Diagnostic efficacy of computed tomography and magnetic resonance imaging in detection of cervical lymph node metastasis among patients with oral cancer in India – Systematic review and meta-analysis

Saraswathi K Gopal; S Priyadharshini; V Poongodi; BG Harsha Vardhan

doi:10.4103/jhnps.jhnps_66_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 10 | Issue : 2 | Page : 132-141

Diagnostic efficacy of computed tomography and magnetic resonance imaging in detection of cervical lymph node metastasis among patients with oral cancer in India – Systematic review and meta-analysis

Saraswathi K Gopal, S Priyadharshini, V Poongodi, BG Harsha Vardhan
Department of Oral Medicine and Radiology, Faculty of Dentistry, Meenakshi Ammal Dental College and Hospital, MAHER University, Chennai, Tamil Nadu, India

Date of Submission	22-Sep-2022
Date of Decision	14-Nov-2022
Date of Acceptance	15-Nov-2022
Date of Web Publication	15-Dec-2022

Correspondence Address:
S Priyadharshini
Postgraduate, Department of Oral Medicine and Radiology, Faculty of Dentistry, Meenakshi Ammal Dental College and Hospital, MAHER University, Chennai.95, Tamil Nadu
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jhnps.jhnps_66_22

Abstract

Background: Oral cancer in India accounts for two-third of global incidence. Ninety percent are squamous cell type that are prone to neck lymph node metastasis. Computed tomography (CT) and magnetic resonance imaging (MRI) are common imaging methods used in our clinical practice for treatment planning, determine the prognosis and after treatment follow-up. Aim: The aim of this study was to assess the diagnostic efficacy of CT and MRI in detecting cervical lymph node metastasis among oral cancer patients in India using systematic review and meta-analysis. Methods: Literature search was conducted by manual search as well as in academic databases such as Scopus, PubMed, Medline, ScienceDirect, and Google Scholar from 2000 to 2021. Based on inclusion and exclusion criteria's, studies were analysed and tabulated. Qualitative assessment of included studies was done with QUADAS-2 which assessed the risk of bias. Further meta-analysis was done to know the efficacy of CT and MRI in identifying lymph node metastases. Results: A total of 14 studies including 516 participants were involved. With overall pooled sensitivity and specificity in the meta-analysis, CT showed a sensitivity of 92% and specificity of 70% and MRI had a sensitivity of 75% and specificity of 91%, which was identified in ROC curve in detecting the cervical lymph node metastasis. The diagnostic criteria for MRI and CT in identifying cervical lymph node metastasis includes key features like increases in size, round shape, structural changes, and extra nodal extension. Conclusion: CT has a good sensitivity and MRI has a good specificity, which are essential for selective neck dissection.

Keywords: Cervical lymph node, computed tomography, diagnostic efficacy, lymph node metastasis, magnetic resonance imaging, oral carcinoma

How to cite this article:
Gopal SK, Priyadharshini S, Poongodi V, Harsha Vardhan B G. Diagnostic efficacy of computed tomography and magnetic resonance imaging in detection of cervical lymph node metastasis among patients with oral cancer in India – Systematic review and meta-analysis. J Head Neck Physicians Surg 2022;10:132-41

How to cite this URL:
Gopal SK, Priyadharshini S, Poongodi V, Harsha Vardhan B G. Diagnostic efficacy of computed tomography and magnetic resonance imaging in detection of cervical lymph node metastasis among patients with oral cancer in India – Systematic review and meta-analysis. J Head Neck Physicians Surg [serial online] 2022 [cited 2023 Jun 4];10:132-41. Available from: https://www.jhnps.org/text.asp?2022/10/2/132/363931

Introduction

Oral carcinomas are the 11^th most common cancer in Asia, with 66% of global incidence and mortality rate of 74% according to the Global Observatory of Cancer 2020.^[1] Significant incidence is seen around the world due to environmental changes, lifestyle as well as habit of using smoke and smokeless tobacco, reverse smoking, or betel quid chewing. Ninety percent of oral cancers are squamous cell type which disseminate via regional lymphatics to cervical lymph node. : Metastasis of the node reduces the survival rate of the patient by 50% and when it involves contralateral side node it further reduces the survival by 25%.^[2] Hence, identification of lymph node metastasis and staging of oral carcinomas are critical for appropriate management like selective or radical neck dissection, followed by radiotherapy and/or chemotherapy depending on the pathological findings of the nodes. Computed tomography (CT) and magnetic resonance imaging (MRI) are common imaging methods used in our clinical practice for treatment planning, determine the prognosis and after treatment follow-up. Imaging science has improved accuracy compared to clinical palpation and plays an important role in identifying occult metastasis.^[3] However, to determine which one of these two techniques (MRI/CT) is better than the other is critical for providing guidance in clinical practice. Meanwhile, relevant studies utilized different diagnostic criteria in identifying these metastatic lymph nodes, hence a comprehensive criterion that is most appropriate for identification has to be determined. India accounts for one-third of global cancer incidence according to the WHO 2018. About 70% of the cases are reported in the advanced stages (American Joint Committee on Cancer, Stage III-IV). Detection in the late stage leads to very low chances of cure or almost negative and around 5-years survival rate seen in 20% of cases.^[4] Hence, the incidence of these cases drawn interest for comprehensive evaluation in Indian population.

The aim of this study was to assess the diagnostic efficacy of CT and MRI for detecting cervical lymph node metastasis among oral cancer patients in India and to establish the unified diagnostic imaging criteria from these studies in identifying cervical lymph node metastasis using systematic review and meta-analysis.

Materials and Methods

Inclusion criteria

The inclusion criteria were as follows: (1) types of study: diagnostic accuracy test studies designed as cohort studies in humans; (2) participants: Indian patients with biopsy-proven oral cancer as primary site; (3) index tests: CT and/or MRI; (4) target condition: cervical lymph node metastasis; (5) reference standard: histopathology examination; (6) outcome: rates of sensitivity, specificity, and diagnostic accuracy or true positive (TP), false positive (FP), false negative (FN), and true negative (TN) that could be used to calculate them; and (7) full article available

Exclusion criteria

Exclusion criteria were (1) animal studies; (2) diagnostic accuracy of other imaging modalities other than CT or MRI, (3) studies not done in Indian population; (4) evaluation of conditions other than cervical lymph node metastasis; (5) cancers other than oral cancer or secondaries in oral cavity; (6) lack of confirmed evidence by pathological examination; (7) studies where the data such as sensitivity, specificity, accuracy or TP, FP, FN, and TN are not available; and (8) review or meta-analysis or short communication, abstract.

Literature search

Manual search as well as academic databases search in Scopus, PubMed, Medline, ScienceDirect, and Google Scholar for studies published within the last 21 years (2000 to 2021) was carried out. Both Medical Subject Headings and free text words were used in the search strategy with the following terms: oral cancer, oral neoplasm, oral squamous cell carcinoma, cervical lymph node, metastasis, Computed Tomography, Magnetic Resonance Imaging, diagnostic accuracy, sensitivity, specificity, and India. Once relevant articles were identified, their reference lists were searched for additional articles.

Study selection

All the articles were independently examined for the titles and abstracts of each search record to remove obviously irrelevant ones, not statistically analyzed. Later, full-text articles of potentially eligible ones were retrieved and further examined according to the inclusion criteria.

Data extraction

All the articles were independently reviewed and extracted the key information of each eligible paper, such as first author name, year, study design, oral cancer site, diagnostic criteria, imaging modality used, rates of sensitivity, specificity, accuracy, positive predictive value and negative predictive value, TP, TN, FN, and FP based on “inclusion and exclusion criteria” mentioned above.

Types of bias in diagnostic accuracy test studies

The quality of diagnostic accuracy studies assessment is determined by their design, sampling methods, testing involved, blinding in the process of interpreting tests, and integrity of study report. Bias in diagnostic accuracy studies are selection bias and spectrum bias in patient selection; information bias in index test; misclassification bias, partial verification bias in reference test; and disease/condition progression bias, differential verification bias, information bias, incorporation bias in flow and timing; these can be assessed using the Quality Assessment of Diagnostic Accuracy Studies statement-2 (QUADAS-2).^[5]

Quality assessment

The methodological quality of included studies was assessed by QUADAS-2, which included four domains: patient selection, index test, reference standard, and flow and timing. Each domain was assessed in terms of risk of bias and the first three headings were assessed in terms of concerns regarding applicability. Signaling questions were included to assist judgments on risk of bias [Table 1].

Table 1: Quality Assessment of Diagnostic Accuracy Studies statement.2 analysis with signaling questions for assessment of risk of bias

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Results

Selection of literature

Two hundred and forty-one articles were identified in data base and manual search. Among them, after removing the studies that did not determine diagnostic accuracy, which were statistically irrelevant, involving imaging modalities other than CT or MRI and review articles, we identified 67 studies. On further analysis we excluded studies done outside India, and complete reading of remaining articles was carried out. Based on our inclusion criteria we finally got 14 full text articles for our systematic review. [Figure 1] shows the PRISMA guidelines followed in our systematic review and meta-analysis.

Figure 1: PRISMA flowchart

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Study characteristics

Of these 14 studies^{[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19]} included [Figure 2], 1 study included both MRI and CT, 2 studies were only MRI, and 11 studies were only CT. Total participants in these studies is 516 among them 20 underwent both MRI and CT, 85 underwent only MRI and 411 underwent only CT. The sites of oral cancer involved in these studies include buccal mucosa, lip, tongue, gingiva, gingiva buccal complex, soft and hard palate, and floor of the mouth. Tongue cancer was common cancer in all the studies included [Graph 1]. Mostly T2 and T4 stages in TNM staging were found in these studies [Graph 2]. The 14 studies which were included in systematic review are enlisted in [Table 2]. Among these studies, 13 studies were prospective and 1 study was both prospective and retrospective. Lymph node metastasis was unit analysis. CT studies were done with contrast enhancement. Two MRI studies (Punhani et al.^[9] in 2017 and Goel et al.^[11] in 2016) used T1W and T2W fast spin echo sequence along with short tau inversion recovery sequence and diffusion-weighted imaging (DWI) where ADC value was calculated respectively. For MRI, the sensitivity ranged from 33%–94.4% and specificity ranged from 96%–100%. DW MRI study showed a better sensitivity (94.44%), specificity (96%), and diagnostic accuracy (95.08%) of lymph node metastasis when compared with the other two studies. Among 12 studies done in contrast-enhanced CT (CECT, the range of sensitivity was 11% to 92%, specificity was 42% to 100% and diagnostic accuracy was 61% to 96.1%. Mishra et al.^[16] 2016 study among CECT gave a highest accuracy of 96.1%.

Figure 2: Study characteristic of the included studies in systematic review. CT - Computed tomography and MRI - Magnetic resonance imaging

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Table 2: Study characteristics and included data sets for computed tomography and magnetic resonance imaging of the included studies

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Quality of included studies

All the studies had fairly good applicability. For risk of bias assessment, five studies (Suryavanshi et al.,^[10] 2021; Sharma et al.,^[12] 2018; Kallalli et al.^[15] 2016; Mishra et al.,^[16] 2016; and Chaukar et al.,^[18] 2016) had a low risk of bias, two studies (Punhani et al.,^[9] 2017, and Sharma and Agarwal et al.,^[19] 2021) had a high risk of bias, and seven studies (Tuli et al.,^[6] 2008; Pandeshwar et al.,^[7] 2013; Bakshi et al.,^[8] 2015; Goel et al.,^[11] 2016; Geetha et al.,^[13] 2010; Hallur et al.,^[14] 2021; and Shetty et al.,^[17] 2015) had an unclear risk of bias [Table 3].

Quantitative assessment

Meta-analysis

Meta-analysis was done for 8 studies out of 14 studies. Six studies which had considerable amount of heterogeneity and lack one or more variables of TP, TN, FP, FN were not included. In these 8 articles, 7 studies were CT and 1 study in MRI. The summary of sensitivity and specificity of CT and MRI in diagnosis of lymph node metastasis were analyzed using RevMan software (2014) and forest plot with the confidence interval 95% (CI = 95%) was derived [Figure 3]. Among the studies, Geetha et al.,^[13] 2010, had the most skewed distribution with sensitivity 50% (95% CI: 12%88%), while the specificity was 100% (95% CI: 40%100%). Other studies had moderately skewed distribution such as Abishek Sharma et al.,^[12]2018, having sensitivity 90% (95% CI: 55% to100%) and specificity 88% (95% CI: 75% to 95%), Chaukar et al.,^[18] 2016, had sensitivity of 76% (95% CI: 59% to 88%) and specificity 85% (95% CI: 72% to 94%), Pandeshwar et al.,^[7] 2013, showed sensitivity of 92% (95% CI: 74% to 99%) and specificity was 84% (95% CI: 64% to 95%), Sharma et al.,^[9]2021, had a sensitivity of 92% (95% CI: 75% to 99%) and specificity of 43% (95% CI: 28% to 59%); Hallur et al.,^[14] 2021, showed a sensitivity of 67% (95% CI: 35% to 90%) and specificity of 90% (95% CI: 81% to 95%). One study by Mishra et al.,^[16] 2016, showed homogeneous distribution and good sensitivity and specify of 87% (CI: 68% to 98%); 97% (CI: 93%99%); Punhani et al.^[9]2017, which was a MRI study had a sensitivity of 75% (66% to 100%) while specificity was low as 100% (CI: 6% to 61%).

Figure 3: Forest plot showing overall sensitivity and specificity of CT and MRI studies included for meta-analysis

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The sensitivity values obtained from these 8 studies were plotted in ROC curve with sensitivity in X-axis and specificity in Y-axis. It revealed a sensitivity of 92% and specificity of 70% for CT and sensitivity of 75% and specificity of 91% for one MRI study, their corresponding values were identified in ROC curve in detecting the cervical lymph node metastasis [Graph 3].

Discussion

Oral squamous cell carcinoma is a common malignancy of head and neck leading to lymph node metastasis. Cervical lymph node status at the time of diagnosis is one of the most important factors affecting the long-term survival of the patient. Identification of sentinel lymph node, occult metastasis, and skip metastasis is very important in the prognosis of the patient. Cancer cells get disseminated and reach the nearby lymph node through lymphatic drainage and change to metastatic node. The first lymph node in a regional lymphatic basin that receives lymph flow from the primary tumor is called sentinel node. This provides a “road map” of the lymphatic drainage from a tumor site. Normal “lima beam” shape of lymph node changes to round shape on metastasis and there will be increase in size, conglomeration of nodes occur and gets fixed to underlying structures.^[2] These can be evaluated by clinical palpation although there will be still metastatic nodes without showing these features. Hence, imaging these nodes draining the area of cancer is essential.

Since 1981, CT has been used to determine neck metastasis in head-and-neck cancer. CT with hard and soft tissue window can delineate the primary tumor, distance metastasis as well as lymph node metastasis. CECT is most commonly used for the purpose of viewing tissues in deeper planes, vascular supply, and the disease extent. Disadvantage of CECT is high cost, radiation exposure, and risk of anaphylaxis due to intravenous contrast and it cannot be repeated every time. Geetha et al.^[13] in 2010 in their study using CT found 3 TP and 3 FN nodes which resulted in sensitivity of CT to 50%. In this study, it was found that size criteria were more reliable for small nodes and rim enhancement with central necrosis is highly specific indicator of metastasis for large nodes. Kallalli et al.^[15] in 2016 and Mishra et al.^[16] in 2017 are similar study to Geetha et al.^[13] with 20 and 30 patients, respectively. Their sensitivity of CT was 81% and 86.7%, respectively, which may be due to sample size and criteria used for diagnosis. Mishra et al.^[16] found to have the highest accuracy (96.1%), very low risk of bias, and homogeneous distribution of data in our study.

MRI provides better resolution of detailed soft tissue architecture than either CT or ultrasonography (USG), especially in 3D visualization of the soft tissue lesions and nodal metastasis. The use of MRI, in the head-and-neck region, is supported by the fact that orofacial tissues have a variable amount of fat distribution in different regions. Hence, different sequencing will aid in the viewing of tumor site, extent, and characteristics ideally.^[21] Moreover, MR imaging is free from metal streak artifacts caused due to dental restorations as seen on CT images. Diffusion-weighted MRI (DW-MRI) is superior in detecting nodal metastasis.^[21]. Diffusion-weighted image (DWI) is a non-invasive functional technique to study the molecular function and microstructure of the tissue and lesion. Apparent diffusion coefficient (ADC) mapping using signal intensity in DWI is based on the analysis of water molecule motion.^{[21],[22],[23]} This is used to differentiate benign and malignant nodes. Goel et al.^[11] in their study showed the ADC cutoff value between benign and malignant nodes as 1.39 × 10-³ ^mm2/s. However, Amit et al. in 2019^[21] made a prospective study in patients with lymphadenopathy and found an ADC cutoff value of 0.93 × 10⁻³ mm²/s. The major limitations of MRI include its reduced availability and difficulties in performing MRI scan in patients who are claustrophobic and uncooperative. MR imaging is contraindicated in patients who have pacemakers and vascular clips.^[20],[23] Both CT and MRI have their own advantages and disadvantages, but they still remain the reliable modality for investigation and treatment planning in oral cancer patients.

Key criteria for identification of metastatic lymph node in computed tomography and magnetic resonance imaging

In our systematic review and meta-analysis, we have comprehensively evaluated all the evidence from 14 studies, and there were variable diagnostic criteria used for CT and MRI. With respect to good sensitivity, specificity, and diagnostic accuracy, we derive a common holistic criterion for CT and MRI for identifying a metastatic lymph node, which are as follows:

Size of the node >10 mm in all the levels except IB and IIA (>15 mm)
Round or spherical shape long-axis/short-axis (L/S) ratio ≤2
Irregular border of lymph node
Arterial invasion is noted by the degree of obliteration of the normal fat plane surrounding the artery
Heterogeneity density of node
Enhance periphery with central hypointense area of central necrosis,
Grouping of three or more nodes, each of 815 mm diameters, which are contiguous
Extranodal tumor extension seen as thickened nodal rim with infiltration of adjacent fat planes.

Our meta-analysis has pooled the results from 14 studies and found that CT had good sensitivity and MRI had good specificity which was in accordance with similar studies done by Sun et al.^[24] in 2015 and Park et al.^[25] in 2020 in their systematic review and meta-analysis. De Bondt et al.,^[26] in 2007, evaluated the diagnostic performance of USG-guided fine-needle aspiration cytology (USG-FNAC), USG, CT, and MRI and found that USG-FNAC is the most reliable imaging technique for identifying metastases in cervical lymph nodes in head-and-neck cancer patients. This variation may be due to size and shape of lymph node were only taken into consideration to determine whether a node is pathognomonic. Similar to our systematic review and meta-analysis comparing CT and MRI for lymph node metastasis, studies have been done for uterine cancer by Bipat et al.^[27]in 2003 and cervical cancer Bin Liu et al.^[28] in 2017 and they concluded that MRI showed better modality for identifying lymph node metastasis than CT, especially DWI sequence. However, Cho et al.^[29] in 2020 for thyroid cancer in their review and meta-analysis exclusively for MRI reported that MRI showed moderate diagnostic performance in the diagnosis of metastatic lymph nodes in patients with thyroid cancer in the neck, but this may be due to all studies which were included seemed to be retrospective and there was a high risk of bias.

Finally, irrespective of CT or MRI, the imaging diagnosis of metastatic lymph node were based on size, shape (L: S > 2), central necrosis with peripheral rimming as criteria. Studies done in 2021 had additional criteria as the extra nodal extension (ENE), this is included in the revised 8th edition AJCC staging of head-and-neck cancer.^[30]

Limitation of the study

The limitations of our study, first, although we conducted a meta-analysis, the studies showed that assessed variables largely did not account for heterogeneities between studies. Second, the present study was focused on the only group of Indian population, hence more MRI studies in order to evaluate its diagnostic accuracy in detection lymph node metastasis in oral cancer among Indian population are needed. Thus, we will be able to narrow down the promising diagnostic study. Finally, with more sample size and homogeneous data, we will be able to analyze CT and MRI independently for diagnostic accuracy is also required.

Conclusion

Our comprehensive systematic review and meta-analysis have identified that both CT and MRI show reasonable diagnostic performance for detection of cervical lymph node metastasis in oral cancer patients in India. Our study seems to be one of the first of its kind exclusively in Indian population. In our study, CT has a good sensitivity which is essential to investigate metastatic node. Nevertheless, MRI with good specificity is needed for diagnostic confirmation or eliminates nonmetastatic nodes. This is essential for selective neck dissection which influences the morbidity and mortality in patients. The lymph node size, shape, and structural changes such as central nodal necrosis and peripheral rim with infiltration into adjacent fat (ENE) are diagnostic markers of metastasis. Further, more research and literature are to be drawn in this spectrum for more adequate and valuable information on primary or metastatic oral cancer.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Disclosure

This material has never been published and is not currently under evaluation in any other peer reviewed publication.

Ethical approval

The permission was taken from Institutional Ethics Committee prior to starting the project. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Not applicable.

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