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This paper is part of the Special Issue on Advancements in Dental Technology and Engineering: Innovations for Enhanced Patient Care 
Guest Editor: Dr. Giuseppe Minervini, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy. 

Received January 8, 2025, accepted May 5 2025, date of publication May 30 2025.

Review 

Newer Diagnostic Methods to Detect Oral Cancer and Their Ap-
plications in Prevention and Treatment Strategies: A Systematic 
Review
Sai Sree Kotari1, Bharath Kumar Konakanchi2, Supraja Salwaji3, Mohan Kumar Pasupuleti4,*, Prathyusha Kancherla5, Maria 
Maddalena Marrapodi6, Marco Cicciù7, and Giuseppe Minervini8,9

1 Biomedical and Health Informatics, University of North Carolina, Chapel Hill, North Carolina, United States. 
2 Health Informatics and Analytics, University of North Carolina, Charlotte, North Carolina, United States. 
3 Oral and Maxillofacial Pathology, Vishnu Dental College, Bhimavaram, Andhra Pradesh, India. 
4 Periodontics and Implantology, Vishnu Dental College, Bhimavaram, Andhra Pradesh, India. 
5 Private practitioner, Aswaraopeta, Telangana, India. 
6 Department of Woman, Child and General and Specialist Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy.
7 Department of Biomedical and Surgical and Biomedical Sciences, Catania University, 95123 Catania, Italy.
8 Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, 600077 Chennai, 
India.
9 Multidisciplinary Department of Medical-Surgical and Odontostomatological Specialties, University of Campania “Luigi Vanvitelli”, 80138 
Naples, Italy.

* Corresponding Author Email: mosups@gmail.com

ABSTRACT

Background: Oral cancer, which includes cancers of the lips, tongue, mouth, throat, and other oral tissues, is a serious health 
concern globally. It is one of the major causes of cancer-related mortality because of several factors, including the severity of 
certain oral malignancies and their late-stage detection. Objective: To comprehensively investigate recently developed technolo-
gies for detecting oral cancer and evaluate their accuracy, reliability, and potential application in both therapeutic and preventive 
contexts. Methods: A thorough literature search was performed using the PubMed, Scopus, and Web of Science databases, focus-
ing on works published between 2014 and 2024. This review evaluates various methods for diagnosing oral cancer, including 
advanced imaging techniques (MRI and CT scans), biomarker testing, molecular diagnostics, noninvasive salivary diagnostics, 
optical coherence tomography (OCT), and the application of artificial intelligence (AI) and machine learning (ML) to enhance 
diagnostic accuracy. Results: All relevant studies meeting the inclusion criteria were analyzed. Several important findings regard-
ing confocal laser scanning microscopy (CLSM) and OCT demonstrated high sensitivity and specificity in identifying oral cancer. 
This systematic review also highlights the promise of fluorescence spectroscopy, salivary biomarkers, genetic markers, and AI/
ML technologies in early disease detection and monitoring. Conclusion: New diagnostic procedures outperform traditional ones 
in accuracy and reliability in the detection of oral cancer. These innovations enable earlier diagnosis, facilitate targeted therapies, 
and support personalized treatment strategies. As preventive and monitoring strategies evolve, treatment efficacy improves, 
and patient trust and engagement increase, ultimately leading to better outcomes and enhanced quality of life for patients.

http://www.globalce.org
http://globalce.org
http://globalce.org
https://globalce.org/index.php/GlobalCE/DentalTechnology
mailto:mosups@gmail.com


Kotari, Konakanchi, Salwaji, Pasupuleti, Kancherla, Marrapodi, Cicciù, Minervini: Newer Diagnostic Methods to Detect Oral 
Cancer and Their Applications in Prevention and Treatment Strategies: A Systematic Review   

J Global Clinical Engineering Vol.7 Issue 2: 2025 38

Keywords—Clinical applications, Diagnostic methods, 
Early detection, Noninvasive techniques, Oral cancer, Sys-
tematic review.        

Copyright © 2025. This is an open-access article distributed under the terms 
of the Creative Commons Attribution License (CC BY): Creative Commons - At-
tribution 4.0 International - CC BY 4.0. The use, distribution or reproduction in 
other forums is permitted, provided the original author(s) and the copyright 
owner(s) are credited and that the original publication in this journal is 
cited, in accordance with accepted academic practice. No use, distribution or 
reproduction is permitted which does not comply with these terms.

BACKGROUND

Oral cancer accounts for approximately 3% of the total 
cases of cancer globally, establishing it as an important 
public health issue. This extensive range of cancers occurs 
in the epithelial lining of the oral cavity, encompassing the 
lips, tongue, floor of the mouth, buccal mucosa, and gums. 
Oral cancer is the most prevalent cancer in Indian men, 
exhibiting variation by region, with the highest incidence 
rates observed in South Asia.1–4

Early detection of oral cancer is crucial for improv-
ing treatment efficacy and survival rates. Conversely, 
oral cancer is often identified later in life, resulting in a 
grim prognosis and diminished quality of life. The early 
detection of oral cancer is hindered by the constraints of 
conventional diagnostic methods like visual examination, 
biopsy, and histological evaluation.5–9

 Recent technological advancements have led to the 
development of innovative diagnostic techniques that 
significantly enhance the early detection and monitoring 
of oral cancer. Notably, optical coherence tomography 
(OCT) provides high-resolution, real-time imaging of 
oral tissues, allowing clinicians to detect subtle epithelial 
changes indicative of malignancy.10–13 Fluorescence-based 
diagnostic instruments leverage the natural fluorescence 
properties of tissues to distinguish between healthy and 
abnormal areas, facilitating noninvasive, chairside screen-
ing. In addition, the analysis of salivary biomarkers such 
as DNA, RNA, proteins, and metabolites offers a promising, 
noninvasive approach for identifying molecular signatures 
associated with oral cancer, thus supporting both early 
diagnosis and disease progression monitoring.14–17

Early diagnosis of oral cancer can improve treatment 
outcomes and survival rates, and these new diagnostic 
tools show promise in this regard. The purpose of this 
systematic review is to establish the therapeutic value of 
novel diagnostic tools for oral cancer detection, as well as 
their diagnostic accuracy and application in oral cancer 
prevention and treatment strategies.18–21

This systematic review offers a thorough overview of 
the latest methods for detecting oral cancer, highlighting 
their clinical applications and diagnostic accuracy. The 
findings of the review are crucial for healthcare profes-
sionals, researchers, and policymakers in formulating 
effective approaches for the early detection and treatment 
of oral cancer.

METHODS

Study Design and Setting

During the months of October through December 
2024, this systematic review was conducted to examine 
and assess recently developed methods for diagnosing 
oral cancer, assessing their accuracy, reliability, and ap-
plications in preventative and therapeutic approaches at 
Vishnu Dental College in Bhimavaram, Andhra Pradesh. 

On October 19th, PROSPERO registered the current 
protocol with registration ID CRD42024598844. The 
systematic review was carried out in accordance with 
PRISMA (Preferred Reporting Items for Systematic Re-
search and Meta-Analysis) criteria. A strong agreement 
is suggested by a Kappa value of 0.75, which shows that 
the reviewers’ selection and extraction procedures were 
dependable and consistent. 

This study problem was structured using the PICO 
framework, which encompasses population, intervention, 
comparison, and outcome. The population consists of those 
who use tobacco products, drink alcohol, or have HPV 
infections, as well as those who are at risk of or have been 
diagnosed with oral cancer. Recent diagnostic technolo-
gies evaluated include liquid biopsy, fluorescence imaging, 
molecular diagnostics, and AI-based tools. Traditional 
diagnostic methods such as ocular inspection, histology, 
or conventional imaging methods were compared. Better 

https://creativecommons.org/licenses/by/4.0/
https://creativecommons.org/licenses/by/4.0/


39 J Global Clinical Engineering Vol.7 Issue 2 2025

Kotari, Konakanchi, Salwaji, Pasupuleti, Kancherla, Marrapodi, Cicciù, Minervini:  Newer Diagnostic Methods to Detect 
Oral Cancer and Their Applications in Prevention and Treatment Strategies: A Systematic Review   

early detection rates, better prevention and treatment 
planning techniques, and a decrease in the death and 
morbidity rates from oral cancer were the intended results. 

The systematic review’s goals were to compare the 
efficacy and uses of more recent diagnostic tools for the 
detection of oral cancer with more established methods, 
as well as to investigate how these approaches might be 
used to enhance patient outcomes through prevention and 
therapy. The study’s research question was, “What is the 
accuracy, early detection rate, and effect on prevention and 
treatment strategies of newer diagnostic methods for oral 
cancer compared to traditional diagnostic techniques?”

Study Eligibility Requirements

A variety of trial designs were included in the systematic 
review for a thorough evaluation of the more recent tech-
niques for diagnosing oral cancer. Randomized controlled 
trials (RCTs), prospective cohort studies, cross-sectional 
studies, retrospective studies, and comparative effective-
ness studies were all included in the study. These studies 
evaluated the safety and effectiveness of different treat-
ments in a controlled environment and provided strong 
evidence from 2013 to 2024. This systematic review did 
not consider the following study categories: brief com-
munications, editorial letters, mini-reviews, studies that 
did not follow the objectives of the review, and papers 
written in languages other than English.

We developed a list of terms to look for in the databases 
based on our knowledge of the subject and previous re-
search. Oral cancer, oral squamous cell carcinoma (OSCC), 
novel diagnostic techniques, molecular diagnostics, and 
biomarkers in oral cancer were the search phrases used 
to search the PubMed databases. Boolean operators were 
used to combine these keywords, yielding thorough and 
pertinent results.

(“oral cancer” OR “mouth cancer” OR “oral squamous cell 
carcinoma”) AND (“new diagnostic methods” OR “emerging 
techniques” OR “molecular diagnostics” OR “liquid biopsy” 
OR “fluorescence imaging” OR “artificial intelligence”) AND 
(“prevention” OR “treatment strategies” OR “early detec-
tion” OR “risk stratification”).

(Newer[All Fields] AND (“diagnosis”[MeSH Terms] OR 
“diagnosis”[All Fields] OR “diagnostic”[All Fields]) AND 

(“methods”[Subheading] OR “methods”[All Fields] OR 
“methods”[MeSH Terms]) AND Detect[All Fields] AND 
(“mouth neoplasms”[MeSH Terms] OR (“mouth”[All Fields] 
AND “neoplasms”[All Fields]) OR “mouth neoplasms”[All 
Fields] OR (“oral”[All Fields] AND “cancer”[All Fields]) OR 
“oral cancer”[All Fields]) AND Applications[All Fields] AND 
(“prevention and control”[Subheading] OR (“prevention”[All 
Fields] AND “control”[All Fields]) OR “prevention and 
control”[All Fields] OR “prevention”[All Fields]) AND 
((“treatment”[All Fields] AND “strategies”[All Fields]) 
OR “treatment strategies”[All Fields])) AND (“systematic 
review”[All Fields] OR “systematic reviews as topic”[MeSH 
Terms] OR “systematic review”[All Fields])

Literature Search Protocol

Two reviewers independently searched for the publications. 
To conduct a focused, systematic review, we looked 
through relevant papers that were available in electronic 
databases, including PubMed, Web of Science, and Scopus. 

Rayyan was used during the study selection process 
to reject unsuitable abstracts and nominations and to 
eliminate duplicate search results from multiple databases. 
The collected data were closely examined to ensure 
that they met the established inclusion and exclusion 
criteria. When the data from the included studies were 
too inconsistent or varied to be quantitatively merged, a 
systematic review was conducted instead of a meta-analysis.

Selection of Included Research Articles

For more knowledge of the state of research on this 
subject, the discovered papers were filtered to include clinical 
studies and RCTs. Their study goals and importance were 
then added to this review. A thorough synopsis of these 
research publications is provided in the table, emphasizing 
their salient features, approaches, and conclusions. 

Quality Assessment of Studies

 AMSTAR 2 (A MeaSurement Tool to Assess systematic 
Reviews) is a previously published and validated tool 
for assessing the methodological quality of systematic 
reviews (with and without meta-analyses). Where AMSTAR 
only considered RCTs, AMSTAR 2 considers both RCTs 
and nonrandomized studies, therefore diversifying the 
studies that could be reviewed. The tool comprises 16 



Kotari, Konakanchi, Salwaji, Pasupuleti, Kancherla, Marrapodi, Cicciù, Minervini: Newer Diagnostic Methods to Detect Oral 
Cancer and Their Applications in Prevention and Treatment Strategies: A Systematic Review   

J Global Clinical Engineering Vol.7 Issue 2: 2025 40

items, with each item touching upon important aspects 
of review methodology. The quality of all included 
systematic reviews was assessed in this study, using 
appropriate rating tools. AMSTAR 2 provides valuable 
criteria in umbrella reviews to critically appraise the 
included reviews by evaluating items for the risk of bias 
(RoB), search strategy, and rationale for excluding studies.

RESULTS

Data Extraction and Synthesis Process

On October 19th, 2024, a preliminary keyword search 
was conducted in numerous electronic databases, including 
PubMed, Web of Science, and Scopus, yielding 729 results. 
After applying preliminary relevance filters, 59 articles 
were retained for further evaluation. Of these, 17 articles 
met the intended inclusion criteria and were considered 
relevant. A final set of seven systematic reviews met the 
inclusion criteria and were included in this umbrella review, 
with a special focus on the use of more modern diagnostic 
tools for the detection of oral cancer and its impact on 
prevention and treatment approaches (Figure 1).5,7,9,10,12,13,22

FIGURE 1. PRISMA 2020 flow diagram for new systematic re-
views, which included searches of databases and registers only.

Newer Diagnostic Methods to Detect Oral Cancer

Enhanced tools for diagnosing oral cancer now include 
narrow band imaging (NBI), confocal laser scanning 
microscopy (CLSM), saliva-based biomarkers, fluorescence 
diagnostic techniques, and OCT. These advanced technologies 
provide earlier detection, improve treatment outcomes, 
and enhance the sensitivity and accuracy of oral cancer 
screening. For example, fluorescence-based diagnostic tools 
can detect abnormal changes in cells, and OCT provides 
high-resolution images of the oral mucosa (Table 1).

To improve the results of treatment and reduce the 
affection rate and mortality ratio related to oral cancer, the 
current approach to prevention and treatment includes 
individualized medicine, immunotherapy, target therapy, 
and lighting therapy (PDT). Robot surgery is included. For 
instance, immunotherapy employs the body’s immune 
system to fight oral cancer, while personalized medicine 
involves customizing treatment plans for each patient 
based on their genetic profiles (Table 1).

The use of artificial intelligence (AI) and machine learning 
(ML) algorithms to study large datasets and identify trends 
is a significant improvement in the detection and treatment 
of oral cancer. Another potential area of research is liquid 
biopsies, which identify biomarkers in physiological fluids 
like saliva. Scientists are also researching novel medicines 
and developing personalized oral cancer tumor models 
using 3D printing and bioprinting technology (Table 1).

Salivary biomarkers, fluorescence-based devices, and 
optical OCT are cutting-edge diagnostic techniques that 
have dramatically increased the sensitivity and precision 
of oral cancer diagnosis, allowing for earlier and more 
accurate therapy. At the same time, advanced preventive 
and therapeutic approaches, including immunotherapy, 
targeted therapies, and personalized medicine, are 
transforming patient care, improving outcomes, and 
reducing the impact of the disease. Recent results, such 
as liquid biopsy, 3D biological suppression, and diagnostic 
diagnosis controlled by AI, indicate the possibility of 
improving oral cancer detection and treatment (Table 1).



41 J Global Clinical Engineering Vol.7 Issue 2 2025

Kotari, Konakanchi, Salwaji, Pasupuleti, Kancherla, Marrapodi, Cicciù, Minervini:  Newer Diagnostic Methods to Detect 
Oral Cancer and Their Applications in Prevention and Treatment Strategies: A Systematic Review   

TABLE 1. The qualitative characteristics and conclusive statements of the newer diagnostic methods to detect oral cancer.

Author, Year,
& Reference 

No.

Aim of 
Study Search Strategy

No. of 
Studies 

Included

Screening 
Method Used

Outcome 
Measures Summary

Brocklehurst, 
et al.5

To evaluate how 
well the existing 

screening 
techniques 

reduce the death 
rate from oral 

cancer.

Cochrane Central 
Register of Controlled 

Trials
MEDLINE via OVID
EMBASE via OVID

CANCERLIT via 
PubMed

1

Visual 
examination, 

toluidine blue, 
fluorescence 
imaging, or 

brush biopsy.

Individuals 
diagnosed with 

stage III or worse 
oral cancer.

Survival rates 
across the 

population.

In high-risk 
individuals, there 
is evidence that a 

visual examination 
as part of a 
population-

based screening 
program lowers 
the death rate 

from oral cancer.

Jerjes, et al. 
20247

To evaluate 
optical coherence 

tomography’s 
(OCT) diagnostic 

precision in 
identifying oral 
malignancies.

PubMed, Embase, 
Scopus, Google Scholar, 

Cochrane Central 
Register, and Web of 

Science

9
 OCT

Artificial 
intelligence (AI)

Diagnostic 
outcomes, such 

as sensitivity and 
specificity.

OCT has very high 
sensitivity and 

specificity, making 
it a promising 

new diagnostic 
technique for oral 

cancer.

Bastías, et al. 
20249

To conduct a 
scoping review 

of salivary 
molecules 
examined 

as potential 
indicators for oral 

squamous cell 
cancer (OSCC) 

diagnosis.

EBSCO, PubMed 
(MEDLINE), Scopus, 
and Web of Science

62 studies 
were 

included. 
100 

molecules 
were 

assessed. 

TNF-α, IL-1β, 
IL-6, IL-8, LDH, 
MMP-9, TNF-α, 
IL-1β, IL-6 IL-

8, LDH, and 
MMP-9 are the 

most promising 
salivary 

biomarkers 
for cancer 
detection.

Ability for 
detecting 

OSCC and oral 
potentially 
malignant 
disorders 
(OPMDs), 

OSCC outcome 
prediction, and 
the prediction 

of the malignant 
transformation of 

OPMDs.

It may be possible 
to use salivary 
biomarkers to 

help detect, 
manage, and 
forecast the 
malignant 

transformation 
and spread of 

OSCC and OPMDs.



Kotari, Konakanchi, Salwaji, Pasupuleti, Kancherla, Marrapodi, Cicciù, Minervini: Newer Diagnostic Methods to Detect Oral 
Cancer and Their Applications in Prevention and Treatment Strategies: A Systematic Review   

J Global Clinical Engineering Vol.7 Issue 2: 2025 42

Author, Year,
& Reference No.

Aim of 
Study Search Strategy No. of Screening Method 

Used Outcome Measures Summary

Kim, et al.10

To examine the 
effectiveness of OCT 
in identifying malignant 
lesions in the mouth.

PubMed,
Cochrane Central Register 

of Controlled Trials
Embase, 

Web of Science Scopus, 
Google Scholar.

12 OCT

The diagnostic odds 
ratio (DOR), along 
with summary 
receiver operating 
characteristic curve 
(SROC), area under 
SROC, sensitivity, 
specificity, and negative 
predictive values, 
were the outcomes.

OCT can help in 
the diagnosis and 
monitoring of oral cancer 
and oral precancerous 
lesions because it is 
noninvasive, produces 
quick results without 
exposing users to 
radiation, and is quick.

González-Moles, 
et al. 202212

To find evidence gaps 
and suggest future 
research directions that 
ought to be pursued and 
formulate improvement 

plans.

MEDLINE
Embase,

Cochrane Central Register 
of Controlled Trials

DARE

12 Light-based detection 
or oral spectroscopy.

New cases per year, 
deaths annually, and 

mortality rate.

Patients, healthcare 
professionals, and 
health services are all 
involved in the many 
factors that contribute 
to the delay in the 
diagnosis of oral cancer.

Li, et al. 202413

To assess the differences 
in accuracy between 
the various imaging 
techniques used in these 
diagnostic procedures.

Embase, Web of Science, 
PubMed, and Scopus. 17 AI

Overall diagnostic 
odds ratio (DOR), 
sensitivity, specificity, 
negative predictive 
values, and summary 
receiver operating 
characteristic (SROC) 

curves.

With billions of phone 
users worldwide, AI-
based identification 
employing clinical 
photography has a 
high DOR and is readily 

available now.

Almangush, et 
al.22

To provide a 
summary of the data 
currently available on 
immunohistochemistry 
prognostic biomarkers 
for oral tongue squamous 
cell carcinoma (OTSCC). 

Scopus, Ovid Medline, 
Web of Science, and 

Cochrane Library.
11

Immunohistochemical 
p r o g n o s t i c 

biomarkers.

Identifying informative 
prognostic biomarkers 
for oral tongue 
squamous cell 

carcinoma.

Many biomarkers have 
been proposed as helpful 
predictors of OTSCC; 
however, the overall 
quality of the original 
research reporting 
and methodology is 
inadequate, making 
it impossible to draw 
trustworthy conclusions.



43 J Global Clinical Engineering Vol.7 Issue 2 2025

Kotari, Konakanchi, Salwaji, Pasupuleti, Kancherla, Marrapodi, Cicciù, Minervini:  Newer Diagnostic Methods to Detect 
Oral Cancer and Their Applications in Prevention and Treatment Strategies: A Systematic Review   

 Quality Assessment Results

The AMSTAR 2 assessment of seven systematic reviews 
found that, while all reviews included well-defined PICO 
components, performed study selection and data extraction 
in duplicate, and reported potential conflicts of interest, they 
were overall rated as “critically low” because of several key 
methodological flaws. A major issue in all reviews was a 
lack of disclosure about the funding sources for the included 
studies, which raised questions about potential bias(Table 2).

Furthermore, most evaluations did not achieve this 
transparency criterion, with only a few providing a thorough 
list or explanation for rejected studies. Protocol pre-
specification and deviations were not adequately reported 
by Bastías, et al.,9 González-Moles, et al.,12 and Almangush,22 
further weakening their credibility. Although most reviews 
used appropriate techniques for RoB assessment, Bastías 
et al.,9 did not perform this adequately, and González-
Moles et al.,12 provided partial information (Table 2).

Furthermore, the reliability of the results has been 
compromised by the fact that only a few evaluations 
have adequately addressed publication bias. Although 
these evaluations have potential in certain areas, their 
overall reliability and credibility are compromised by 
fundamental methodological flaws.

Despite meeting important quality standards (e.g., 
PICO, duplicate data extraction, and conflict of interest 
declarations), major issues such as insufficient risk of 
bias (RoB) assessment, opaque exclusion criteria, and 
nondisclosure of funding sources compromise the overall 
credibility of reviews. This emphasizes how future 
systematic reviews must follow stricter guidelines in 
order to increase their caliber and dependability.

DISCUSSION

This systematic review sought to provide an overview 
of more modern techniques for diagnosing oral cancer, as 
well as their use in preventative and treatment approaches. 
The study highlights the promise of newer diagnostic 
approaches, such as salivary biomarkers, fluorescence-
based diagnostic tools, and OCT, in detecting oral cancer 
early on.

This review examined several diagnostic options, and 
OCT and biomarker-based diagnostics are perhaps most 
encouraging in the area of early detection of oral cancers. 
OCT uses noninvasive, real-time imaging for cross-sectional 
views of oral tissues with near-microscopic resolution. 
Changes at the tissue level can be detected foundationally 
before clinically visible signs. Moreover, the tissue depth 
imaging supplies added security in differentiating normal, 
dysplastic, and malignant tissues, which improves our 
diagnostic abilities, and responses are moved toward 
a fraction of earlier intervention in terms of treatment.

Similarly, salivary and molecular biomarkers are also 
a noninvasive means to detect cancer-related changes 
occurring at the molecular level. Salivary biomarkers such 
as proteins, DNA mutations, RNA transcripts, etc., can 
determine early-stage malignancies and may be applied as 
monitoring tools to help surveil disease and or against the 
recurrence of disease. These two technologies are a great 
stride forward in noninvasive diagnostics and hold serious 
promise as a clinically active emerging technology in dentistry.

Newer Diagnostic Tools

According to the review’s conclusions, modern diagnostic 
tools are more sensitive and specific than traditional 
methods. According to Global Burden of Disease Cancer 
Collaboration (2019),1 OCT offers a 92% sensitivity and 
85% specificity for detecting oral cancer. Likewise, Bray 
F et al. (2018) demonstrated that a fluorescence-based 
diagnostic approach can identify oral cancer with a 
sensitivity of 95% and a specificity of 90%.2

New Prevention and Treatment Strategies

Innovative techniques to prevent and cure oral cancer 
are also being investigated.3 Likewise, Petersen in 2018 
found that merging visual examination with fluorescence-
based diagnostic methods can aid in the early detection 
of oral cancer.3

The most recent diagnostic techniques for identifying 
oral cancer are assessed in these systematic reviews, 
which also investigate their potential uses in therapy and 
prevention.11–13 The research focuses on cutting-edge 
diagnostic methods that have the potential to improve 
early detection and clinical outcomes, such as liquid 



Kotari, Konakanchi, Salwaji, Pasupuleti, Kancherla, Marrapodi, Cicciù, Minervini: Newer Diagnostic Methods to Detect Oral 
Cancer and Their Applications in Prevention and Treatment Strategies: A Systematic Review   

J Global Clinical Engineering Vol.7 Issue 2: 2025 44

TABLE 2. AMSTER 2 Checklist.

Sl. 
No AMSTER 2 Checklist Brocklehurst, 

et al.5
Jerjes, 
et al.7

Kim, et 
al.10

Bastías, 
et al.9

González-
Moles, et 

al.12

Li, et 
al.13

Almangush, 
et al.22 

(2017)

1. Did the research questions and inclusion criteria for the 
review include the components of PICO? Yes Yes Yes Yes Yes Yes Yes

2.

Did the review report contain an explicit statement that the 
review methods were established prior to the review and 
did the report justify any significant deviations from the 

protocol?

Yes Yes Yes No No Yes No

3. Did the review authors explain their selection of the study 
designs for inclusion in the review? Yes Yes Yes Yes Yes Yes Yes

4. Did the review authors use a comprehensive literature search strategy? Yes Yes Yes Yes Yes Yes Yes

5. Did the review authors perform study selection in duplicate? Yes Yes Yes Yes Yes Yes Yes

6. Did the review authors perform data extraction in duplicate? Yes Yes Yes Yes Yes Yes Yes

7.
Did the review authors provide a list of excluded studies and justify 

the exclusions?
Partial Partial Partial No No No No

8.
 Did the review authors describe the included studies in adequate 

detail?
Yes Yes Yes YES Partial Yes Yes

9.
Did the review authors use a satisfactory technique for assessing 
the risk of bias (RoB) in individual studies that were included in 

the review?
Yes Yes Yes NO Partial Yes Partial

10.
Did the review authors report on the funding sources for the studies 

included in the review?
No No No No No No No

11.
If meta-analysis was performed, did the review authors use appropriate 

methods for the statistical combination of results?
N/A N/A Yes No N/A Yes Yes

12.
If meta-analysis was performed, did the review authors assess the 
potential impact of RoB in individual studies on the results of the 

meta-analysis or other evidence synthesis?
N/A N/A Yes N/A N/A Yes Partial

13.
Did the review authors account for RoB in individual studies when 

interpreting/discussing the results of the review?
Yes Yes Yes No Yes Yes Yes

14.
Did the review authors provide a satisfactory explanation for, and 
discussion of, any heterogeneity observed in the results of the review?

Yes Yes Yes Yes Yes Yes Yes

15.
If they performed quantitative synthesis, did the review authors carry 
out an adequate investigation of publication bias (small study bias) 

and discuss its likely impact on the results of the review?
N/A N/A Yes Yes No No No

16.
Did the review authors report any potential sources of conflict of 
interest, including any funding they received for conducting the review

Yes Yes Yes Yes Yes Yes Yes

Review Quality
Critically 

low
Critically 

low
Critically 

low
Critically 

low
Critically 

low
Critically 

low
Critically 

low



45 J Global Clinical Engineering Vol.7 Issue 2 2025

Kotari, Konakanchi, Salwaji, Pasupuleti, Kancherla, Marrapodi, Cicciù, Minervini:  Newer Diagnostic Methods to Detect 
Oral Cancer and Their Applications in Prevention and Treatment Strategies: A Systematic Review   

biopsy, optical imaging, molecular biomarkers, and AI-
based diagnostic tools.14–17

By identifying specific tumor markers, these cutting-
edge diagnostic approaches can guide individualized 
treatment strategies and significantly improve screening 
programs, particularly in high-risk populations. Nonetheless, 
obstacles still need to be addressed, such as consistency, 
cost, and availability.18–21

Comparison with Existing Literature

Brocklehurst, et al.5 conducted a systematic review to 
assess the effectiveness of current screening methods in 
decreasing oral cancer mortality. The findings of the study 
stated that a visual examination as part of a population-
based screening program reduces the mortality rate of 
oral cancer in high-risk individuals. In addition, there is a 
stage shift and improvement in survival rates across the 
population as a whole.

Jerjes, et al.7 conducted a systematic review to assess the 
diagnostic accuracy of OCT in the detection of oral cancers 
and to investigate the feasibility of combining OCT with AI 
and other imaging modalities to improve clinical outcomes 
and diagnostic accuracy in oral healthcare. The results of 
the study stated that OCT could play a very prominent 
role as a new diagnostic tool for oral cancer, with very 
high sensitivity and specificity. Future research pointed 
toward integrating OCT with other imaging methods and 
AI systems in providing better accuracy of diagnoses and 
more clinical usability.

Bastias, et al.9 conducted a systematic assessment of 
salivary molecules as possible markers for identifying oral 
squamous cell carcinoma. The research found that TNF-α, 
IL-1β, IL-6, IL-8, LDH, and MMP-9 were the most frequently 
utilized biomarkers for diagnosing oral squamous cell 
carcinoma. The findings of this systematic review align 
with the present review.

Kim, et al.10 performed a comprehensive assessment 
of oral lesions by utilizing coherent optical coherence 
tomography (OCT), and the findings were contrasted with 
organizational data. According to the study’s findings, 
OCT can help with the diagnosis and monitoring of oral 

cancer and oral precancerous lesions, is noninvasive, and 
yields quick results without exposing patients to radiation.

González-Moles, et al.12 aimed to better understand and 
explore the reasons underlying this fact, as well as identify 
evidence gaps and create improvement methods. Results 
stated that improving this critical component, which has 
remarkable consequences for prognosis, is a significant 
problem with little chance of being resolved very soon, 
according to this scoping assessment of systematic studies 
on the present level of knowledge addressing delayed 
diagnosis in oral cancer. 

Li, et al.13 carried out a study to consider the use of 
artificial intelligence (AI) algorithms in detecting oral 
potentially malignant disorders (OPMD) and oral cancers, 
and to evaluate differences in accuracy across the various 
imaging modalities used in this diagnosis. AI detection in 
this regard using clinical photography has a high DOR, and 
is now widely available to the billions of phone subscribers 
around the world.

In order to compile the available data on immunohisto-
chemistry prognostic biomarkers for oral tongue squamous 
cell carcinoma (OTSCC), Almangush, et al.22 carried out 
a comprehensive review. Many biomarkers have been 
proposed as helpful predictors of OTSCC; however, the 
overall quality of reporting and methodology of the 
original research is inadequate, making it impossible to 
draw trustworthy conclusions.22

In conclusion, despite substantial progress in diagnostic 
techniques for oral cancer, additional investigation and 
standardization of these methods are necessary to enhance 
the therapeutic benefits in early detection, prevention, 
and tailored treatment plans.23–25

Limitations

There are a few limitations to this review. First and 
foremost, the review only included English language 
articles, which would have excluded relevant studies 
produced in other languages. Second, only studies utilizing 
more contemporary diagnostic tools were included in 
the review, which may have excluded relevant studies 
employing more traditional diagnostic methods.



Kotari, Konakanchi, Salwaji, Pasupuleti, Kancherla, Marrapodi, Cicciù, Minervini: Newer Diagnostic Methods to Detect Oral 
Cancer and Their Applications in Prevention and Treatment Strategies: A Systematic Review   

J Global Clinical Engineering Vol.7 Issue 2: 2025 46

Clinical Implications

The findings of the review have major clinical implications. 
Above all, enhanced early detection of oral cancer can 
result in timely intervention and treatment, thanks to 
sophisticated diagnostic technology. Improved diagnostic 
procedures can also help to reduce the morbidity and 
mortality of oral cancer.26

Future Perspectives

Future research should primarily focus on developing 
and validating more advanced diagnostic equipment for 
the detection of oral cancer. It should also investigate the 
clinical utility and cost-effectiveness of newer diagnostic 
tools for detecting oral cancer.27,28

CONCLUSION

Finally, this systematic review emphasizes the importance 
of improved diagnostic technologies in detecting oral 
cancer at an early stage. The paper also discusses novel 
ways for preventing and treating oral cancer. The findings 
of this analysis have important clinical consequences, 
highlighting the need for additional research in this field.

SUPPLEMENTARY MATERIALS

Not applicable.

AUTHOR CONTRIBUTIONS

 Conceptualization, S.S.K and B.K.K; Methodology, 
S.S.; Software, S.S.; Hardware, M.K.P., Validation, M.M.M., 
M.C., and M.K.P.; Formal Analysis, P.K.; Investigation, 
G.M.; Resources, S.S.K.; Data Curation, B.K.K.; Writing–
Original Draft Preparation, S.S.; Writing–Review & Editing, 
M.K.P; Visualization, M.M.M; Supervision, G.M.; Project 
Administration, M.C.; Funding Acquisition, G.M.

ACKNOWLEDGMENTS

We are thankful to Vishnu Dental College, Bhimavaram, 
Andhra Pradesh, India; the University of North Carolina 

Chapel hill; and the University of North Carolina, Charlotte 
for facilitating this research work.

FUNDING

This research received no external funding.

DATA AVAILABILITY STATEMENT

 Not applicable.

CONFLICTS OF INTEREST

The authors declare they have no competing interests.

ETHICS APPROVAL AND CONSENT TO PARTICIPATE 

Not applicable.

CONSENT FOR PUBLICATION

Not applicable.

FURTHER DISCLOSURE

Not applicable.
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