The purpose of this systematic review was to answer the clinical question “When should elective neck dissection be performed in maxillary gingival and alveolar squamous cell carcinoma with a cN0 neck?” A systematic review, designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, was conducted by two independent reviewers with three rounds of search and evaluation. Ten studies with 506 patients were included in the final review. The overall risk of cervical metastasis was 23.2% for those who did not receive an elective neck dissection (END), which was 3.4 times higher than that in the END group (6.8%). The 5-year survival rate was higher in those who had an END (80.3%) when compared to those who did not receive an END (67.4%). Overall, 14.1% of the cases with cN0 maxillary squamous cell carcinoma (SCC) presented with positive node(s) in pathological specimens after END. The risk of occult cervical metastasis in a cN0 maxillary SCC case with pathological stage pT1, pT2, pT3, and pT4 was 11.1%, 12.1%, 20%, and 36.1%, respectively. It is therefore concluded that END is recommended in patients with cN0 maxillary SCC, especially in stage T3 or T4 cases.
Cervical metastasis of squamous cell carcinoma (SCC) in the oral cavity is common and may require neck dissection with resection of the primary tumour for the clearance of all tumour cells. Cervical metastasis may be clinically apparent, or can present as occult metastasis that is not noticeable clinically at the time of disease staging. Elective neck dissection (END) may be performed when the chance of occult metastasis is high. Traditionally, END has been employed as a part of the treatment plan for tumours with risks of more than 20% of occult metastasis to have better neck control.
Maxillary SCC is a less-studied carcinoma in regards to its need for END for cases with no clinical cervical node metastases or cN0, due to its lower occurrence compared to other carcinomas in the head and neck region. The ‘cN0’ referred to in this review relates to the patient who has undergone clinical examination and various imaging investigations, including radiographic examination, ultrasound, computed tomography (CT), and/or magnetic resonance imaging (MRI), as mentioned by the authors of the studies included, and the patient was found to have no neck nodes on clinical examination and various imaging techniques. There are few studies on the control rate achieved by END in maxillary SCCs because the survival rate, recurrence, and metastases of these tumours are not well established.
It is important to make an evidence-based clinical judgement regarding when to do an END on a patient with maxillary SCC and a clinically negative neck (cN0). However, thus far there is no consensus and no guideline criteria for this clinical entity. The aim of this study was therefore to conduct a systematic review to answer the clinical question “When should elective neck dissection be performed in maxillary gingival and alveolar squamous cell carcinoma with a cN0 neck?” The objectives of this systematic review were to assess the treatment outcomes including survival rates and occult cervical metastases of maxillary SCC with cN0 with or without END, in order to provide evidence as to the indications for performing an END in the patient with maxillary SCC with cN0.
Materials and methods
This systematic review was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Two rounds of comprehensive searches and an evaluation round were performed to search the available literature for relevant articles related to the clinical question. Both authors served as reviewers for the three rounds.
First round search
The first round search was an electronic search of databases including Ovid MEDLINE, PubMed, and Cochrane Library, with the following Keywords [“maxilla” OR “maxillary”] AND [“squamous cell carcinoma”] AND [“survival” OR “recurrence” OR “metastasis”]. There was no language restriction. The last search date was 28 February 2015. The titles and abstracts of the articles found were reviewed by the two reviewers. Articles that were relevant to the treatment outcomes of maxillary SCC with cN0 were obtained. For those studies that appeared to be relevant but for which there was insufficient information in the abstract, the full text of the article was collected for further review. Relevant articles selected in the first round were submitted to the second round.
Second round search
The second round search consisted of a manual search and a reference list search. The manual search was performed in three international journals on the subject of oral and maxillofacial surgery, covering a 10-year period (February 2005 to February 2015); these journals were the International Journal of Oral and Maxillofacial Surgery , Journal of Oral and Maxillofacial Surgery , and British Journal of Oral and Maxillofacial Surgery . A reference list search was performed of the reference lists in the articles included from the first round. Relevant articles that were not included on the list from the electronic search were obtained and reviewed by the two reviewers. Any relevant articles, along with those from the first round search, were entered into the third round.
Third round evaluation
The articles identified were evaluated against the following six criteria: (1) the study included patients diagnosed with primary maxillary SCC with cN0 (including maxillary gingiva, alveolus, and palate; excluding maxillary sinus and nasal cavity); (2) the study included patients who had not undergone other treatment prior to the study; (3) the study included patients with no distant metastasis; (4) the study included tumour resection with or without END as the treatment for the disease; (5) the postoperative follow-up period (at least 3 years) was described clearly, with information on recurrence, metastasis, and the survival rate of the treated patients; (6) the study had a sample size of at least 10 patients.
Articles that fulfilled all six criteria were selected to enter the final review. The reasons for exclusion of the rejected articles were recorded.
Data collection process
The following demographic data and surgical outcomes of the studies included in the final review were extracted: authors, year of publication, study design, number of patients in the study, male to female ratio, mean age of patients, follow-up period in months, number of cases receiving an END and number undergoing observation (without END), incidence of cervical metastasis, overall 5-year survival rate, percentage of pathological positive lymph nodes (pN+) in patients with cN0 who had undergone END, and the percentage of cervical metastasis in relation to pathological T staging (pT).
The collected data were analyzed. Analyses of cervical metastasis and the overall 5-year survival rate of the maxillary SCC patients were performed. The percentage of positive pathological lymph nodes (pN+) in patients with cN0 who had undergone END was analyzed. Furthermore, the percentage of cervical metastasis in relation to the pathological T stage (pT) was assessed and analyzed.
Risk of bias assessment
In order to assess the risk of bias in the studies included in the final review, a methodological quality assessment that includes five items was applied; these items were random selection, defined inclusion/exclusion criteria, reported loss of follow-up, validated measurement, and statistical analysis. This assessment was constructed by combining the proposed criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) checklist, and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. A study that met all five criteria mentioned was categorized as having a ‘low risk’ of potential bias, whereas a study that did not meet one of the five criteria was considered to have a ‘moderate risk’ of bias. When a study did not meet two or more of the criteria, that particular study was placed in the ‘high risk’ of bias category.
A total of 679 articles were identified through the search strategy used in the electronic search. Of these, 25 articles were found to be relevant to the treatment outcomes of maxillary SCC with cN0. The manual journal search and reference search yielded no extra articles. After the third round evaluation process applying the six criteria, 10 articles were found to be eligible for the final review. The 15 articles that were excluded are listed in Table 1 , with the reasons for their exclusion. A flow diagram of the article selection process is presented in Fig. 1 .
|Year||Authors||Title||Study type||Reason for exclusion|
|2004||Smith et al.||Management of the neck in patients with T1 and T2 cancer in the mouth||Retrospective||There was only one case of hard palate SCC included in the study|
|2005||Umeda et al.||En bloc resection of the primary tumour and cervical lymph nodes through the parapharyngeal space in patients with squamous cell carcinoma of the maxilla: a preliminary study||Retrospective||No mention of END and its clinical outcomes|
|2008||Kessler et al.||Neoadjuvant and adjuvant therapy in patients with oral squamous cell carcinoma: long-term survival in a prospective, non-randomized study||Non-randomized prospective||No cases of maxillary SCC included in the study|
|2008||Binahmed et al.||Treatment outcomes in squamous cell carcinoma of the maxillary alveolus and palate: a population-based study||Retrospective||Insufficient data on END and observation with its respective outcomes|
|2008||Kermer et al.||Surgical treatment of squamous cell carcinoma of the maxilla and nasal sinuses||Retrospective||No patients with cN0 included in the study|
|2009||Ferlito et al.||Elective management of the neck in oral cavity squamous carcinoma: current concepts supported by prospective studies||Literature review||A literature review article with no data mentioned on maxillary SCC with cN0|
|2010||Valentini et al.||Management of clinically negative neck in maxillary carcinoma||Retrospective||No mention of END and its outcome|
|2010||Wang et al.||Risk factors affect the survival outcome of hard palatal and maxillary alveolus squamous cell carcinoma: 10-year review in a tertiary referral centre||Retrospective||No mention of occult cervical metastasis rate and survival rate in relation to END group patients|
|2011||Poeschl et al.||Staging and grading as prognostic factors in maxillary squamous cell carcinoma||Retrospective||Only eight patients with cN0 included in the study and no mention of END|
|2011||El-Naaj et al.||Incidence of oral cancer occult metastasis and survival of T1–T2N0 oral cancer patients||Retrospective||Only one case of tumour of the palate included in the study|
|2012||Beltramini et al.||Is neck dissection needed in squamous-cell carcinoma of the maxillary gingiva, alveolus, and hard palate? A multicenter Italian study of 65 cases and literature review||Retrospective||No data on survival in relation to END and observation group|
|2013||Kumar et al.||Cancers of upper gingivobuccal sulcus, hard palate and maxilla: a tertiary care centre study in North India||Retrospective||No mention of END and its outcome|
|2014||Sagheb et al.||Cervical metastases of squamous cell carcinoma of the maxilla: a retrospective study of 25 years||Retrospective||No mention of END and its outcome|
|2014||Aydil et al.||Neoplasms of the hard palate||Retrospective||No cases of maxillary SCC included in the study|
|2014||Bobinskas et al.||Influence of the site of origin on the outcome of squamous cell carcinoma of the maxilla—oral versus sinus||Retrospective||No mention of cN0 patients and END in the study|
Characteristics of the studies included
The features of the studies included in the review are presented in the Table 2 . All 10 articles related to retrospective studies. There were 506 patients with maxillary SCC with cN0 included in the 10 studies; of these patients, 206 received an END (either selective neck dissection or modified radical neck dissection; END group) and 300 patients did not receive an END and were observed for any recurrence or metastasis of the SCC after tumour resection (observation group). There was no consensus type or level of END in the studies included, as for each study this was done at the discretion of the treating surgeon. In the study by Poeschl et al., the END group patients underwent only selective neck dissection from level I to level III, whereas in the study by Feng et al., the END group patients underwent various types of neck dissection, including unilateral supraomohyoid neck dissection (level I, II, or III), extended supraomohyoid neck dissection (level I, II, III, or IV), modified radical neck dissection, and bilateral supraomohyoid neck dissection.