Evidence-Based Practice for the Use of pH Indicator Paper Strip in Oral Medicine: A Literature Review

The objective of our article is to review the literature and collect the advice of specialists for the evaluation of the reliabilityand appropriate indications of the use of pH paper in oral medicine practice. The literature pertaining to the use of pH paper in oral medicine practice was reviewed, and appropriate indications were suggested by a French multidisciplinary working group of specialists and validated by a lecture committee. By screening PubMed/MEDLINE from 1911 to March 2024, we found 621 articles. All abstracts were read, 22 articles were selected for full-text reading, and 12 were ultimately included in the review. Three more articles from other sources were included. Thus, 15 articles constituted the literature review; seven papers from PubMed/MEDLINE focusing on how to restore the salivary pH balance in cases of periodontitis and early childhood caries (ECC) completed the review. It is concluded that the lack of sensitivity of pH paper must be underlined. A low pH is a cofactor leading to oral pathologies, and the use of pH paper constitutes an easy diagnostic instrument in patients with pH variations correlated to leukemia, diabetic mellitus, or orofacial radiotherapy. The evaluation of salivary pH using pH paper may be used as a quick chairside test, specifically in cases of ECC and uncontrolled severe periodontitis. Early diagnosis of salivary low pH range in children as well as periodontitis with deep pocket associated with a low pH range in adults should lead to the supply of fluoride and prescript sodium bicarbonate-containing dentifrices, respectively. In children, the use of a chewable toothbrush may help reduce plaque and elevate salivary pH.


Introduction And Background
The pH scale is logarithmic and inversely indicates the activity of hydrogen ions in a solution.The salivary pH may be correlated to the oral and general health status, such as neurological or oral motor dysfunction [1,2].Salivary components may suffer variations that can be detected by chemical determinations.Low pH levels have been correlated with dental caries prevalence in young diabetics, according to López et al. [2,3].In periodontitis, Galgut [4] established a highly significant correlation between the periodontal pocket and pH range and a significant correlation between the deep pocket and low pH range.
The use of pH paper seems to have been partially abandoned in oral medicine clinical practice.Nowadays, the use of electrodes in oral investigations has been strongly developed.A measurement by paper strip has been developed as an assessment tool that is noninvasive, painless, easily collected, and, in general, less expensive than other diagnostic tools.These small strips of paper are coated with a special dye that changes color when it comes into contact with acidic or basic substances.The aim of this review is to evaluate the reliability and indications of the use of pH indicator paper strips in oral health and medical status.

Review Preliminary search
The literature review of the indications of pH paper use was performed by searching the PubMed/MEDLINE database.The screening included articles published between 1911 and March 2024 in French or English using the following keywords: ((Salivary pH) or (pH saliva) or (oral cavity pH)) and ((pH indicator strips) or (pH indicator paper)) and ((disease) or (pathology) or (treatment)).

Eligibility criteria
The case study, case report, and case series articles were selected for the review if they respected the following inclusion criteria: (a) measured the salivary pH; (b) used a pH indicator paper; (c) on patients with oral or systemic diseases or under pharmacological treatment.These criteria were applied with no restriction on the level of scientific evidence.Abstracts and full-text articles relating to the measurement of salivary pH with other techniques than pH paper and/or in patients without pathology or treatment were excluded.Studies in other languages than English or French were excluded.Further research using the references quoted in the full-text articles was carried out.A second screening of articles published between 1983 and 2022 focusing on how to restore the salivary pH balance -matching the following keywords: (periodontitis), (early childhood caries), and (sodium bicarbonate) -completed the literature review.

Data processing
The articles and guidelines were analyzed, and a first set of data was proposed for peer review by a working group (see Appendix A for members of the working group).The revised recommendations were then submitted to a multidisciplinary lecture committee (see Appendix A for members of the lecture committee).The final document was modified according to the multiple critical appraisals of the two groups.The literature review was followed by critical appraisal by a multidisciplinary working group in order to classify data according to the levels of scientific rigor (levels 1, 2, 3, and 4) [5].

Results
The study selection methodology is presented in Figure 1.

Method of Measurement
Of the 15 publications reviewed, 10 measured the salivary pH by first collecting the saliva in a container with a spitting or drooling method.Most of these studies (eight out of 10) collected unstimulated saliva (Table 1).In some studies, the collection of unstimulated saliva was done after at least one hour of fasting, with a water rinse before collection.Stimulated saliva was obtained after asking the patient to chew on a piece of parafilm for five minutes.It appears that the more recent studies used a method of placing the pH paper in the collected saliva rather than placing the pH paper (Figure 2) directly in the mouth of the patient (Figure 3).The majority of the studies measured unstimulated saliva which requires at least one hour of fasting.The brand of the pH contact varies widely from one study to another.

Indications of Salivary pH Indicator Paper Strip
In eight of the 15 articles, the studied populations were children.Five articles focused on diabetes.All studies on caries were carried out in children (

Head and Neck Cancer and Hematological Pathology
Ramya et al. [6] measured a lower pH for patients with cancer before or under treatment compared to healthy controls.A significant decrease in salivary pH for patients with cancer was also found, but this resulted from data measured by a pH meter; the results of the pH paper were not statistically analyzed.Moreover, it was not specified which cancer was involved, although we can assume they were head and neck cancers.
Cervicofacial radiotherapy is also reported to change the pH to be more acidic, as Laudenbach et al. [1] pointed out, but this publication did not perform statistical analysis.
Kapoor et al. [7] studied the pH of children with leukemia and found a significantly lower pH in the leukemia group as well as in the intensive treatment group compared to the maintenance treatment group.The children with leukemia had fewer caries compared with the controls.Dubey et al. [8] examined the salivary pH of patients with leukemia; the authors compared caries status using mean decayed, missing, and filled teeth (DMFT) indices with salivary pH.Results revealed that the mean deft/DFMT indices of children with leukemia were significantly higher than children with diabetes or asthma, meaning children with leukemia had poorer oral health.However, this study did not use healthy patients as a control and did not mention the salivary pH measured.In the oncological population, it appears that good oral hygiene is important in order to maintain the salivary pH in a healthy 7.0 mean range [6].

Diabetes
In Swapna et al.'s study [9], there was no statistically significant difference in salivary pH between the two groups of the patients' diabetics and nondiabetics under hemodialysis; there was a suggestive significance statistically, with a pH value of >7.0 being recorded among 34% nondiabetics and only 17% diabetic patients (p < 0.056).No correlation was analyzed with other oral manifestations or oral health.
A low pH in the case of diabetes was also described by Laudenbach et al. [1], with causes such as hyposialia or a tendency to ketonemia.
In the pediatric population, pH was measured at around 6.76 in diabetic patients by Díaz Rosas et al. [10], and they obtained a positive correlation between salivary flow and pH.Rai et al. [11] measured a significantly lower salivary pH in diabetic children compared to healthy children, as well as poorer oral hygiene, but no correlation was found between pH and oral health.

Periodontitis and Gingivitis
Diagnosis of periodontitis needs recording clinical factors: gingival health, pocket depths, bleeding on probing, furcation lesions, tooth mobility, and occlusion.Having recorded these factors, together with information on the patient's age and medical history, a provisional diagnosis can be made.Additional information may be obtained from a radiographic examination, a pulp vitality test, and microbiological and hematological investigations.Galgut [4] established a highly significant correlation between total pocket and pH range and a significant correlation between deep pocket and low pH range.No significant correlation between moderate pocket and pH, or between healthy sites, gingivitis, and pH.In this study, the pH varied widely from one measure to another, and the authors concluded that a more precise way of measuring pH was needed, but that the pH paper can be a useful technique for screening the disease activity in clinical practices.The knowledge of salivary pH levels helps justify the prescription of sodium bicarbonatecontaining solutions or dentifrices.
Laudenbach et al. [1] also reported an alkaline pH in the case of parodontitis, stomatitis, or other oral bacterial infections such as parotitis or sialodochitis.

Oral Health
The use of pH paper by the patients themselves in their hygiene routine showed a significant increase in their motivation to brush their teeth better and longer [12].pH paper can be a tool to increase the motivation of patients to take care of their oral health.
About caries in children, Aliakbarpour et al. [13] concluded that there was no significant difference in mean salivary pH between children with or without ECC.They mentioned the lack of sensitivity of pH paper and the possible error in reading the results as possible causes for this outcome.Muchandi et al. [14] found different results, with a pH significantly more acidic in children with severe ECC compared to caries-free children and a negative correlation between salivary pH and the total antioxidant capacity.

Orthodontic Treatment
Arendorf and Addy [15] found a significant fall in salivary pH during orthodontic appliance therapy and a significant rise after the appliance was removed.It was associated with a significant increase in the prevalence of candida carriage during the appliance treatment and a significant decrease after removal.

Taste Disorders
In their study, Walliczek-Dworschak et al. [16] did not find a significant difference in salivary pH between the patients and the controls.A significant correlation was established between pH and salivary flow rate, and patients showed a higher flow rate.

Gastroesophageal Reflux Disease (GERD)
Caruso et al. [17] found a significant decrease in salivary pH for patients with GERD.They concluded that a presumptive diagnosis of GERD can be made with a salivary pH ≤5 associated with a nasal pH ≥8.This implies that the method of measurement of the nasal pH must be known by the practitioner.
[18] found a pH significantly lower in children with β-thalassemia than in healthy controls.The study did not establish a correlation between pH acidity and dental health.

Reliability of Salivary pH Measurement Using pH Paper
The majority of the studies measured unstimulated saliva, which requires at least one hour of fasting.This is a limit for this method of pH measurement in consultations because it withdraws from the fast and practical side of the exam.The reliability of pH paper compared to a pH meter has also been examined for other biological fluids such as vaginal secretions [19] or aspirated gastric juice [20], and it was shown that pH determination by pH paper was reliable.Song et al. evaluated the reliability of salivary pH measurement using pH paper.They concluded that pH paper has sufficient reproducibility, especially for unstimulated saliva [21].
This suggests that pH paper can be used as a support for clinical examination, followed by a more precise evaluation if necessary.The pH paper test is a low-cost, noninvasive method that ensures an instantaneous result that is immediately visualized by the patient.Thus, the training of medical professionals will allow for accurately performing pH paper testing and interpreting results in the context of specific patient conditions.

Oral Medicine
The use of salivary pH in oral medicine as a tool in diagnostic and therapeutic assessment could be summarized as follows: ECC: pH paper may be used as a quick and noninvasive chairside test to assess salivary pH levels in young children (before five years old), particularly those at risk of ECC.Performing regular salivary pH testing during dental checkups allows for the identification of acidic conditions conducive to ECC development.
Oral lesions: Salivary buffering capacity depends on the amount of acid and bases present in the secreted saliva, and bicarbonate is the principal buffering agent.Bicarbonate secretion increases as the salivary flow rate increases.Foglio-Bonda et al. [22] found statistically significant decreased salivary flow rate and altered pH in patients with oral lesions when compared to patients without oral lesions.In their study, a decreased flow rate of 0.336 ml.min-1 and an increased pH of 6.69 were seen.
Gingivitis and periodontitis: Using pH papers as a rapid diagnostic tool to assess salivary pH in patients with uncontrolled severe (grades 3 and 4) periodontitis and implementing salivary pH testing as a supplementary measure to evaluate the oral environment and its impact on periodontal health status can be beneficial.Salivary pH analysis facilitates the discrimination between inflamed and healthy gingival tissues and provides a means to evaluate pH variations within periodontal pockets.Early diagnosis of salivary low pH range in children as well as periodontitis with deep pocket associated with a low pH range in adults should lead to the supply of an amount of fluoride and the prescription of sodium bicarbonate-containing dentifrices, respectively [23].In children, the use of a chewable toothbrush may help reduce plaque and elevate salivary pH [24].
Taste disorders: Salivary pH testing demonstrates limited discriminative ability between individuals with taste disorders and unaffected controls.

General Medicine
The use of salivary pH in general medicine as a tool in diagnostic and therapeutic assessment could be summarized as follows: Head and neck cancer patients: Salivary pH monitoring with pH strips presents potential utility in tracking radiotherapy-induced pH fluctuations among cancer patients both pre-and intra-treatment [6].
GERD patients: The utilization of salivary pH paper aids in discerning between GERD-afflicted individuals and controls by evaluating their mean salivary pH levels.The saliva pH, which under normal conditions varies between 7.0 and 7.2 in the presence of GERD, is affected by the influence of acidic gastric juice [17].
Diabetic patients undergoing hemodialysis and diabetic children: Assessment of salivary pH dynamics offers valuable insights into their oral health status [6,8].
β-thalassemia major: For patients with β-thalassemia major, salivary pH examination enables differentiation between β-thalassemia major cases and controls based on mean salivary pH levels; pH is significantly lower compared to the control group [18].
Leukemia: Salivary pH paper distinguishes between leukemia patients undergoing varied treatment modalities and their healthy counterparts [7].Results revealed lower pH mean values in children diagnosed with leukemia undergoing chemotherapy compared with healthy children without systemic disease.Moreover, a lower pH mean value was noticed in children with leukemia undergoing the intensive phase of chemotherapy compared with children with leukemia undergoing the maintenance phase of chemotherapy.

Conclusions
The lack of sensitivity of pH paper must be underlined.A low pH is a cofactor leading to oral pathologies, and the use of pH paper constitutes an easy diagnostic instrument in patients with pH variations correlated to leukemia, diabetic mellitus, or orofacial radiotherapy.The evaluation of salivary pH using pH paper may be used as a quick chairside test, specifically in cases of ECC and uncontrolled severe periodontitis.The knowledge of salivary pH level helps justify the prescription of fluoride, sodium bicarbonate-containing solution, or dentifrices, respectively.
into small pieces, placed interdentally in one healthy site, in one inflammatory site without pocketing, in one site with pocketing, on the floor of the mouth, and in the midline of the soft palate for 30 90) with cancer prior to treatment vs. patients with cancer undergoing treatment vs. healthy controls Two to three drops of unstimulated whole saliva on the strip; saliva collected by spitting five minutes after the water rinse and after at least an hour without drinking and eating = 97) with and without diabetes undergoing hemodialysis for more than a year Unstimulated whole saliva pooled on the top of the tongue by the patient, and a pH paper strip was placed 12-year-old type I diabetic children (n = 200) vs. healthy children pH tested on unstimulated saliva collected by passive drooling after two hours without eating adults (n = 21) in the prevention of oral health By licking a sampling pad on the test trip and folding it on the pH indicator pad, for one group; no measurement of pH for the other group pH range of 6.5-year-old children (n = 90) with ECC vs. children with severe ECC vs. caries-free children Unstimulated whole saliva collected after at least an hour without drinking and eating Merck17-year-old children (n = 33) with upper removable appliance orthodontic treatment Saliva pH was measured by placing pH paper on the tongue for one minute Whatman BDH pH indicator strips Level Walliczek-2024 Shamsi-Basha et al.Cureus 16(6): e62797.DOI 10.7759/cureus.81)with taste disorders vs. healthy controls Stimulated saliva spat out after chewing on a piece of paraffin for five minutes; pH measured on samples stored atstudy Patients (n = 20) with symptoms of GERD vs. healthy controls Unstimulated whole saliva collected after a fast and a water rinse Strip of pH 1six-year-old children (n = 68) with β-thalassemia major vs. healthy controls Unstimulated whole saliva collected after at least an hour without drinking and eating Merck, Germany Level 3

TABLE 1 : Overview of selected publications
[5]ierarchy of levels of scientific rigor[5]: level 1 (high level): RCTs with high statistical power, meta-analyses of RCTs, and decision analysis based on studies with high methodologic quality; level 2 (intermediate level): RCTs with low statistical power, nonrandomized comparative studies with high-quality methodology, and cohort studies; level 3 (weak level): case-control studies; level 4 (weak level): comparative studies with important bias, retrospective studies, sample of cases, and descriptive epidemiologic studies (cross-sectional or longitudinal).GERD, gastroesophageal reflux disease; RCT, randomized controlled trial

TABLE 2 : Relevance of pH to various pathologies
ECC, early childhood caries; GERD, gastroesophageal reflux disease