Keywords
Oro-facial pain, diagnostic accuracy, point-of-care testing, systematic review, pulpitis, temporomandibular disorders, periodontal disease, dental diagnostics
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Rai A, Mahuli SA, Mahuli AV et al. Diagnostic tests for oro-facial pain: protocol for a suite of systematic reviews and meta-analyses [version 1; peer review: awaiting peer review]. F1000Research 2025, 14:495 (https://doi.org/10.12688/f1000research.164451.1)
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Study Protocol
Diagnostic tests for oro-facial pain: protocol for a suite of systematic reviews and meta-analyses
[version 1; peer review: awaiting peer review]
PUBLISHED 14 May 2025
OPEN PEER REVIEW
REVIEWER STATUS
Abstract
Corresponding author:
Simpy Amit Mahuli
Competing interests:
No competing interests were disclosed.
Grant information:
This review is supported by the Centre for Evidence for Guidelines, Indian Council of Medical Research (ICMR), Department of Health Research (DHR), Ministry of Health and Family Welfare, Government of India, New Delhi, India
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Copyright:
© 2025 Rai A et al.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
How to cite: Rai A, Mahuli SA, Mahuli AV et al. Diagnostic tests for oro-facial pain: protocol for a suite of systematic reviews and meta-analyses [version 1; peer review: awaiting peer review]. F1000Research 2025, 14:495 (https://doi.org/10.12688/f1000research.164451.1)
First published: 14 May 2025, 14:495 (https://doi.org/10.12688/f1000research.164451.1)
Latest published: 14 May 2025, 14:495 (https://doi.org/10.12688/f1000research.164451.1)
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Introduction
Oro-facial pain is a prevalent clinical challenge with a wide spectrum of etiologies, including pulpal and periapical pathology, periodontal disease, temporomandibular disorders (TMD), sinusitis, neuralgias, salivary gland conditions, bone-related pathology, and oral mucosal diseases. The overlapping clinical features among these conditions make diagnosis particularly complex for general dentists and clinicians in primary care settings. Despite advances in diagnostic technology, the decision-making process in clinical practice often relies on a combination of subjective symptom assessment, physical examination, and basic diagnostic tools, many of which vary significantly in their diagnostic performance.1–4
The traditional approach to diagnosing oro-facial pain predominantly includes visual-tactile examination, pulp sensibility tests (e.g., thermal and electric), percussion tests, probing, and standard radiography. While these methods remain widely used, their diagnostic accuracy has not been clearly established across all etiologies. More advanced diagnostic aids, such as cone-beam computed tomography (CBCT), magnetic resonance imaging (MRI), salivary and serum biomarkers, and culture or histopathological examinations, are available but are not routinely employed due to accessibility, cost, or lack of clinical familiarity.5–8
Consequently, clinicians often face uncertainty in diagnosis of orofacial pain, which may lead to empirical treatments, misdiagnosis, unnecessary interventions, or delayed care. This uncertainty underscores the urgent need for a reliable evidence base on the diagnostic accuracy of various clinical signs, symptoms, and point-of-care (POC) tests, as they compare against advanced reference standards.1,3
The objective of this suite of nine systematic reviews is to evaluate the diagnostic performance of clinical symptoms, signs, clinical assessments, and POC tests done individually or in combination for various causes of oro-facial pain, using advanced diagnostic methods or consensus clinical criteria as reference standards. By synthesizing available evidence across diverse pain etiologies—including pulpal/periapical infections, periodontal disease, TMD, sinusitis, neural conditions, salivary gland disorders, bone pathologies, and mucosal conditions—this review series aims to, identify the most accurate and reliable diagnostic tools for each condition, and clarify the diagnostic pathway for clinicians working in general or primary care settings. Consequently, the goal is to equip dental practitioners with evidence-based guidance that enhances their ability to diagnose oro-facial pain accurately and efficiently. This will not only facilitate appropriate treatment planning but also reduce unnecessary interventions, improve patient outcomes, and optimize healthcare resources.
Objectives
This protocol was prepared in accordance with Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P).9 Reporting guidelines. The study objectives were designed using Patient, Index test, Reference test, Target condition (PIRT) guidelines.
The objective of the review is to undertake a series of reviews to establish the diagnostic accuracy of clinical signs, symptoms, and point-of-care (POC) tests for the detection and diagnosis of orofacial pain. We propose a new review for each identified origin of orofacial pain (eight reviews in total):
Review 1. Diagnosis of orofacial pain due to pulpitis and/or periapical pathology ( Table 1)
Table 1. Research Question 1.
What is the performance of symptoms, signs and Point of Care (POC) tests for the diagnosis of pulpitis and/or periapical pathology in patients reporting to a healthcare setting with the complain of oro-facial pain?
Review 2. Diagnosis of orofacial pain due to periodontitis and/or gingivitis ( Table 2)
Table 2. Research Question 2.
What is the performance of symptoms, signs, and POC tests for the diagnosis of periodontitis and/or gingivitis in patients reporting to a healthcare setting with the complain of oro-facial pain?
Review 3. Diagnosis of orofacial pain due to temporomandibular joint ( Table 3)
Table 3. Research Question 3.
What is the performance of symptoms, signs, clinical assessments and POC tests for the diagnosis of orofacial pain affecting the temporomandibular joint in patients reporting to a healthcare setting with the chief complain of oro-facial pain?
Review 4. Diagnosis of orofacial pain due to maxillary sinusitis ( Table 4)
Table 4. Research Question 4.
What is the performance of symptoms, signs, clinical assessments and POC tests for the diagnosis of maxillary sinusitis in patients reporting to a healthcare setting with orofacial pain?
Review 5. Diagnosis of orofacial pain of neural origin ( Table 5)
Table 5. Research question 5.
What is the performance of symptoms, signs, clinical assessments and POC for the diagnosis of neural pain in patients reporting to a healthcare setting with complaints of orofacial pain?
Review 6. Diagnosis of orofacial pain due to salivary gland conditions ( Table 6)
Table 6. Research Question 6.
What is the performance of symptoms, signs, clinical assessments and POC for the diagnosis of salivary gland conditions in patients presenting to a healthcare setting with complaints of orofacial pain?
Review 7. Diagnosis of orofacial pain originating from bone (maxilla or mandible) ( Table 7)
Table 7. Research Question 7.
What is the performance of symptoms, signs, clinical assessments and POC for diagnosing bone conditions in patients presenting with orofacial pain?
Review 8. Diagnosis of orofacial pain due to oral mucosal conditions ( Table 8)
Table 8. Research Question 8.
What is the performance of symptoms, signs, clinical assessments and POC for diagnosing oral mucosal conditions in patients presenting with orofacial pain?
Aligned to the objectives listed above, the specific research questions answered through the suite of systematic reviews are listed in Tables 1 through 8.
Methods
Eligibility criteria: We will include
• Retrospective/prospective cross sectional and cohort studies that evaluate the diagnostic accuracy of single index tests as well as studies that directly compare two or more index tests,
• Studies that evaluate test combinations alone or test combinations in comparison to a single test or other test combinations,
• Randomised controlled trials (RCTs) of the diagnostic test accuracy of one or more index tests in comparison to a refence test.
Information sources and search strategy
We will search PubMed, EMBASE, the Cochrane Library and SCOPUS for the eligible studies from inception to April 2025. The PubMed search strategy will be structured to ensure comprehensive retrieval of relevant studies related to the diagnostic performance of clinical assessments and Point of Care (POC) tests for the target conditions. The search will incorporate terms related to “diagnostic test accuracy,” “diagnostic accuracy,” “odds ratios,” “likelihood ratio,” “positive predictive value,” and “negative predictive value,” combined with specific conditions of interest. These conditions will include pulpitis, pulp exposure, pulp disease, periapical abscess, periapical pathology, gingivitis, periodontitis, temporomandibular infections, sinusitis, bacterial neuralgia, osteomyelitis of the jaw, and oral bacterial infections. Boolean operators (AND/OR) will be used to optimize search sensitivity and specificity. Filters such as “English language,” “human studies,” and the exclusion of systematic reviews, meta-analyses, and review articles will be applied to refine the results. Additional searches will be conducted in Cochrane, Embase and SCOPUS using similar terms, to ensure comprehensive coverage. The strategy will be iteratively refined to capture the most relevant literature while minimizing irrelevant results. The detailed search strategy can be accessed through the supplementary file.
Study selection
The search results will be uploaded on Covidence systematic review software for screening. The results of all searches will be screened and assessed independently by two review authors for inclusion. Any disagreements will be resolved through discussion and, if necessary, consultation with another clinical or methodological member of the author team. Studies will be excluded if the data are not presented in the format of a 2 x 2 contingency table or data regarding Diagnostic Accuracy Metrics is not reported. A PRISMA flowchart will be used to report the study selection process. Once agreement on inclusion is reached, the studies will be categorized according to their index test, dental disease and reference test.
Data extraction
Data will be extracted independently and in duplicate by two review authors using a piloted data extraction form based on the review inclusion criteria. Any disagreements will be resolved through discussion by the review team. Where data are reported for multiple index or refence tests, they will be extracted separately for each. Study authors will be contacted to obtain missing data or clarify characteristics not evident in the published paper.
The following data will be recorded for each study:
• Sample characteristics (age, gender, condition);
• Setting (country, disease prevalence, type of facility);
• Study information (design, reference standard, case definition, training and calibration of personnel);
• The type of index test(s) used (category, name, conditions, thresholds, if any);
• The type of refence test(s) used (category, name, conditions, thresholds, if any);
• Study results (true positive, true negative, false positive, false negative, any equivocal results, withdrawal).
Risk of bias (quality) assessment
We will use the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) to assess the risk of bias and applicability of the primary diagnostic studies across the four domains of participant selection, index test, reference standard, and flow and timing (Whiting 2011). A customized QUADAS tool will be prepared for the present systematic review. Quality assessment will be done independently by two review authors. Any disagreements will be resolved through discussion by the review team.
Strategy for data synthesis
The primary outcomes of interest will be true positive, true negative, false positive, false negative, sensitivity and specificity of the index tests. Secondary outcomes might include positive and negative likelihood ratios, diagnostic odds ratios (DORs), and the area under the summary receiver operating characteristic curve (AUC).
Meta-analysis
Where appropriate, and if enough comparable studies are identified, we will conduct a meta-analysis. A bivariate random-effects model may be used to jointly synthesize sensitivity and specificity estimates, accounting for within- and between-study variability and the potential correlation between the two measures. Summary point estimates will be presented with 95% confidence intervals. In cases where diagnostic thresholds vary substantially across studies, we will apply a hierarchical summary receiver operating characteristic (HSROC) model to explore threshold effects and to generate a summary ROC curve. This model will allow us to assess the influence of study-level covariates and estimate the area under the curve (AUC) as an overall measure of test performance.
Assessment of heterogeneity
We will assess heterogeneity visually through forest plots and SROC curves, and statistically by examining the variance of logit-transformed sensitivity and specificity estimates. Where substantial heterogeneity is suspected, we will explore potential sources using subgroup analysis or meta-regression, depending on the availability and quality of study-level data.
Subgroup and sensitivity analyses
Subgroup analyses may be conducted based on factors such as the type of diagnostic test (e.g., thermal, electric, percussion, or imaging), and the methodological quality of included studies as assessed by the QUADAS-2 tool. Sensitivity analyses might be performed to evaluate the robustness of the results by excluding studies at high risk of bias, small studies (e.g., fewer than 50 participants), or studies using unclear reference standards.
Assessment of reporting bias
If ten or more studies are included in each test comparison, we will assess potential reporting bias using Deeks’ funnel plot asymmetry test. A statistically significant non-zero slope might suggest the presence of publication bias.
Software
Statistical analyses will be performed using appropriate software. RevMan 5 may be used for basic forest plots and data management, while Stata18 (e.g., using the MIDAS or METANDI commands) will be employed for fitting bivariate and HSROC models.
GRADE assessment
We will use the GRADE approach adapted for diagnostic test accuracy studies to assess the certainty of the evidence for each diagnostic modality. Summary of Findings tables will be developed to present key results, incorporating evaluations of risk of bias, inconsistency, indirectness, imprecision, and publication bias.
Discussion
The complexity of diagnosing oro-facial pain lies in its multifactorial etiology and the substantial overlap in clinical presentations among various conditions. General practitioners and primary care dentists often rely on traditional diagnostic methods such as symptom assessment, visual-tactile examination, and basic radiography. However, the diagnostic accuracy of these tools varies widely, which can lead to misdiagnosis, unnecessary interventions, and delayed treatment.
This protocol addresses a critical gap in clinical practice by proposing a structured evaluation of the diagnostic performance of commonly used clinical signs, symptoms, and point-of-care tests across a wide spectrum of oro-facial pain conditions. By employing systematic review and meta-analytic methods, this suite of reviews aims to generate robust, evidence-based guidance that clinicians can apply in real-world settings.
Importantly, the protocol also highlights the growing availability of advanced diagnostic modalities such as cone-beam computed tomography, MRI, and biomarker-based testing. While these techniques show promise in improving diagnostic precision, their accessibility and cost may limit their routine use. By comparing these methods to traditional and POC tests, the review series may help define a more practical and cost-effective diagnostic workflow.
Overall, this work has the potential to enhance diagnostic confidence among clinicians, reduce the burden of diagnostic uncertainty, and ultimately improve outcomes for patients suffering from oro-facial pain.
Reporting guidelines
Figshare: PRISMA-P-checklist for manuscript titled DIAGNOSTIC TESTS FOR ORO-FACIAL PAIN: PROTOCOL FOR A SUITE OF SYSTEMATIC REVIEWS AND META-ANALYSES. DOI: https://doi.org/10.6084/m9.figshare.2883152610
Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).
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how to cite this article
Rai A, Mahuli SA, Mahuli AV et al. Diagnostic tests for oro-facial pain: protocol for a suite of systematic reviews and meta-analyses [version 1; peer review: awaiting peer review]. F1000Research 2025, 14:495 (https://doi.org/10.12688/f1000research.164451.1)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
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