Liao et al. BMC Cancer 2012, 12:236 http://www.biomedcentral.com/1471-2407/12/236 Background Lymph node status is one of the most important pre- dictors of poor prognosis in head and neck cancers. For patients with clinically positive (cN+) neck lymph node metastasis, modified radical neck dissection is a standard procedure. For patients with clinically nega- tive (cN0) neck, there are two major management strategies, which include elective neck dissection or a “watchful waiting policy”. Cervical lymph node metas- tasis staged by palpation has been demonstrated to be inaccurate; the rate of occult cervical nodal metastases is at least 30% by simple palpation [1]. To avoid the unnecessary treatment of histologically negative necks, a staging technique must be sensitive enough to re- duce the risk of occult metastases to less than 20%, which means a negative predictive value (NPV) of more than 80% [2,3]. Bayesian logic states that the probability of a disease being present given that a test is negative depends on the pre-test probability or the prevalence of the disease, and the sensitivity and spe- cificity of the test can be described by the following formula [4]: Negative predictive value ¼ specificity ð1 prevalenceÞ =½specificity ð1 prevalence þð1 sensitivityÞ prevalence With the development of modern imaging modalities, the American Joint Committee on Cancer has stated that clinical staging should include physical examination as well as the results of other imaging modalities. Research is now directed toward finding a staging method sensi- tive enough to bring the risk of occult metastases below 20%. Previous meta-analyses [2,5] compared the diagnos- tic accuracy of different imaging modalities in neck node evaluation. However, these studies looked at a mixture of cN + and cN0 patients, and no study has focused only on patients with cN0 necks. The aim of this study was to complete a systematic review for the performance of dif- ferent imaging modalities, i.e., computed tomography (CT), magnetic resonance imaging (MRI), positron emis- sion tomography (PET) and ultrasound (US), in the evaluation of neck lymph node metastasis in clinically N0 head and neck cancer patients. Methods Literature search A computerized systematic literature search was per- formed by one reviewer (Liao LJ). Abstracts were selected for English articles reporting on diagnostic per- formance in the detection of lymph node metastasis in head and neck cancers. The search strategy used text and relevant indexing to capture the concept of Page 2 of 7 ultrasonography in head and neck cancer patients with N0 neck evaluations. PubMed (up to May 2011) and CENTRAL (via the Cochrane database up to October 2010) were searched using the following keywords: (a) (Head and Neck Neo- plasms[MH]) NOT (Thyroid Neoplasms[MH] OR Esophageal Neoplasms[MH] OR Nasopharyngeal Neo- plasms[MH] OR Salivary Gland Neoplasms[MH] OR Melanoma[MH] OR Parathyroid Neoplasms[MH]); (b) Diagnostic imaging[MH]; (c) lymph node[TW] OR neck node[TW]; and (d) sensitivity[TW] OR accuracy[TW]. Human studies with abstracts in English were included. Reviews, letters to the author, comments and case reports were excluded. From the selected abstracts, two reviewers (Lo WC and Wang CT) separately screened the full text of these potentially eligible articles in which computed tomog- raphy (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and ultrasound (US) were utilized. Reference lists were manually screened for add- itional relevant articles. Inclusion criteria There were two major study groups according to the clinical node staging of the patient population in each study. The first group included studies of patients who had pathologically positive head and neck cancer and clinically negative cervical lymph nodes (cN0) before the imaging examination. The second group included studies with mixed patient populations (head and neck malig- nancy with both cN0 and cN+). We included studies with individual patient data available for cN0. Based on the full text reports, studies were selected if they fulfilled all of the following inclusion criteria: (a) histopathology findings for neck dissection (specimens obtained at surgery) or sufficient follow-up time were used as the reference standard; (b) the primary tumor and lymph node metastases were squamous cell carcin- omas (SCCs); and (c) sufficient data were presented to construct a 2 × 2 contingency table (sensitivity and/or specificity with absolute numbers of false positive (FP), false negative (FN), true positive (TP) and true negative (TN) findings) for the imaging modalities compared using the reference standard. Exclusion criteria Studies were excluded if raw data were not presented. We also excluded studies with both cN0 and cN positive patients, where individual data for cN0 patients were not available. Quality assessment of primary studies The Quality Assessment of Diagnostic Accuracy Studies (QUADAS)[6] quality assessment tool was used to