DOI: 10.1111/ipd.
12364
REVIEW
Effects of Papacarie on children with dental caries in primary
teeth: a systematic review and meta-analysis
YUEJIA DENG1,2,3,#, GE FENG1,2,3,#, BO HU1,2,3, YUNCHUN KUANG1,2,3 & JINLIN SONG1,2,3
1
College of Stomatology, Chongqing Medical University, Chongqing, China, 2Chongqing Key Laboratory for Oral Diseases
and Biomedical Sciences, Chongqing, China, and 3Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of
Higher Education, Chongqing, China
International Journal of Paediatric Dentistry 2018; 28:
361–372
Background. Caries in primary teeth hinder the
child to bite and chew and influence their devel-
opment. Papacarie has the characteristics of selec-
tive removal of decayed tissue and can preserve
healthy dentine to the maximum, but its effi-
ciency has not been critically evaluated compared
to conventional method.
Aim. This review is aiming at comparing the Papa-
carie and traditional method in caries removal in
primary dental caries with children.
Design. Comprehensive literature searching at
PubMed, Embase, Cochrane Central Register of
Controlled Trials, and Web of Science to January
2018.
Introduction
Dental caries are among the most general
dental diseases among children, as a result of
the consumption of too much candied food,
carbonated drinks, and lack of regular oral
examination1,2. Dental caries usually destruct
and dissolve the tooth tissues locally and may
lead to the pulpitis and periapical periodonti-
tis, and eventually result in teeth missing
when left untreated, which causes patients to
have pain and discomfort3. Because the
enamel on primary teeth is less calcified and
more fragile, primary teeth are more subject
to lesion formation and progression than are
permanent teeth4,5. Primary teeth, however,
helps to develop a proper occlusion in young
*Correspondence to:
Jinlin Song, Stomatological Hospital affiliated to Chongqing
Medical University, Chongqing 401147, China.
E-mail: soongjl@163.com
#Both authors made equal contribution to this work.
© 2018 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Results. Six randomized controlled trials (RCTs)
and four prospective controlled clinical trials
(CCTs) were included. The microbiota in caries
dentine was significantly reduced using the Papa-
carie treatment (MD = 0.57, 95% CI 0.04 to 1.09,
P = 0.03), and the anxiety feeling declined more
in the Papacarie group (MD = 1.01, 95% CI
1.72 to 0.30, P < 0.005). There was a greater
200.79 (MD = 200.79, 95%CI 152.50 to 249.09,
P < 0.00001) increase in time taken for the Papa-
carie treatment compared with the conventional
method.
Conclusion. Papacarie exerts a positive effect in
reducing the bacteria and decreases the pain dur-
ing caries removal in primary teeth although it
costed a longer treatment time compared with the
conventional method.
children, because primary teeth maintain a
particular space and served as space retainers
for the permanent teeth, and healthy primary
teeth are significant in helping children to
bite and chew, speak clearly, and promote
self-confidence6. Hence, caries removal and
restoration (fillings) for the primary teeth are
a necessary option for the management of
oral health in children.
Conventional caries removal method usu-
ally means digging and drilling by rotation
handpiece to remove the decayed tissue3,
which is efficient in removing the bacterial
dentine but is perceived as uncomfortable,
uneasy, and painful by children7–9. Because
conventional caries removal method may
extend into the sound dentin in the inner,
thereby it is therefore to open more dentinal
tubules. This effect is usually prone to bring-
ing pain and tension. And the use of local
anaesthesia is necessary during treat-
ment10,11.
361
362 Y. Deng et al.
Currently, painless treatment and minimal
intervention are basic principles in paediatric
dentistry12. The treatment principles of dental
caries were transformed by the advances of
the physiology and the progress in minimally
invasive treatment. The most conspicuous
changes contain the selective removal of bac-
terial dentine and preservation of sound den-
tine to the maximum13–15. Alternative
techniques, such as lasers, air abrasion, ultra-
sonic technique, and Chemomechanical
approaches for caries removal, have been
developed. Among these methods, most of
them except Chemomechanical approaches
are costly and may lead to the hypersensitiv-
ity of teeth and therefore infrequently used16.
In addition, these methods cause pressure on
the pulp and deleterious thermal, which con-
tribute to pain and anxiety especially in chil-
dren17. Therefore, the Chemomechanical
method is one of the most documented alter-
native to conventional drilling method18.
Recently, in 2003, Papacarie was released
as a proteolytic gel19. The collagen degrada-
tion features of papain and the bactericide
characteristics of chloramines were added to
the new medicine13,20. Papain makes the cari-
ous dentine softer through the interaction
with exposed collagen and then dissolute the
decayed tissues, which allows the removal of
carious dentine without local anaesthesia and
drilling. Flindt21 demonstrated that papain’s
function limited in bacterial tissues because
infected tissues lack a plasmatic anti protease,
known as anti-trypsin (AI), this is only pre-
sent in healthy dentine and it inhibits tooth
structure destroyed. Dawkins et al.22 reported
that papain can inhibit the growth of Gram-
positive and Gram-negative organisms. This
technique involves the selective removal of
degraded collagen fibrils in carious dentin
lesions, while preserving the affected dem-
ineralized dentine layer23. Adopting the Papa-
carie method in caries removal, clinicians can
remove all of the caries dentine and protect
the sound dentine without a special instru-
ment. Most children are satisfied with this
method, according to research on their prefer-
ence research of the conventional method
and Papacarie24,25. Several investigators, how-
ever, have noted the efficacy of Papacarie is
© 2018 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
questionable13,26,27, and it may increase the
treatment time28–30. This inconclusive evi-
dence is not advantageous for clinical applica-
tion and the promotion of Papacarie for caries
removal in primary teeth among children.
Therefore, a scientific systematic review and
meta-analysis are necessary to evaluate the
effectiveness and efficient of Papacarie31 in car-
ies removal in primary teeth in children. The
evidence-based systematic review and meta-
analysis aim to determine whether the applica-
tion of Papacarie could influence the outcomes
of caries removal with primary teeth in chil-
dren. Specifically, we focus on these outcome
variables as follows: including a microbiological
assessment before and after caries removal and
the influence on child behaviour, pain percep-
tion, length of time needed, and preference of
the treatment method by children.
Method
This systematic review was performed refer-
ring to the guidelines of the PRISMA state-
ment for reporting systematic reviews.
Focused question
According to the PICO framework: ‘Is the effi-
ciency and efficacy of Papacarie in primary
dental caries with children better when
compared to conventional drilling method
(controls)?’
Literature search
We conducted a comprehensive search in
PubMed, Embase, Cochrane Database of Sys-
tematic Reviews, Cochrane Central Register
of Controlled Trials, Ovid, Google Scholar,
and Web of science up to 20 January 2018.
The following key words were used in litera-
ture searches: ‘primary teeth’, ‘caries’, ‘Papa-
carie’, ‘Chemomechanical Caries Removal’,
and ‘Chemomechanical Caries Excavation’.
The language or date of publication was not
limited and searched the reference lists of all
researches for additional studies. Where addi-
tional data and figure for some literature
were needed, we contacted the related
authors.

Inclusion criteria (PICO question: population,
intervention, comparison, outcome). Type of partic-
ipants—Adolescent and child patients with
primary molar caries. Only human studies
were included without gender restriction.
Children without intelligence problem or
without receiving sedatives before treatment
or any related agents for procedural sedation
will be included in this study.
Type of interventions—Patients undergoing
Chemomechanical caries removal (Papacarie)
or conventional caries removal method in the
primary molar teeth.
Types of outcome measures—Microbiological
assessment before and after the caries
removal, influence on child behaviour, pain
perception, length of time needed, and prefer-
ence of treatment method by children were
recorded separately for both the methods.
Trial design—RCTs and prospective CCTs were
reviewed, included, and analysed accordingly.
Exclusion criteria
The following types of studies were
excluded: (i) restorative treatment; (ii)
studies involving teeth with enamel hypo-
plasia and other structure defects; (iii)
studies lack the mean value and standard
deviation (SD) of outcomes including time
needed to take, pain scale, microbiota
reducing before and after caries removal;
(iv)When children have presence of spon-
taneous pain, use of antibiotics within
2 weeks prior to study, teeth with pulpal
involvement, furcation or periapical
pathology and/or interproximal caries and
presence of any systemic disease;(v)stud-
ies that conducted in permanent teeth.
Data extraction
The titles, author, and A. A. (date) of
retrieved articles were imported into Endnote
X7. Then, two reviewers (* and *) invested
independently to evaluate the eligibility of
the studies. Any dissents were resolved by
© 2018 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Chemomechanical caries removal method 363
conversation. In addition, a third author (*)
was consulted if needed.
We choose publications according to the
inclusion criteria and exclusion criteria. Then,
we get full texts for all eligible studies. Data
are extracted as follows: (i) author and publi-
cation year; (ii) study type; (iii) characteristics
of participants: sample size, age, location,
group, and overall health conditions; (iv) car-
ies type, moisture control, criteria of caries
removal, scale type of pain, outcome vari-
ables, and authors’conclusions, among others.
Quality assessment
The Cochrane Handbook on Risks of bias31
was adopted to evaluate the quality of the eli-
gible studies independently by two reviewers
(* and *). For each study, in brief, the selec-
tion bias, performance bias, detection bias,
attrition bias, reporting bias, and other bias
are assessed. The classification of the parame-
ters was adequate, unclear, or inadequate32.
A study was evaluated as ‘low risk of bias’ if
all the domains were judged as ‘low risk’,
‘moderate risk of bias’ if any of the domains
was judged as ‘unclear risk’, and ‘high risk of
bias’ if any domain was judged as ‘high risk’.
All these data were assessed by two reviewers
(* and *), and dissents were settled by discus-
sion or consultation with a third author (*).
The decisions on study identification were
recorded.
Data analysis
The multiple studies were combined by the
weighted mean difference (WMD), standard
deviation (SD), and its 95% confidence inter-
vals (CIs) of the outcome variable (the CFU
of bacteria, scores of pain scale, and treatment
time) were assessed. We analyse the extracted
data using Review Manager 5.3. Statistical
heterogeneity was explored using the chi-
square test with a 10% level of significance as
the cut-off value. I2 statistic was used to
quantify the impact of statistical heterogene-
ity. And a 95% confidence interval (CI) of I2
is reported in addition to the point estimate
I2. If I2 > 50% (P ≤ 0.10), which means a
high heterogeneity. Then, the heterogeneity
364 Y. Deng et al.
needs to be explained, a random-effect model
was used, otherwise, the fixed-effect model
would be chosen. The hypothesis of homo-
geneity was set invalid for P < 0.05 (2-tailed z
tests). If the data were unable to be pooled,
they were described.
Results
Studies selection results
In total,203 articles are identified through
databases and hand search. A total of 188
studies were removed because they do not
meet the inclusion criteria. Fifteen articles
with adequately designed and particular
treatment method are involved in the quali-
tative synthesis. Three of the studies are
excluded for the deficiency of mean and SD
data, and three of them reported the same
experiment. Finally, six RCTs and four CCTs
are involved in the quantitative synthesis.
The flow diagram of study selection is dis-
played in Fig. 1.
Studies features
The trials’ publication date was from 2009 to
2016. Among these trials, three articles
reported the same experiment33–35; therefore,
they were combined as Motta 2013–2014.
Different regimens of the Papacarie method
were identified in the included articles. The
type, generation, and dose of the medicine
are different. Among the included studies,
five trials24,28,34,36,37 discussed the change in
bacteria in the caries lesion, and two24,36 tri-
als were excluded in the meta-analysis for a
lack of mean and SD data. In addition, 10 tri-
als24–26,33,34,38–42 assessed the outcomes of
pain perception before and after different car-
ies removal methods; nevertheless, the scales
used in these trials differ considerably. Only
three trials25,28,42 used the Wong-Baker-Face
Pain Scale (WBF) to evaluate pain perception
and were remained eligible. And seven trials
with complete mean and SD data of time-
consumption were included in the meta-ana-
lysis. Table 1 shows the summary of the
features of included studies.
© 2018 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Risk of bias
A review of the judgement of the authors
concerning each risk bias item is presented in
Fig. 2, and the assessments of each study’s
risk of bias are listed in Fig. 3. Nine of them
had a low risk of bias, and the other five
studies had a moderate risk of bias. Among
the eligible researches, three of them did not
make a clear description of the enrolment. As
blinding of operators was impossible because
operators were clear regarding the treatment
type during the treatment, the evaluation of
blinding here referred to the data analysers.
To avoid detection bias, all the outcome vari-
ables were previously calibrated. The other
two studies did not notice the blinding of out-
come assessment.
Efficacy of Papacarie treatment in reducing the
cariogenic microbiota
Five trials reported the outcome for reducing
bacteria. Three of these have a data deficiency
or differed in the bacteria measurement
method. As a result, these trials are excluded
in the meta-analysis. Two studies with a
detailed mean and SD data of log10 colony
forming units (CFUs) were adopted to be used
for a meta-analysis and the forest plot was
demonstrated in Fig. 4. In sum, 90 patients
contributed to this outcome. It was observed
that the microbiota in caries dentine was sig-
nificantly reduced using the Papacarie treat-
ment (MD = 0.57, 95% CI 0.04 to 1.09,
P = 0.03), compared with the conventional
drilling method, with low heterogeneity
detected (v2 = 2.00, P = 0.37, I2 = 0%, 95%
CI 0%–98%).
Pain perception
Ten studies discussed the pain perception
when caries in the primary teeth were treated.
Means and SD data of Wong-Baker-FACES
(WBF) scores, however, were provided by
three studies for meta-analysis. The forest plots
were displayed in Fig. 5. Although WBF score
is a subjective measurement, it is the relatively
easy and convenient way to record the feeling
of child patients when they had been treated.

Fig. 1. PRISMA diagram to show the process of study selection.
It was observed that pain scores evaluated
before and after caries removal were reduced
in both the Papacarie and conventional
method. Because I2 = 86% (95%CI 60%–
95%) showed high degrees of heterogeneity
between studies, a random-effect model was
adopted. When comparing the two groups, the
anxiety feeling declined more in the Papacarie
group (MD = 1.01, 95% CI 1.72 to 0.30,
P < 0.005).
© 2018 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Chemomechanical caries removal method 365
Time taken for caries removal
Eight researches demonstrated the outcomes
of the treatment time. Nevertheless, only
seven were eligible for the meta-analysis. The
forest plot was described in Fig. 6. There was
a greater, that is, 200.79 (MD = 200.79, 95%
CI 152.50 to 249.09, P < 0.00001) increase in
time taken for the Papacarie treatment com-
pared with the conventional method. The
 Table 1. Characteristics of the included studies (n = 13). 366

Sample Age Number Moisture Pain Scale Treatment time

Study Country Design size (years) of teeth Caries type Group control type mean (SD)

Ammari (2014) Brazil RCT, parallel 46 5–9 74 Dentine Papaca
rie (n = 25), Carisolv Cotton rolls – –
(n = 27)
Manual (n = 22)
Anegundi (2012) India RCT, parallel 30 4–9 60 Dentine CM (n = 30) Rubber dam FBS –
Papac
arie (n = 30)
Y. Deng et al.

Magda (2011) Egypt RCT, parallel - 4–8 45 Dentine Papac
arie (n = 15) Rubber dam; - -
Carisolv (n = 15)
hand excavation (n = 15)
Motta (2013) Brazil RCT, split mouth 20 4–7 40 Dentine Papacarie (n = 20) Cotton roll FES Papacarie
CM(n = 20) 279.6 (187.8)
CM
198 (121.8)
Goyal (2015) India RCT, parallel 25 5–9 50 Dentine CM (n = 25) Rubber dam WBF –
Papacarie (n = 25)
Gulsheen (2011) India RCT, parallel 80 5–9 120 Dentine Hand instruments (n = 30) Rubber dam VAS Papacarie
Airrotor (n = 30) 590.8 (187.004)
Carisolv (n = 30) CM
Papacarie (n = 30) 261.7 (86.06)
Mariya (2012) India CCT, parallel - 5–9 120 Dentine Airrotor (n = 30), Rubber dam FLACC Papacarie
Carisolv (n = 30), 471.3 (68.2)
Papacarie (n = 30) CM
Er:YAG laser (n = 30) 206.7 (22.1)
Maru (2014) India RCT, parallel 60 3–5 60 Dentine Conventional method Cotton wool rolls WBF -
(n = 30) Papacarie approach
(n = 30)
Mastumoto (2013) Brazil RCT, split mouth 20 5–8 40 Dentine Papacarie (n = 20) Cotton roll and FES –
CM (n = 20) saliva suction device
Sanjeet (2011) India CCT, parallel 40 4–8 80 Dentine CM (n = 40) Rubber dam placement. WBF Papacarie
Papacarie (n = 40) 328.5 (45.3)
CM
124.6 (22.8)
Sapna (2016) India RCT, parallel 50 5–12 150 Dentine CM (n = 50) Cotton roll isolation WBF Papacarie
Carisolv (n = 50) with suction 322.49 (91.24)
Papacarie (n = 50) CM
61.34 (30.43)
Kotb (2009) Egypt CCT, split mouth 37 5–9 74 Dentine Papacarie (n = 37) Cotton roll SEM Papacarie
CM (n = 37) 293.4 (63)
CM
270 (109.8)
Swati (2015) India RCT, parallel 30 6–9 90 Dentine CM (n = 30) Rubber dam – Papacarie
carisolv (n = 30) 387.83 (38.53)
Papacarie (n = 30) CM
171.27 (23.22)

© 2018 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Fig. 2. Risk of bias graph. Review authors’ judgements about each risk of bias item presented as percentages across all
included studies. Red, yellow, and green refer to high risk of bias, unclear risk of bias, and high risk of bias.
results of the time taken had a high hetero-
geneity (v2 = 128.89, P < 0.00001, I2 = 95%,
95%CI 93%–97%). Maybe the different stud-
ies lack of consistency regarding the measure-
ment and analysis of the time. Therefore, we
chose random effects model to describe the
outcomes.
Patient acceptability
The preference of the different caries removal
method was evaluated in three studies. Ane-
gundi24 recorded the preference of the con-
ventional method and Papacarie, in which
the Papacarie group had a higher proportions
of 60% compared with 36.7% for the con-
ventional method. In Goyal’s study28, a
majority (80%) of the children in the study
preferred the Papacarie method. In addition,
Swait25 compared the conventional method,
Carisolv and Papacarie for patient acceptabil-
ity through a visual analogue scale (VAS). In
their study, the patient acceptance rate was
observed to be higher with Papacarie method.
These results can be explained by the fact
that less pain and anxiety were experienced
in patients with the Papacarie method. This
finding is in accordance with the results of
pain perception scaled by Wong-Baker-
FACES (WBF) scale.
Follow-up
According to all of the included studies, only
two studies reported the long-term follow-up
of the Papacarie method. One study26
recorded the retention of the filling material
and the incidence of secondary caries
1 month later, and the use of a different
© 2018 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Chemomechanical caries removal method 367
caries removal method was analysed. In addi-
tion, the restoration was predominantly pre-
sent and without defects following both
procedures. In the other study33, the partici-
pants received regular clinical follow-up of
the caries treatment. The density of the
remaining dentin was assessed through radio-
graphic examination. The record time
includes immediately after the caries removal
treatment and one (T1), six (T2), and 18 (T3)
months later. In both groups, the mean radio-
graphic density was improved after treatment
in different evaluation times, and no sec-
ondary decay was observed in the two
groups.
Discussion
Painless dentistry and minimal intervention
providing comfort, relief, solace, and instilla-
tion of a positive attitude towards dental
health care are among the factors justifying
the specialty of paediatric dentistry30. A gen-
tle and painless treatment experience may
affect the patients’ whole life of oral health30.
Because many of the school-age children are
afraid of the dentist, they may consequently
avoid dental care19. This negative behaviour
is often linked to early traumatic experiences
and negative attitudes in the patient’s fam-
ily43. Consequently, fearful dental patients
often do not receive optional and regular
dental care. Thus, minimal invasive caries
removal treatment is of great importance in
dental care for children. In addition, the con-
cept of preserving sound dentine in the Che-
momechanical caries removal (CMCR)
method is of great interest among dental
researchers and patients44. Chemomechanical
368 Y. Deng et al.
Fig. 3. Risk of bias graph: the review authors’ judgements
about each risk of bias item for each included study. Green,
yellow, and red refer to low risk of bias, unclear risk of bias,
and high risk of bias, respectively.
caries removal (CMCR) is a non-invasive
intervention that removes decayed dentine,
preserves sound dental tissues, and avoids
pulp annoyance and patient discomfort45.
Recently, Papacarie has been established as a
Chemomechanical caries removal method,
© 2018 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
which is a combination of papain, chlo-
ramine, toluidine blue, and salts that facili-
tates removal of the decayed tissue.
Papain, which is the basic component of
Papacarie, is responsible for its bactericidal,
bacteriostatic, and anti-inflammatory proper-
ties. In addition, Papacarie was observed to
have no ability to destroy the underlying
healthy collagen fibres and sound dentine, as
Papain can digest only dead cells46. The ease
of application and no need for special devices
is an added advantage of Papacarie25. Cur-
rently, many clinical studies10,22,25,30,38,39
have been conducted to evaluate its efficiency
in caries removal. The main outcome vari-
ables discussed in these researches studies are
bacteria removing efficiency, pain perception,
and time taken for caries removal. These
research findings, however, were inconsistent
and hinder the clinical application of Papa-
carie. There is a great deficiency of systematic
review on the efficacy of the Papacarie
method in caries removal in primary teeth. In
addition, a previous published systematic
review of Chemomechanical caries removal
(CMCR) primarily considers only permanent
teeth and research is lacking on primary
teeth. Primary teeth, however, are more
prone to lesion formation and progression
than permanent teeth4,5, and caries in pri-
mary teeth influence the children in biting,
chewing, speaking, and their self-confidence.
In addition, the outcome variables in previous
systematic reviews are also limited. Mainly
previous studies only compare the treatment
time29. Therefore, there is a lack of the com-
parison in reducing the cariogenic microbiota
before and after the caries removal and pain
perception in caries removal treatment.
Hence, we performed a systematic review and
meta-analysis in an attempt to elucidate the
effectiveness and reliability of the Papacarie
method.
Interpretation of the results
A bacteriological analysis was chosen as the
method of assessment chosen in this study to
test the effectiveness of both methods (con-
ventional drilling method and Papacarie) for
the completeness of caries removal13,24,30. A
 Chemomechanical caries removal method 369

Fig. 4. Forest plot from the fixed-effect meta-analysis evaluating the difference in bacterial before and after caries removal
treatment.

Fig. 5. Forest plot from random effects meta-analysis for the comparison of Wong-Baker-FACES (WBF) scores in conventional
method and Papacarie treatment.

Fig. 6. Forest plot from the fixed-effect meta-analysis evaluating the difference in time taken of caries removal.

reduction in the cariogenic bacterial counts bacterial counts of no clinical significance.

responsible for the occurrence of dental caries
was monitored as the presence of bacteria has
been considered by many investigators to
be an accurate indicator of infected carious
dentine28,30.
Five included studies discussed bacteria
removal, but only two studies reported the
specific results of colony forming units (CFU)
reduction and included in the meta-analysis,
which demonstrated that Papacarie could sig-
nificantly decrease the bacteria remains in
residual dentine more compared to the con-
ventional drilling method. That finding is
observed because Papacarie possesses a potent
antimicrobial effect on all cariogenic bacteria,
especially lactobacilli, as it diffuses by its low
viscosity through the open dentinal tubules
and eliminates cariogenic bacteria and thus
leaves the cavity clean or even yielding
And the heterogeneity of the colony forming
units (CFU) reduction is I2 = 0% (95%CI
0%–98%). The point estimate I2 is low, but
the range of 95% confidence interval (CI) of
I2 is relatively broad. So the I2 statistic is not
that precise to evaluate the heterogeneity.
And the small number of studies included for
the outcome induced the heterogeneity.
Pain perception is a very subjective judge,
and various scales have been used to record
the children’s feeling after caries removal.
Pain perceptions were recorded by Wong-
Baker-FACES (WBF) scores using the WSF
Pain Rating Scale before and after different
treatment methods in the included stud-
ies25,28,42. Three studies were included in the
present research, and the quality analysis
shows that among the three studies, two had
a low risk of bias, and the other one study

© 2018 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
370 Y. Deng et al.
had a moderate risk of bias, thus, the
included data are reliable. Because pain per-
ception is a very subjective judge, children’s
personality and dental experience explained
the heterogeneity (I2 = 86%, 95%CI 60%–
95%). We observed that the patients experi-
ence considerably more pain when treated
with the conventional drilling method
because the loud noise and pressure on the
sound dentine could cause additional pain.
Contrary to the conventional drilling method,
the Papacarie would only have a function for
dead cells, and the dentine would be pro-
tected more completely. That property is close
to the minimal invasive concept of paediatric
dentistry. Only in this way can we protect as
much sound dentin as possible and provide a
patient relief during caries treatment.
Although several studies19 also suggested that
the patient’s fear of the dentist increased in the
Papacarie group and decreased slightly in the
conventional drilling method group. These
researchers attributed this outcome to the
longer treatment time needed for the CMCR
group.
In this paper, we chose treatment time as
an outcome to evaluate the efficacy and effi-
ciency of caries removal in different methods.
Among the seven studies, we made a conclu-
sion that the Papacarie method is more time-
consuming than the conventional method.
The heterogeneity of treatment time is, how-
ever, high, and it can be explained by that
there is a lack of consistency guideline of the
measurement of treatment time. Next, when
we conducted the sensitivity analyses, I2 was
95% (95%CI 93%–97%), and a high hetero-
geneity still existed. This finding may be
explained by the different location of the car-
ies lesion, the size of the lesion and the differ-
ent experiment environment. Despite all of
the confounding factors above, the hetero-
geneity of our study is acceptable. In addition,
a more strong conclusion needs further ran-
domized controlled trials of good quality.
Advantages and limitations of the review
Several meta-analyses analysed the applica-
tion of Chemomechanical caries removal in
dental caries. Different from either published
© 2018 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
meta-analysis, the pain perception and evalu-
ation of the reduction of the cariogenic
microbiota, however, were finite. Few
reviews have been completed on this topic. In
the present study, we searched all of the
related researches with only the inclusion of
caries removal used in primary teeth were
included. In our study, strict inclusions were
implemented, and those studies comparing
the efficient of caries removal methods
between permanent teeth were excluded
from this analysis. Risk of bias was minimized
through rigorous study design and that
increased reliability in the conclusion. More
outcomes, such as patients’ acceptance and
follow-up of the restorations, have also been
evaluated in this study.
Several limitations of the present study
should be recognized. First, all of the studies
were conducted in India, Egypt, and Brazil,
which limits the generalizability of the
results. Hence, discrepancies in the caries
removal among countries might have influ-
enced the results. More clinical studies con-
ducted in different countries are needed.
Second, the power of formal tests was limited
in this meta-analysis due to the lack of a
long-term follow-up of the restorations,
which indicates meaning that potential publi-
cation bias might have influenced our find-
ings. Furthermore, it is necessary to use the
subsequent caries rate as an outcome to eval-
uate the efficacy of Papacarie. Third, the car-
ies type is not clear in the limited included
studies, and the location of the caries may
influence the efficacy of the caries removal.
Further criteria regarding the baseline of car-
ies type and specific treatment procedures
may minimize heterogeneity between trials.
Conclusions
Papacarie is effective and efficient with the
feature of selective caries removal considering
the minimal invasive philosophy in paediatric
dentistry. Papacarie displayed advantages in
reducing the bacteria in carious dentine and
decreasing the pain perception during caries
removal in primary teeth among children,
although it had a longer treatment time com-
pared with the conventional method. Further

studies applied Papacarie in caries removal in
primary teeth in different countries are
required.
Why this paper is important to paediatric
dentists
• It compared the efficiency of conventional
caries removal method and Papacarie, which
would help paediatric dentists to make treat-
ment choices on their clinics based on the
best scientific evidence available.
• Paediatric dentists could know that Papa-
carie is an alternative to conventional caries
removal method when making treatment
choice for children who are afraid of drills
and burs.
• It explores the significance of following
the painless treatment and minimal interven-
tion principles in paediatric dentistry.
Acknowledgements
The authors would like to thank Chunjie Li,
Professor, West China College of Stomatology,
Sichuan University, for his contribution to
the literature research and the methods in
this study. This study was supported by the
Program for Innovation Team Building at
Institutions of Higher Education in Chongqing
in 2016 (grant no. CXTDG201602006).
Author contributions
Yuejia Deng and Ge Feng searched the litera-
ture and selected the studies. Yuejia Deng, Bo
Hu, and Yunchun Kuang analysed the data
and drafted the article. Ge Feng and Jinlin
song designed the study, interpreted the data,
and revised the article.
Conflict of interest
The authors declare no conflict of interest.
References
1 Musaiger AO, Takruri HR, Hassan AS, Abutarboush
H. Food-based dietary guidelines for the Arab Gulf
countries. J Nutr Metab 2012; 2012: 905303.
© 2018 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Chemomechanical caries removal method 371
2 Sohn W, Burt BA, Sowers MR. Carbonated soft
drinks and dental caries in the primary dentition. J
Dent Res 2006; 85: 262.
3 Li R, Zhao Y, Ye L. How to make choice of the cari-
ous removal methods, Carisolv or traditional dril-
ling? A meta-analysis. J Oral Rehabil 2014; 41: 432–
442.
4 Fejerskov O, Larsen MJ, Richards A, Baelum V.
Dental tissue effect of fluoride. Adv Dent Res 1994; 8:
15–31.
5 Lynch RJM. The primary and mixed dentition, post-
eruptive enamel maturation and dental caries: a
review. Int Dent J 2013; 63(Suppl s2): 3–13.
6 Yengopal V, Harnekar SY, Patel N, Ni S. Dental fill-
ings for the treatment of caries in the primary denti-
tion. Cochrane Database Syst Rev 2016; 10(2):
CD004483.
7 Berggren U, Meynert G. Dental fear and avoidance:
causes, symptoms, and consequences. J Am Dent
Assoc 1984; 109: 247.
8 Green RM, Green A. Adult attitudes to dentistry
among dental attenders in South Wales. Br Dent J
1985; 159: 157–160.
9 Ayer WA Jr, Domoto PK, Gale EN, Joy ED Jr, Mel-
amed BG. Overcoming dental fear: strategies for its
prevention and management. J Am Dent Assoc 1983;
107: 18.
10 Allen KL, Salgado TL, Janal MN, Thompson VP.
Removing carious dentin using a polymer instru-
ment without anesthesia versus a carbide bur with
anesthesia. J Am Dent Assoc 2005; 136: 643.
11 Rafique S, Fiske J, Banerjee A. Clinical trial of an
air-abrasion/chemomechanical operative procedure
for the restorative treatment of dental patients. Car-
ies Res 2003; 37: 360–364.
12 Gupta S, Singh C, Yeluri R, Chaudhry K, Munshi
AK. Clinical and microbiological evaluation of the
carious dentin before and after application of Papa-
carie gel. J Clin Pediatr Dent 2013; 38: 133–138.
13 Ammari MM, Moliterno LFM. Remocß~ ao qu
ımico-
mec^ anica da c
arie: evid^
encias atuais. Rev Bras Odontol
2005; 62: 125–127.
14 Bussadori SK, Castro LC, Galv~ ao AC. Papain gel: a
new chemo-mechanical caries removal agent. J Clin
Pediatr Dent 2005; 30: 115.
15 Chadwick BL, Evans DJ. Restoration of class II cavi-
ties in primary molar teeth with conventional and
resin modified glass ionomer cements: a systematic
review of the literature. Eur Arch Paediatr Dent 2007;
8: 14–21.
16 Maragakis GM, Hahn P, Hellwig E. Clinical evalua-
tion of chemomechanical caries removal in primary
molars and its acceptance by patients. Caries Res
2001; 35: 205–210.
17 Anusavice KJ, Kincheloe JE. Comparison of pain
associated with mechanical and chemomechanical
removal of caries. J Dent Res 1987; 66: 1680.
18 Pandit IK, Srivastava N, Gugnani N, Gupta M,
Verma L. Various methods of caries removal in
372 Y. Deng et al.
children: a comparative clinical study. J Indian Soc
Pedod Prev Dent 2007; 25: 93.
19 Inglehart MR, Peters MC, Flamenbaum MH, Eboda
NN, Feigal RJ. Chemomechanical caries removal in
children: an operator’s and pediatric patients’
responses. J Am Dent Assoc 2007; 138: 47–55.
20 Bussadori SK, Guedes CC, Bachiega JC, Santis TO,
Motta LJ. Clinical and radiographic study of chemi-
cal-mechanical removal of caries using Papac
arie:
24-month follow up. J Clin Pediatr Dent 2011; 35:
251–254.
21 Flindt M. Health and safety aspects of working with
enzymes. Process Biochem 1978; 13: 3–7.
22 Dawkins G, Hewitt H, Wint Y, Obiefuna PC, Wint B.
Antibacterial effects of Carica papaya fruit on com-
mon wound organisms. West Indian Med J 2003; 52:
290.
23 Beeley JA, Yip HK, Stevenson AG. Chemo chemical
caries removal: a review of the techniques and latest
developments. Br Dent J 2000; 188: 427–430.
24 Anegundi RT, Patil SB, Tegginmani V, Shetty SD. A
comparative microbiological study to assess caries
excavation by conventional rotary method and a
chemo-mechanical method. Contemp Clin Dent 2012;
3: 388.
25 Swati C, Sonali S, Firoza S et al. Recent vs conven-
tional methods of caries removal: a comparative
in vivo study in pediatric patients. Int J Clin Pediatr
Dent 2015; 8: 6.
26 Matsumoto SF, Motta LJ, Alfaya TA et al. Assess-
ment of chemomechanical removal of carious
lesions using Papacarie Duo TM: randomized longitu-
dinal clinical trial. Indian J Dent Res 2013; 24: 488–
492.
27 Peters MC, Flamenbaum MH, Eboda NN, Feigal RJ,
Inglehart MR. Chemomechanical caries removal in
children: efficacy and efficiency. J Am Dent Assoc
2006; 137: 1658.
28 Goyal PA, Kumari R, Kannan VP, Madhu S. Efficacy
and tolerance of papain gel with conventional dril-
ling method: a clinico-microbiological study. J Clin
Pediatr Dent 2015; 39: 109–112.
29 Hamama HH, Yiu CK, Burrow MF, King NM. Sys-
tematic review and meta-analysis of randomized
clinical trials on chemomechanical caries removal.
Oper Dent 2015; 40: E167–E178.
30 Singh S, Singh DJ, Jaidka S, Somani R. Comparative
clinical evaluation of chemomechanical caries
removal agent papacarie â with conventional
method among rural population in india - in vivo
study. Braz J Oral Sci 2012; 10: 193–198.
31 Higgins J, Green S. Cochrane Handbook for Sys-
tematic Reviews of Interventions Version 5.1.0. Nau-
nyn-Schmiedebergs Archiv für experimentelle Pathologie
und Pharmakologie 2011;5: S38.
32 Tsesis I, Rosen E, Taschieri S et al. Outcomes of sur-
gical endodontic treatment performed by a modern
© 2018 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
technique: an updated meta-analysis of the litera-
ture. J Endod 2013; 39: 332–339.
33 Motta LJ, Bussadori SK, Campanelli AP et al. Pain
during removal of carious lesions in children: a ran-
domized controlled clinical trial. Int J Dent 2013;
2013: 896381.
34 Motta LJ, Bussadori SK, Campanelli AP et al. Ran-
domized controlled clinical trial of long-term
TM
chemo-mechanical caries removal using Papacarie
gel. J Appl Oral Sci 2014; 22: 307.
35 Motta LJ, Bussadori SK, Campanelli AP et al. Effi-
cacy of Papacarieâ in reduction of residual bacteria
in deciduous teeth: a randomized, controlled clinical
trial. Clinics (Sao Paulo) 2014; 69: 319–322.
36 Ammari MM, Moliterno LF, Hirata JR et al. Efficacy
of chemomechanical caries removal in reducing cari-
ogenic microbiota: a randomized clinical trial. Braz
Oral Res 1900; 28: 1–6.
37 El-Tekeya M, El-Habashy L, Mokhles N, El-Kimary
E. Effectiveness of 2 chemomechanical caries
removal methods on residual bacteria in dentin of
primary teeth. Pediatr Dent 2012; 34: 325.
38 Bohari MR, Chunawalla YK, Ahmed BM. Clinical
evaluation of caries removal in primary teeth using
conventional, chemomechanical and laser tech-
nique: an in vivo study. J Contemp Dent Pract 2012;
13: 40–47.
39 Kochhar GK, Srivastava N, Pandit IK, Gugnani N,
Gupta M. An evaluation of different caries removal
techniques in primary teeth: a comparitive clinical
study. J Clin Pediatr Dent 2011; 36: 5–9.
40 Kotb RM, Abdella AA, El Kateb MA, Ahmed AM.
Clinical evaluation of Papacarie in primary teeth. J
Clin Pediatr Dent 2009; 34: 117–123.
41 Lozano-Chourio MA, Zambrano O, Gonz
alez H,
Quero M. Clinical randomized controlled trial of
chemomechanical caries removal (CarisolvTM). Int J
Pediatr Dent 2010; 16: 161–167.
42 Maru VP, Kumar A, Badiyani BK et al. Behavioral
changes in preschoolers treated with/without rotary
instruments. J Int Soc Prev Community Dent 2014; 4:
77.
43 Maru VP, Shakuntala BS, Nagarathna C. Caries
removal by chemomechanical (CarisolvTM)vs.rotary
drill: a systematic review. Open Dent J 2015; 9: 462–472.
44 Divya G, Prasad MG, Vasa AAK et al. Evaluation of
the efficacy of caries removal using polymer bur,
stainless steel bur, carisolv, papacarie – an invitro
comparative study. J Clin Diagn Res 2015; 9: 42–46.
45 Motta LJ, Martins MD, Porta KP, Bussadori SK. Aes-
thetic restoration of deciduous anterior teeth after
removal of carious tissue with Papacarie. Indian J
Dent Res 2009; 20: 117.
46 Suzan S, Kumar VAA, Divya G et al. Effectiveness of
chemomechanical caries removal agents Papacar-
ieâand Carie-CareTM in primary molars: an in vitro
study. J Int Soc Prev Community Dent 2016; 6: 391.