Caries risk assessment using different Cariogram models. A comparative study about concordance in different populations-Adults and children.

This methodological survey aimed to verify whether there is concordance among several Cariogram different risk models at different thresholds, comparing both children and adult populations and how each risk/protective factor weight on the overall caries risk profile. Three groups' data (two in children and one in adults) were obtained from previous studies, while a fourth, in young adults, was ad hoc enrolled. Different caries risk levels were assessed: a) three risk categories with two different thresholds as: "low risk"  =  61-100% or 81-100% chance to avoid caries, "moderate risk"  =  41-60% or 21-80% and "high risk"  =  0-40% or 0-20%, named model 1 and 2; b) four risk categories with two different thresholds as: "low risk"  =  61-100% or 76-100%, "moderate/low risk" = 41-60% or 51-75%; "moderate/high risk" = 21-40% or 26-50% and "high risk" = 0-20% or 0-25%, model 3 and 4; c) five risk categories as: "very low risk"  =  81-100%; "low risk"  =  61-80% "moderate risk" = 41-60%; "high risk" = 21-40% and "very high risk" = 0-20%, model 5. Concordance of the different Cariogram risk categories among the four groups was calculated using Cohen's kappa. The weight of the association between all Cariogram models toward the Cariogram risk variables was evaluated by ordinal logistic regression models. Considering Cariogram model 1 and 2, Cohen's Kappa values ranged from 0.40 (SE = 0.07) for the young adult group to 0.71 (SE = 0.05) for the adult one. Cohen's Kappa values ranged from 0.14 (SE = 0.03 p<0.01) for the adult group to 0.62 (SE = 0.02) for the two groups of children in models 3 and 4. Statistically significant associations were found for all Cariogram risk variables excepting Fluoride program in models 4 and 5 and the overall risk on children's samples. Caries experience showed a quite variable weight in the different models in both adult groups. In the regression analyses, adult groups' convergence was not always achievable since variations in associations between caries risk and different risk variables were narrower compared to other samples. Significant differences in caries risk stratification using different thresholds stands out from data analysis; consequently, risk assessments need to be carefully considered due to the risk of misleadingly choosing preventive and research actions.

Introduction

Assessing and classifying individual caries risk is an essential step in the caries diagnosis and decision-making process. Caries risk assessment allows to achieve the best non-invasive and operative options, as well as establishing recall intervals [1, 2].

Caries Risk Assessment (CRA) should be an integral part of the treatment regimens, in order to plan an individualized caries prevention strategy. However, routinely the patient caries risk profile is not always determined and, when performed, the risk level is not always linked to the adopted preventive and intervention strategies [3, 4].

From the 2000s onwards, a variety of standardized tools were developed and tested in different populations [5, 6]. All multifactorial risk tools include a different combination of risk and protective factors, attributing to each variable a different weight in the caries risk calculation [7]. Despite this, the scientific evidence on CRA tools validity remains limited [5, 6, 8]. Overall, the Cariogram is the only multidimensional tool verified in children and adults in few good quality studies, even if its accuracy level was found to be limited in different age groups [5, 9]. Moreover, the Cariogram has been applied in different ways: considering seven to ten risk variables, considering three to five risk categories and finally, considering different thresholds to define each risk category [10-12]. These thresholds can lead to a loss of information because the entire range of predicted probabilities is not used, but also to substantial bias because the thresholds can occur as data-driven instead of pre-specified clinical data [9]. In particular, for risk assessment, an inappropriate use of a diagnostic tool can theoretically lead to both clinical and research bias. In fact, an underestimation or overestimation of the risk can lead to the choice of an inadequate preventive/therapeutic regime and/or to an incorrect enrolment of a subject in a study sample.

While the effectiveness of the Cariogram used with a reduced number of factors, mostly excluding salivary factors [13-17], has been validated, while the use of different risk categories considering different ranges of percentages to avoid caries was not investigated. In view of the foregoing, the present methodological study aimed, primary, to verify if there is concordance among the Cariogram caries risk categories at different thresholds in children and adults; and secondly, how much each risk/protective variable weight for the different overall caries risk profile in different age groups.

Material and methods

Samples

Four sample groups were considered in the comparisons. Two were obtained from previous studies in children (available at https://www.karger.com/Article/FullText/334932 and https://www.tandfonline.com/doi/full/10.1080/00016350902740498, respectively) [13, 16], one in adults (available at https://www.scielo.br/j/bor/a/ZqcrsmPRxNJQsYPV5nnNTTS/?lang=en) [17], and the fourth one, which included young adults, was ad hoc enrolled. Unlike the two groups of adults who are two distinct samples in which the risk assessment was carried out one time, the two samples of children are the same group of children whose caries risk was evaluated and re-evaluated after two years. Regarding the published papers [13, 16, 17], the abstracts can be easily retrieved on Pubmed.

Ethical issues were addressed as follows: the retrospective data analysis of archived samples the IRB of the University of Sassari waived the approval (IRB Sassari 20/04/2020); regarding the ad hoc sample the study proposal was accepted by the Ethical Committee of the University Hospital Milan (Comitato Etico Milano 1 n. 2019/ST/167).

All the surveys from which the data derives, were conducted by the same research group; in particular, two authors of the present survey acted as examiners/benchmarks in all surveys: MGC (Ayoung and Aold surveys) and GC (Cyoung and Cold surveys as examiner and Ayoung and Aold surveys as benchmark).

In children’s groups, a reduced Cariogram model (excluding saliva parameters: buffer capacity and saliva secretion rate) was build-up to assess the forecast probabilities of new caries. Two years later, the same sample was re-examined and the caries risk re-calculated. The children samples consisted of 957 subjects aged 7–9 years (Cyoung) and 862 children aged 9–11 years (Cold).

The adult sample (Aold) included 480 subjects aged 30–45 years. Caries risk was calculated through the full Cariogram model. For the last sample of young adults (Ayoung), undergraduate second and third-year dental students, School of Dentistry, University of Milan, Italy, were invited to participate. This convenience young adult sample consisted of 86 subjects (mean age 23.37 ± 3.11 years).

Data collection

Data for samples Cyoung, Cold and Aold, were extracted from the previously published studies. Data collection for sample Ayoung followed the same procedures in the adult population study [17], which included: a standardized high-structured self-administered questionnaire (in Italian and English language S1 and S2 Appendices) [18] collecting data on age, oral hygiene habits (frequency of toothbrushing), dietary habits (daily intake of sugary foods and drinks), fluoride exposure in addition to toothpaste and other remineralizing and antibacterial compounds, frequency of dental check-ups, presence of systemic diseases, and use of medications. Additionally, participants received clinical examinations by two examiners (GB and MGC) to determine caries prevalence at dentinal level, caries experience (Decayed, Missing and Filled Teeth index) [19] and plaque index [14]. The examiners were ad hoc calibrated on 15 subjects reporting a strong Cohen’s Kappa scores both for inter- and intra-examiner reliability (0.87/0.89 for inter-examiner and 0.85 for intra-examiner reliability) [20-22]. Finally, saliva chair-side tests were performed following the manufacturer’s instructions to evaluate the salivary oral streptococci and Lactobacillus spp. counts (CRT bacteria, Ivoclar Vivadent AG, Schaan, Liechtenstein), and buffer capacity (CRT Buffer, Ivoclar Vivadent AG, Schaan, Liechtenstein). The raw-data file was uploaded as S1 Data.

Risk assessment

Caries risk profiles were calculated using the Cariogram for all subjects in the different groups. Cariogram risk for samples Cyoung and Cold was calculated including seven risk/protective variables: caries experience, related diseases, diet content, diet frequency, plaque amount, oral streptococci count and fluoride program. For samples Ayoung and Aold, in addition to the previous factors, saliva secretion rate and buffer capacity were also included.

The caries risk level was assessed with five different models (Table 1): models 1 and 2—following three risk categories with two different thresholds (% chance of avoid caries) as: “low risk”  =  61–100% or 81–100%, “moderate risk”  =  41–60% or 21–80% and “high risk”  =  0–40% or 0–20%, respectively; models 3 and 4—following four risk categories with two different thresholds: “low risk”  =  61–100% or 76–100%, “moderate/low risk” = 41–60% or 51–75%; “moderate/high risk” = 21–40% or 26–50% and “high risk” = 0–20% or 0–25%, respectively; and finally, model 5—in five categories as follow: “very low risk”  =  81–100%; “low risk”  =  61–80% “moderate risk” = 41–60%; “high risk” = 21–40% and “very high risk” = 0–20% chance to avoid caries, respectively.

Table 1

Cariogram models and cutt-off values considered.

Cariogram	Risk levels (n)	Cut-offs (% of chances to avoid caries) and risk categories
		Low	Moderate	High
Model 1 a	3	61–100%	41–60%	0–40%
Model 2 b	3	81–100%	21–80%	0–20%
		Low	Low/Moderate	Moderate/High	High
Model 3 c	4	61–100%	41–60%	21–40%	0–20%
Model 4 d	4	76–100%	51–75%	26–50%	0–25%
		Very low	Low	Moderate	High	Very high
Model 5 e	5	81–100%	61–80%	41–60%	21–40%	0–20%

aPetsi G, Gizani S, Twetman S, Kavvadia K. Cariogram caries risk profiles in adolescent orthodontic patients with and without some salivary variables. Angle Orthod. 2014 Sep;84(5):891–5; Al Mulla AH, Kharsa SA, Kjellberg H, Birkhed D. Caries risk profiles in orthodontic patients at follow-up using Cariogram. Angle Orthod. 2009 Mar;79(2):323–30.

bZukanovic A. Caries risk assessment models in caries prediction. Acta Med Acad. 2013;42:198–208.

cChang J, Kim HY. Does caries risk assessment predict the incidence of caries for special needs patients requiring general anesthesia? Acta Odontol Scand. 2014;72:721–8; Petersson GH, Fure S, Bratthall D. Evaluation of a computer-based caries risk assessment program in an elderly group of individuals. Acta Odontol Scand. 2003;61:164–71.

dTwetman S, Petersson GH, Bratthall D. Caries risk assessment as a predictor of metabolic control in young Type 1 diabetics. Diabet Med. 2005;22:312–5.

eCampus G, Cagetti MG, Sale S, Carta G, Lingström P. Cariogram validity in schoolchildren: a two-year follow-up study. Caries Res. 2012;46:16–22; Petersson GH, Twetman S. Caries risk assessment in young adults: a 3 year validation of the Cariogram model. BMC oral health. 2015;15:17.

Statistical analysis

Cohen´s Kappa values were calculated to assess the agreement of the Cariogram risk categories among the 4 groups. Kappa statistics were tested using z test at a significance level of α = 0.01. Ordinal logistic regression models were built to evaluate the weight of the associations, via Odds Ratio and 95%Confidence Intervals, of the variables inserted on each Cariogram model toward Cariogram categorizations.

Results

Table 2 shows the demographic characteristics and caries figures of all groups. The mean caries experience (DMFT/dmft) ranged from 2.37±4.05 in the Cyoung (including both primary and permanent dentitions) to 3.25±4.15 in the Aold, with a D/d component ranging from 1.38±2.62 to 0.24±0.72, respectively.

Table 2

Description of the sample.

Samples	Cyoung	Cold	Ayoung	Aold
	n = 957	n = 862	n = 86	n = 480
Gender	Males n = 473 (49.37)	Males n = 421 (48.84%)	Males n = 39 (45.35%)	Males n = 254 (52.92%)
	Females n = 485 (50.63)	Females n = 441 (51.16%)	Females n = 47 (54.65%)	Females n = 226 (47.08%)
Age	6.49±0.71 years (range 7–9)	8.16±0.94 years (range 9–11)	23.37±3.11 years (range 21–27)	40.72±9.41 years (range 30–45)
Caries-free	409 (47.91%)	368 (42.69%)	26 (30.23%)	175 (36.46%)
Caries Experience	2.37±4.05 (range 0–19)	3.22±4.49 (range 0–23)	2.91±3.30 (0–13)	3.25±4.15 (0–21)
D/d	1.38±2.62 (range 0–17)	2.51±3.78 (range 0–22)	0.26±0.64 (range 0–3)	0.24±0.72 (0–8)
M/m	---	---	0.09±0.62 (range 0–5)	0.49±1.54 (0–9)
F/f	0.4±1.74 (range 0–7)	0.63±2.21 (range 0–10)	2.56±3.00 (range 0–11)	2.51±4.56 (0–20)

Comparisons among groups and the different risk categories and thresholds are displayed in Table 3. Caries risk profiles were statistically significant different for all age groups (p values ranging from <0.01 to 0.02) when considering three (low, moderate and high) and four (low, moderate/low, moderate/high and high) risk categories. Particularly, Cohen´s Kappa values ranged from 0.71 (SE = 0.05) to 0.40 (SE = 0.07) in the Aold and the Ayoung groups, respectively. Children groups showed intermediate values. On the other hand, when four risk categories were considered, Cohen´s Kappa values ranged from 0.62 (SE = 0.02) to 0.14 (SE = 0.03 p<0.01) in both children groups and in the Aold group. Comparisons for the last risk model (including 5 categories: very low, low, moderate, high, very high) were not performed since only one set of thresholds was used.

Table 3

Caries risk in the four samples using the five Cariogram models.

Model 1 (3 Risk categories)
	C young	C old	A young	A old
Low	487 (50.94)	449 (52.09)	55 (63.95)	12 (2.50)
Moderate	195 (20.40)	165 (19.14)	20 (23.26)	386 (80.42)
High	274 (28.66)	248 (28.77)	32 (37.21)	82 (17.08)
Model 2 (3 Risk categories)
Low	332 (34.73)	309 (35.85)	32 (37.21)	--
Moderate	432 (45.19)	378 (43.85)	52 (60.47)	479 (99.79)
High	192 (20.08)	175 (20.30)	2 (2.33)	1 (0.21)
Cohen Kappa	K = 0.63 SE = 0.03 p<0.01	K = 0.63 SE = 0.02 p<0.01	K = 0.40 SE = 0.07 p<0.01	K = 0.71 SE = 0.05 p = 0.02
Model 3 (4 Risk categories)
	C young	C old	A young	A old
Low	487 (50.94)	449 (52.09)	55 (63.95)	12 (2.50)
Low/Moderate	195 (20.40)	165 (19.14)	20 (23.26)	386 (80.42)
Moderate/High	82 (8.58)	73 (8.47)	9 (10.47)	81 (16.88)
High	192 (20.08)	175 (20.30)	2 (2.33)	1 (0.21)
Model 4 (4 Risk categories)
Low	332 (34.73)	309 (35.85)	37 (43.02)	--
Low/Moderate	249 (26.05)	213 (24.71)	29 (33.72)	152 (31.67)
Moderate/High	183 (19.14)	165 (19.14)	15 (17.44)	326 (67.92)
High	192 (20.08)	175 (20.30)	5 (5.81)	2 (0.42)
Cohen Kappa	K = 0.62 SE = 0.02 p<0.01	K = 0.62 SE = 0.02 p<0.01	K = 0.44 SE = 0.07 p<0.01	K = 0.14 SE = 0.03 p<0.01
Model 5 (5 Risk categories)
	C young	C old	A young	A old
Very Low	332 (34.73)	309 (35.85)	55 (63.95)	--
Low	155 (16.21)	140 (16.24)	20 (23.26)	12 (2.50)
Moderate	195 (20.40)	165 (19.14)	--__	386 (80.42)
High	82 (8.58)	73 (8.47)	9 (10.47)	81 (16.88)
Very High	192 (20.08)	175 (20.30)	2 (2.33)	1 (0.21)

A multinomial regression analysis was run, using caries risk categories as dependent variables, to evaluate the weight of the association (OR) between the overall risk measured with the different models and the risk/protective variables considered in each model (Table 4). In the Cyoung and Cold groups all considered risk variables were significantly associated to the caries risk profiles, except for fluoride program in models 4 and 5. However, each OR values ranged widely among models. While the weight of caries experience, oral streptococci and fluoride program remained quite stable in different models, diet content, diet frequency and plaque amount showed the widest variability in the weight of the associations. In Cyoung, diet content ranged from OR 2.48 95%CI 1.30 / 4.74 to OR 22.09 95%CI 6.23 / 78.34 in model 5 and 2, respectively; and plaque amount from OR 2.24 95%CI 1.53 / 3.28 to OR 299.53 95%CI 106.26 / 844.38 in model 1 and 2, respectively. Diet frequency for Cold exhibited the highest value in model 1 (OR 16.06 95%CI 1.94 / 13.15) and the lowest in model 4 (OR 4.54 95%CI 1.90 / 10.86), while plaque amount showed the highest value in model 2 (OR 405.56 95%CI 143.68 / 1144.80) and the lowest in model 1 (OR 1.55 95%CI 1.01 / 2.36). In relation to Ayoung group, caries experience showed a quite variable weight in the different models, reaching the highest value in model 3 (OR 32.49 95%CI 4.00 / 263.85), and the lowest in model 4 (OR 2.66 95%CI 1.56 / 4.52). All other risk variables resulted more strongly associated with risk profiles measured using model 1, with oral streptococci count and fluoride program showing the widest variations among models. Finally, given the low variance across risk variables and the reduced number of subjects in some risk categories, in the Aold group for models 2 and 4, the regression analysis was only achieved for model 1, 3 and 5. In this group, variation in weight between caries risk and different risk variables were narrower less broad compared to the above described samples. Fluoride program reached the highest OR in model 1 (3.16 95%CI 1.45 / 6.91) and buffer capacity in model 3 and 5 (OR 7.28 95%CI 0.90 / 34.62, in both models).

Table 4

Multinomial regression analysis.

Cariogram risk categories as dependent variables.

Cyoung Group
Risk variables	Model 1OR (SE) 95%CI	Model 2OR (SE) 95%CI	Model 3OR (SE) 95%CI	Model 4OR (SE) 95%CI	Model 5OR (SE) 95%CI
Caries experience	1.51(0.06) 1.40 / 1.63	1.53 (0.07) 1.39 / 1.67	1.40 (0.05) 1.31 / 1.49	1.72 (0.07) 1.58 / 1.87	1.59 (0.06) 1.49 / 1.70
Related disease	--	--	--	--	--
Diet contents	7.49 (5.03) 2.01 / 27.93	22.09 (14.27) 6.23 / 78.34	7.55 (5.10) 2.01 / 28.36	9.27 (3.91) 4.05 / 21.18	2.48 (0.82) 1.30 / 4.74
Diet frequency	2.85 (0.38) 2.20 / 3.70	2.73 (0.46) 1.96 /3.80	3.17 (0.43) 2.43 / 4.13	2.99 (0.40) 2.29 / 3.87	2.67 (0.31) 2.12 / 3.36
Plaque amounts	2.24 (0.44) 1.53 / 3.28	299.53 (158.39) 106.26 / 844.38	6.13 (1.14) 4.26 / 8.83	127.92 (38.26) 71.17 / 229.90	11.71(2.00) 8.38 / 16.37
Mutans streptococci	2.32 (0.15) 2.05 / 2.62	2.71 (0.24) 2.28 / 3.22	2.32 (0.13) 2.07 / 2.61	3.02 (0.23) 2.60 / 3.50	2.43 (0.141) 2.18 / 2.73
Fluoride program	1.78 (0.09) 1.58 / 2.06	1.84 (0.08) 1.61 / 2.24	1.48 (0.04) 1.15 / 2.02	1.25 (0.05) 0.94 / 1.54	1.25 (0.05) 0.94 / 1.54
Cold Group
Risk variables	Model 1OR (SE) 95%CI	Model 2OR (SE) 95%CI	Model 3 OR (SE) ( 95% CI)	Model 4OR (SE) 95%CI	Model 5OR (SE) 95%CI
Caries experience	1.69 (0.09) 1.52 / 1.87	1.50 (0.08) 1.36 / 1.66	1.43 (0.05) 1.33 / 1.54	1.81 1.64 / 2.00	1.63 (0.06) 1.51 / 1.76
Related disease	--	--	--	--	--
Diet contents	3.25 (0.48) 2.43 / 4.35	3.27 (0.61) 2.27 / 4.70	3.84 (0.58) 2.85 / 5.17	3.23 (0.46) 2.43 / 4.28	3.20 (0.41) 2.49 / 4.12
Diet frequency	16.06 (17.33) 1.94 / 13.15	9.02 (6.00) 2.45 / 33.21	11.40 (12.23) 1.39 / 93.33	4.54 (2.02) 1.90 / 10.86	1.40 (0.49) 0.70 / 2.80
Plaque amounts	1.55 (0.33) 1.01 / 2.36	405.56 (214.73) 143.68 / 1144.80	5.51 (1.11) 3.71 / 8.17	127.19 (39.15) 69.58 / 232.50	12.27 (2.24) 8.57 / 17.56
Mutans streptococci	2.42 (0.17) 2.11 / 2.79	2.60 (0.24) 2.18 / 3.12	2.27 (0.14) 2.0 / 2.56	3.00 (0.24) 2.57 / 3.50	2.39 (0.14) 2.12 / 2.67
Fluoride program	2.03 (0.12) 1.71 / 2.82	1.43 (0.03) 0.95 / 1.95	1.73 (0.04) 0.88 / 2.70	2.01 (0.05) 1.09 / 3.10	2.03 (0.05) 1.11 / 3.26
Ayoung Group
Risk variables	Model 1OR (SE) 95%CI	Model 2OR (SE) P-value 95%CI	Model 3 OR (SE) P-value ( 95% CI)	Model 4OR (SE) 95%CI	Model 5OR (SE) 95%CI
Caries experience	17.60 (20.74) 3.17 / 34.66	5.83 (2.85) 2.23 / 15.18	32.49 (34.72) 4.00 / 263.85	2.66 (0.719) 1.56 / 4.52	10.45 (4.68) 4.35 / 25.13
Related disease	--	--	--	--	--
Diet contents	38.66 (55.28) 2.35 / 637.47	4.36 (2.33) 0.53 / 12.45	16.911 (16.30) 2.69 / 111.90	5.83 (2.26) 2.73 / 12.45	8.24 (3.86) 3.29 / 20.64
Diet frequency	35.13 (45.94) 2.71 / 455.92	3.66 (1.72) 1.45 / 9.20	8.44 (5.65) 2.27 / 31.34	3.32 (1.08) 1.76 / 6.27	5.18 (1.96) 2.46 / 10.88
Plaque amounts	55.69 (106.22) 1.32 / 339.80	1.81 (1.77) 0.26 / 12.37	22.90 (34.84) 1.162 / 451.47	2.70 (2.02) 0.63 / 11.68	3.35 (2.56) 0.74 / 15.04
Mutans streptococci	238.38 (429.67) 6.97 / 815.87	4.57 (2.30) 1.71 / 12.25	81.96 (100.84) 7.35 / 913.92	4.47 (1.70) 2.12 / 9.44	10.38 (5.17) 3.91 / 27.56
Fluoride program	126.60 (41.07) 11.07 / 3388.01	23.45 (21.48) 3.89 / 141.14	97.64 (182.57) 16.56 / 553.66	11.15 (5.77) 4.04 / 30.76	85.99 (71.36) 16.90 / 437.35
Saliva secretion	75.71 (22.75) 3.15 / 181.69	4.17 (0.91) 1.01 / 16.40	11.78 (1.37) 2.10 / 26.13	3.12 (1.40) 1.30 / 7.52	7.39 (3.85) 2.67 / 20.44
Buffer capacity	36.08 (60.46) 1.35 / 96.29	3.94 (1.60) 0.73 / 21.03	5.55 (1.29) 0.87 / 35.77	5.84 (2.76) 1.67 / 20.46	8.07 (5.50) 2.12 / 30.74
Aold Group
Risk variables	Model 1OR (SE) 95%CI	Model 2OR (SE) 95%CI	Model 3OR (SE) 95%CI	Model 4OR (SE) 95%CI	Model 5OR (SE) 95%CI
Caries experience	3.61 (2.06) 1.18 / 11.03	convergence not achieved	2.51 (0.92) 1.22 / 5.14	convergence not achieved	2.51 (0.92) 1.22 / 5.14
Related disease	omitted		omitted		omitted
Diet contents	5.89 (2.54) 2.52 / 13.72		5.81 (2.32) 2.5 / 12.73		5.81 (2.32) 2.5 / 12.73
Diet frequency	4.16 (1.54) 1.36 / 10.22		3.76 (1.82) 1.44 / 9.72		3.76 (1.82) 1.44 / 9.72
Plaque amounts	3.00 1.60) 1.52 / 10.12		2.34 (0.62) 0.88 / 4.05		1.51 (0.84) 0,90 / 2.13
Mutans streptococci	6.81 (3.56) 2.44 / 18.94		5.29 (2.00) 2.52 / 11.13		5.29 (2.00) 2.52 / 11.13
Fluoride Program	3.16 (1.26) 1.45 / 6.91		0.77 (0.86) 0.08 / 6.82		0.77 (0.86) 0.08 / 6.82
Saliva secretion	3.46 (0.64) 0.71 / 6.48		2.51 (0.75) 1.00 / 6.08		2.51 (0.75) 1.00 / 6.08
Buffer capacity	3.82 (1.14) 0.81 / 4.72		7.28 (1.34) 0.90 / 34.62		7.28 (1.34) 0.90 / 34.62

Discussion

This study was designed to evaluate the concordance among caries risk profiles evaluated with Cariogram at different risk categories and different thresholds. The study used previous published data (two samples of schoolchildren and one of adults) and original data from a fourth group of young adults. The significant difference in caries risk stratification using different thresholds stands out as the main outcome of the present study.

The Cariogram demonstrates the caries risk graphically and provides a percentage value illustrating the probability an individual has to avoid the development of lesions in the near future. Nevertheless, the weights attributed to the risk factors considered in the Cariogram did not appear to explain caries experience or caries activity in all groups [23].

When assessing the caries risk what is expected to forecast is the chance to develop or not the disease and, in this perspective, only the subsequent incidence of “true” caries can confirm or disprove the initial hypothesis. The Cariogram was initially tested in children considering five risk categories [10]. Afterwards, its validity was demonstrated in elderlies and adults using different Cariogram models [24, 25]. Lack of calibration is a common problem of the Cariogram software, as the predictive capacity developed using data from a certain population can decrease when the tool is applied to another population. In these conditions, a recalibration can improve predictive capacity [6].

From a public health perspective, when caries risk is assessed in population samples, it is useful to allocate each subject into a risk category, facilitating the implementation of large-scale preventive and management interventions. However, the need to allocate subjects into risk categories for community purposes, as emerges from the findings of the present methodological study, can lead to risk category allocation biases due to the number of risk categories assessed and, above all, to the thresholds used to define each category. The allocation biases were perceived for all considered age groups. It is likely that different groups with different caries prevalence and risk variables could lead to different results. The present study findings might serve as a warning to public health dentists, epidemiologists and researchers on the adoption of the Cariogram models with different thresholds may lead to bias and an incorrect interpretation of the subject’s real risk. As suggested in the original Cariogram manual, [26, 27] low caries risk is only determined when the “Chance to avoid cavities” is equal to 75% or higher, while a high caries risk is plausible when the ‘Chance to avoid cavities’ is equal to 25% or lower. No suggestion is given for intermediate values. Nevertheless, in one of the earliest papers published on Cariogram, five risk categories were used (model 5 in the present paper) [27].

From a community or research perspective, an erroneous risk categorization could lead to unnecessary or inadequate preventive interventions [5]. This bias is confirmed by the analysis of the weight of the association between the risk/protective variables and the overall caries risk evaluated through the different five Cariogram models. The background risk factors (i.e. related disease, diet content, diet frequency, plaque amounts, oral streptococci, fluoride program, saliva secretion, buffer capacity) had a very different association with the caries risk measured with each model. Hence, the association between the caries risk and the background variables might be miscalculated and misunderstood. For example, the variable plaque amount assumes within the same sample an extremely high weight in some models and a reduced one in others. Also, the role of fluoride program is emblematic; it is not even associated to caries risk in some models (both in children and adults), while strongly associated in some of the adult models, and becomes weaker in others.

On the one hand, the Cariogram assessment at the individual level, allows to graphically evaluate which factors are the heaviest contributors to an individual caries risk, allowing to intervene on them. On the other hand, as previously reported, the graphical advantages of the Cariogram are practically unattainable at a community level, leading to non-effective interventions from a clinical and/or cost / benefit point of view [28, 29].

A major limitation of the present paper is undeniably the small number of participants in the sample Ayoung. The small number of participants is unfortunately related to the historical moment, COVID-19 pandemic, in which the study was carried out. As the lockdown was declared by the Italian Government, the study was halted with the hope to resume in September; unfortunately, the conditions related to the pandemic made it impossible, resulting so in a small sample size. Although with this factual limitation, the authors believe that the sample can provide proper support in the paper. In this sample, caries experience showed a quite variable weight in the different models, reaching the highest value in model 3, allowing some generalisation of the results.

Some strengths have to be considered. First of all, this is the first study that compares different models of the Cariogram in different populations. In fact, it is known that the tool does not work as well in all population groups [5, 9]. Furthermore, the fact of having tested different models both in samples of children and adults of different ages gives value to the results of this comparative paper. Finally, having assessed for each model and in each population group the strength of association of each risk factor with the overall caries risk, is a new and little explored aspect that has allowed to verify how much each factor play a different role in the different models and samples.

Conclusions

The outcomes of this study might allow to conclude that the caries risk assessment is modified when the Cariogram thresholds vary. The interpretation of caries risk profiles needs to be carefully considered in dental public health, given the risk of misleading the choice of both preventive and management actions, as well as the wrong selection of subjects in specific caries risk categories for research purposes.

STROBE statement—checklist of items that should be included in reports of cross-sectional studies.

(DOC)

Click here for additional data file.

(DOC)

Click here for additional data file.

(DOC)

Click here for additional data file.

(XLSX)

Click here for additional data file.

2 Nov 2021

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Denis Bourgeois

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf.

2. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information.

3. We noted in your submission details that a portion of your manuscript may have been presented or published elsewhere. [As it was described in the manuscript (Materials and Methods pages 5-6), Four sample groups were considered in the comparisons. Two were obtained from previous studies in children [11, 14], one in adults [15], and the fourth one, which included young adults, was ad hoc enrolled.] Please clarify whether this [conference proceeding or publication] was peer-reviewed and formally published. If this work was previously peer-reviewed and published, in the cover letter please provide the reason that this work does not constitute dual publication and should be included in the current manuscript.

4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I have reviewed the paper “Caries risk assessment using different Cariogram models. A comparative study about concordance in different populations - adults and children.”

When assessing caries risk what is expected to forecast is the chance to develop or not the decease. In this sense it would be useful to compare the different models against true caries increment. One would expect that change of cut off points in the Cariogram will end up in different results. Therefore comparing different models between them does not have a clinically meaningful conclusion.

Cariogram weights the different factors using an internal algorithm and produces the outcome. Trying to separate the factors in a regression analysis to identify which correlates with caries risk does not make sense because this has been done by the program. Again, there is no clinically meaningful conclusion for the aim of the study

The introduction does not justify the aim of the study, as literature more relevant to the paper has not been mentioned and the discussion is poor. Regarding the methodology it is not clear why the specific age groups where chosen and if clinical examination was similar to all participants.

Reviewer #2: The reviewed paper is a methodological survey to verify whether there is concordance among several Cariogram risk assessments at different cut-off values, comparing both children and adult populations; and how each risk/protective factor weights on the overall caries risk profile.

For this purpose, a total of three groups' data (two in children and one in adults) were obtained from previous studies, while a fourth, in young adults, was enrolled ad hoc.

The results were significant differences in caries risk stratification using different cut-offs stands out from data analysis; consequently, risk assessments need to be carefully considered due to the risk of misleadingly choosing preventive and research actions.

This is a well-written paper worth publishing in Plos One. However, some points should be addressed:

1. check capitalization -> e.g. keywords or table description table 1.

2. it is not clear whether only the children groups were re-examined and the caries risk recalculated years later or was this re-examined and recalculated for all groups included in the study two years later?

3. the groups are very different in size, especially the sample that was added ad hoc. Even if it is designed for clarity with division young/old children/adults very clearly for the reader, percentages of a sample below 100 are rather strange to read with percentages. Would it not be possible at this point to enlarge this group so that there are not exorbitantly large differences (957, 862, 86, 480)?

4. are there numerous spelling mistakes, e.g. in table 2 the absolute number is missing for caries-free in Aold (n=480) before (36.46%), p. 10 "25% or lower. .", p. 11 "interpretadtion", table description of Table 1, etc.

5. no information on the validation of the questionnaire is given.

6. no information about the training and calibration of the two examiners is given.

7. there is no information about the saliva chair-side test used, e.g. manufacturer, etc.

8. what are the standardized conditions under which the saliva test was used?

9. the correct wording and spelling of the bacteria should be followed.

10. awkward wording "Nevertheless, some of the original Cariogram authors suggested, in one of the earliest papers published on Cariogram, the use of five risk categories) should be reworded.

11) "Plaque amount" is a perfect example of this;" should be reworded.

Reviewer #3: Dear authors,

The study has several significant drawbacks.

The references are outdated.

Only four references are from the last five years. It may help if they find more recent articles as I suggested in a comment in the Introduction.

The conclusion need be more in line with the aim of the research (for abstract and the whole manuscript).

There are recent articles that use different cut-offs to define risk category according to Cariogram. Also, some studies use sensitivity, specificity, positive and negative predictive values according to Youden's index. It is necessary to look for them and expand this part (the Background – part where you mention references 8-10 - in attached documents) with these references, as well as the Discussion part. Taken as a whole, the references from the entire paper are older. Only four references are from the last five years.

The discussion is very brief. The authors compare their results and conclusions with only four references, and one is newer. It seems that they have not considered recent findings of the use of Cariogram.

- What are the strengths of your study?

- Please mention the limitations of your study.

- The authors need to systematically compare their findings with previous studies and provide logical justification for any reported differences.

It may help if they find more recent studies and compare with them as I suggested in comment in the Background.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Submitted filename: PONE-D-21-19761_reviewer.pdf

Click here for additional data file.

14 Feb 2022

First, we really want to express our gratitude to the Editor and the reviewers for the help provide to us to improve the quality of our paper.

Below all the suggestions form Journal requirements and reviewers (in bold) and our replies (in italics)

Journal Requirements:

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf.

Done.

2. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information.

We included as supplementary file the questionnaire in English.

3. We noted in your submission details that a portion of your manuscript may have been presented or published elsewhere. [As it was described in the manuscript (Materials and Methods pages 5-6), Four sample groups were considered in the comparisons. Two were obtained from previous studies in children [11, 14], one in adults [15], and the fourth one, which included young adults, was ad hoc enrolled.] Please clarify whether this [conference proceeding or publication] was peer-reviewed and formally published. If this work was previously peer-reviewed and published, in the cover letter please provide the reason that this work does not constitute dual publication and should be included in the current manuscript.

Three of the four samples used in this study in order to compare the risk assessment through different Cariogram models have already been the object of study of previous published papers. In this study, the different parameters relating to caries previously collected, were re-evaluated to calculate the risk profiles considering different cutoffs to define each risk categories. As consequence, present findings do not represent a duplicate of what has already been published.

4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

Done

Reviewer #1:

1. When assessing caries risk what is expected to forecast is the chance to develop or not the disease. In this sense it would be useful to compare the different models against true caries increment. One would expect that change of cut off points in the Cariogram will end up in different results. Therefore, comparing different models between them does not have a clinically meaningful conclusion.

We disagree with the reviewer’s comment. The caries incidence is the only outcome that can establish with certainty if the previous risk assessment was correct. However, in this paper the goal was to verify how, in different samples, the use of different Cariogram models could give the clinician not congruent information. Although all the models tested have been used successfully in the literature, the results of the present evaluation highlight that caution should be used when different cut-offs than those originally proposed by Cariogram’s authors, are used. This does not mean that other models than the original should definitely not be used but that a "calibration" of the model on your each single sample should be performed as suggested in Trottini M, Campus G, Corridore D, Cocco F, Cagetti MG, Vigo MI, Polimeni A, Bossù M. Assessing the Predictive Performance of Probabilistic Caries Risk Assessment Models: The Importance of Calibration. Caries Res. 2020;54(3):258-265..

2. Cariogram weights the different factors using an internal algorithm and produces the outcome. Trying to separate the factors in a regression analysis to identify which correlates with caries risk does not make sense because this has been done by the program. Again, there is no clinically meaningful conclusion for the aim of the study.

We disagree with the reviewer’s comment. The internal algorithm weight the different the different factors in a prefixed model, but each population is different and also the weight of the different risk factors in relation to caries increment. We really believe that knowing the weight of the different risk factors on caries increment has a quite important clinical implications especially planning preventive programs in population with skewed caries figures. We will try to explain this in the manuscript.

3. The introduction does not justify the aim of the study, as literature more relevant to the paper has not been mentioned and the discussion is poor.

The introduction was modified following the recommendations of the reviewer

4. Regarding the methodology it is not clear why the specific age groups were chosen and if clinical examination was similar to all participants.

We described in the Methodology section this. The clinical examinations were carried out from examiners of the same research group. The research group has an has decades of experience in designing and conducting epidemiological research documented by dozens of scientific publications, some of which focused on methods for calibrating and standardizing examiners for this type of survey. In particular, two authors of the present survey acted as examiners/benchmarks in all surveys: MGC (Ayoung and Aold surveys) and GC (Cyoung and Cold surveys as examiner and Ayoung and Aold as benchmark). We add some clarification in the materials and methods sections.

Reviewer #2:

1. Check capitalization -> e.g. keywords or table description table 1.

Capitalization was checked and modified when necessary

2. it is not clear whether only the children groups were re-examined and the caries risk recalculated years later or was this re-examined and recalculated for all groups included in the study two years later?

As suggested by the reviewer this point was clarified. The following sentence was added to Material and Methods (Sample) “Unlike the two groups of adults who are two distinct samples, the two samples of children are actually the same group whose caries risk was evaluated and re-evaluated two years later”

3. the groups are very different in size, especially the sample that was added ad hoc. Even if it is designed for clarity with division young/old children/adults very clearly for the reader, percentages of a sample below 100 are rather strange to read with percentages. Would it not be possible at this point to enlarge this group so that there are not exorbitantly large differences (957, 862, 86, 480)?

The referee's comment hits a very important spot. when we designed the addition of this sample (Ayoung) we had assumed a higher sample. Unfortunately, running the study, the COVID-19 pandemic arrived. The population enrolled in the study were University students in the city of Milan. In April, 2020 the first lockdown was declared, and all university classes went online.

We therefore had to interrupt the study, planning to resume in September; unfortunately, the conditions related to the pandemic forced the academic authorities to keep classes online only.

We are fully aware that this is a major weakness of our study. We decided to add a paragraph about this in the discussion section.

4. are there numerous spelling mistakes, e.g. in table 2 the absolute number is missing for caries-free in Aold (n=480) before (36.46%), p. 10 "25% or lower. .", p. 11 "interpretadtion", table description of Table 1, etc.

We are sorry for this. Spelling mistakes were corrected

5. no information on the validation of the questionnaire is given.

The information about the validation and standardization of the questionnaire was added as a reference.

6. no information about the training and calibration of the two examiners is given.

The information about the examiners’ calibration was added.

7. there is no information about the saliva chair-side test used, e.g. manufacturer, etc.

The information was reported

8. what are the standardized conditions under which the saliva test was used?

“Standardized conditions” was replaced by “following the manufacturer’s instructions”

9. the correct wording and spelling of the bacteria should be followed.

Bacteria names were corrected

10. awkward wording "Nevertheless, some of the original Cariogram authors suggested, in one of the earliest papers published on Cariogram, the use of five risk categories) should be reworded.

The sentence was reformulated as follow: “In one of the earliest papers published on Cariogram, five risk categories were used (model 5 in the present paper)”

11. "Plaque amount" is a perfect example of this;" should be reworded.

The sentence was reformulated,

Reviewer #3:

1. The references are outdated. Only four references are from the last five years. It may help if they find more recent articles as I suggested in a comment in the Introduction.

We updated the reference of this, even if the papers about the development of the software has to be cited.

2. The conclusion need be more in line with the aim of the research (for abstract and the whole manuscript).

We modified the conclusion following the reviewer’s suggestion.

3. There are recent articles that use different cut-offs to define risk category according to Cariogram. Also, some studies use sensitivity, specificity, positive and negative predictive values according to Youden's index. It is necessary to look for them and expand this part (the Background – part where you mention references 8-10 - in attached documents) with these references, as well as the Discussion part. Taken as a whole, the references from the entire paper are older. Only four references are from the last five years.

As described above we updated the references and modified both the introduction and the discussion section following the reviewer’s suggestions.

4. The discussion is very brief. The authors compare their results and conclusions with only four references, and one is newer. It seems that they have not considered recent findings of the use of Cariogram. What are the strengths of your study?

A deep re-writing of the discussion section was performed. We also include the strengths of the study.

5. Please mention the limitations of your study.

We mentioned the limitation of our study in the discussion section.

6. The authors need to systematically compare their findings with previous studies and provide logical justification for any reported differences. It may help if they find more recent studies and compare with them as I suggested in comment in the Background.

We followed the reviewer’s suggestions and we deeply modified both the introduction and the discussion sections including the limitations of the study and comparing the findings with previous publications.

Submitted filename: Replay to reviewers.docx

Click here for additional data file.

21 Feb 2022

Caries risk assessment using different Cariogram models. A comparative study about concordance in different populations - adults and children.

PONE-D-21-19761R1

Dear Dr. Campus,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Denis Bourgeois

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: (No Response)

Reviewer #3: The authors corrected the article according to the reviewer's suggestions.

The paper can be accepted for publication.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: No

16 Jun 2022

PONE-D-21-19761R1

Caries risk assessment using different Cariogram models. A comparative study about concordance in different populations - adults and children.

Dear Dr. Campus:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Professor Denis Bourgeois

Academic Editor

PLOS ONE