.15 [2.97, 8.92]

0.001 0.01 0.1

1
10
100 1000
Favours treatment
Favours control

Figure 2 Forest plot of the studies on the prevalence of Helicobacter pylori infection in the oral cavity in patients with clinical and or histological
gastroesophageal disease compared with patients with non-ulcerous dyspepsia or healthy controls. Horizontal lines = 95% CI. The rectangles
represent the point estimates of the study. The diamond represents the summary estimates.

Review:
Comparison:
Outcome:

Helicobacter pylori in the oral cavity and gastric mucosa: A meta-analysis

03 therapy
01 eradication rate in stomach and oral cavity

Study
or sub-category
Dore-Davin et al. 1999
Gebara et al. 2006
Suk et al. 2002
Gurbuz et al. 2003
Ozdemir et al. 2001

Stomach
n/N
14/22
27/30
32/38
54/65
60/63

218
Total (95% CI)
Total events: 187 (stomach), 9 (oral cavity)
2
Test for heterogeneity: c = 19.76, df = 4 (P = 0.0006), I 2 = 79.8%
Test for overall effect: Z = 4.05 (P < 0.0001)

Oral cavity
n/N

OR (random)
95% CI

3/9
4/13
2/28
0/68
0/40

Weight
%
22.21
22.05
22.03
17.13
16.58
100.00

158

OR (random)
95% CI
3.50
20.25
69.33
649.26
1400.14

[0.68, 17.96]
[3.79, 108.25]
[12.90, 372.72]
[37.42, 11265.73]
[70.42, 27836.85]

65.74 [8.69, 497.46]

0.001 0.01 0.1

1
10
100 1000
Favours treatment
Favours control

Figure 3 Eradication rate of Helicobacter pylori in stomach and oral cavity. Horizontal lines = 95% CI. The rectangles represent the point
estimates of the study. The diamond represents the summary estimates.

increased in gastric H. pylori-positive patients compared with gastric H. pylori-negative patients

(OR = 3.61, 95% CI: 1.916.82) in the 22 studies,
indicating an association between H. pylori infections
in oral cavity and stomach. With regard to the role of
oral cavity in the transmission of H. pylori infection,
data from the literature vary greatly (9, 1214, 20). A
wide range of detection rates (from 0% to 100%) has
been observed in oral samples owing to dierences in
sample collection and H. pylori-detecting techniques
(27, 28). We carefully performed subgroup analysis and
found dierent diagnostic methods did not change the
results that the prevalence of H. pylori infection in oral
cavity was signicantly increased in gastric H. pyloripositive patients compared with gastric H. pylori-negative patients, but they contribute to the variation of
the pooled estimates because of their dierent sensitivities. The pooled OR value increased with the sensitivity of the diagnostic method. Therefore, PCR, which
has the highest sensitivity of the three tests used,
obtained the highest pooled OR, while culture method
yielded the lowest OR because the presence of a viable
coccoid form is usually unculturable by conventional
techniques. For the PCR method, pooled ORs vary
J Oral Pathol Med

signicantly between dierent primers from 15.16 for

860 -bp fragment to 1.71 for urease or cagA gene. To
date, a host of primers have been used, including those
based on the urease genes, 16S ribosomal RNA genes,
860 -bp fragment, and randomly selected DNA fragments. Unfortunately, the sensitivity and specicity
dier among the primers, and the most appropriate
method for the detection of oral H. pylori has yet to be
established (29, 30).
Sensitivity analysis was performed in several ways to
test concordance of the results by changing the statistical methods used. The sensitivity analyses that were
performed did not materially change the results,
increasing the condence that can be placed in these
results when applying the conclusion in practice.
Helicobacter pylori are a major human gastric pathogen responsible for gastritis and peptic ulcer disease.
This meta-analysis revealed 44.8% (91 203) prevalence
of this bacteria in the oral cavity in patients with clinical
and or histological gastroesophageal disease compared
with 13.2% (21 159) in patients with non-ulcerous
dyspepsia or healthy controls (OR = 5.15, CI: 2.97
8.92, P < 0.00001), indicating H. pylori in the oral
cavity is associated with gastroesophageal disease.

Helicobacter pylori in the oral cavity and gastric mucosa

Q.-H. Zou and R.-Q. Li

Several studies have reported low eradication rates of

H. pylori from DP (16, 17). The lack of eect of systemic
therapy on H. pylori in DP may be explained by the
structure of DP that contains proliferating microorganisms, along with a scattering of epithelial cells, leukocytes, and macrophages (31), which made H. pylori
harbored in DP inaccessible to systemic antibiotic
therapy. Reinfection of the stomach by the identical
strain has been reported (32). We found signicant
dierences in the rates of eradication success between
stomach and oral cavity (85.8% vs. 5.7%) in our metaanalysis, indicating that oral cavity can serve as a
permanent reservoir of H. pylori, and it can also be a
potential source for gastric reinfection after successful
systemic therapy.
Before concluding, several limitations of this study
must be considered. First, the quality of a meta-analysis
depends on the quality of the original studies, particularly the study design and reporting. There was evidence
of heterogeneity in subgroup analyses, which suggested
a diversity of study design, dierent H. pylori testing
methods, etc. may have an unfavorable inuence on the
interpretation of the results. Second, some studies used
several methods for H. pylori identication. However,
detailed information about the conrmation of H. pylori
infection by all or any one of the tests is not provided.
This might result in dierent infection rates in the
studies and therefore bring signicant heterogeneity in
the studies. Third, we excluded non-English publications
and unpublished studies, which also might introduced
selection bias.
In summary, our results show that the prevalence of
H. pylori infection in the oral cavity is signicantly
higher in gastric H. pylori-positive patients compared
with gastric H. pylori-negative patients. It is also higher
in the oral cavity in patients with clinical and or
histological gastroesophageal disease compared with
patients with non-ulcerous dyspepsia or healthy controls. The eradication rate is signicantly higher in
stomach than in oral cavity. These results suggest
H. pylori-infected DP, saliva, or other places in the
oral cavity may be a source for infection and reinfection. It is therefore suggested that professional plaque
removal and oral hygiene procedures be performed,
along with the antibiotic treatment of H. pylori in
patients presenting H. pylori detection in the oral
cavity.

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Acknowledgements
Zou Qinghua has served as a teacher for Peking university health
science center and has received research funding from Peking
University. This study was supported by Research Funds for the
Central Universities of Peking University, grant number 891ja-213741-132.

Author contributions
QHZ designed the research, analyzed the data, and produced the
manuscript; RQL collected the data and helped analyze the data.