The present study investigated the diagnostic value of conventional WLE, NBI endoscopy and Lugol's iodine staining under WLE (endoscopic iodine staining) in the screening and early diagnosis of nasopharyngeal carcinoma. There were no significant differences in the diagnostic performance of conventional WLE, NBI endoscopy or endoscopic iodine staining for differentiating nasopharyngeal carcinoma and chronic hyperplastic nasopharyngitis. The diagnostic performance of the combination of conventional WLE, NBI endoscopy and endoscopic iodine staining was significantly improved compared to any method alone.

Current screening methods, including EBV antibody test, CT/MRI, positron emission tomography scan, conventional white light nasopharyngoscopy, and NBI endoscopy, can improve early diagnosis of nasopharyngeal carcinoma. Conventional WLE is commonly used in endoscopic examinations of nasopharyngeal carcinoma. However, conventional WLE does not detect subtle changes in morphology or mucosal blood vessels in the nasopharyngeal region, and WLE cannot differentiate between nasopharyngeal carcinoma and chronic nasopharyngeal mucosal inflammation based on color and morphologic (apophysis or anabrosis) abnormalities [10]. This can lead to misdiagnosis and missed diagnosis of nasopharyngeal carcinoma.

NBI is an endoscopic technique that uses filters to illuminate the mucosa with light from selected bands (415 nm, blue light; 540 nm, green light) of the optical spectrum. The filtered light preferentially enhances the mucosal surface and the network of superficial blood vessels [11]. NBI endoscopy can identify intrapapillary capillary loops (IPCLs) in stratified epithelium, which are destroyed and replaced by irregular neo-tumor vasculature. NBI endoscopy is limited by a number of factors, including the presence of mucus, blood and keratin that can significantly interfere with the interpretation of NBI features [12]. NBI endoscopy is widely used in the diagnosis of head, neck, throat and hypopharyngeal lesions, and there are multiple NBI endoscopic classifications based on vascular changes for different organs [13]. A NBI classification of nasopharyngeal mucosal microvessels has been developed to facilitate differential diagnosis of benign and malignant lesions of the nasopharyngeal region (Types I-IV benign, Type V, malignant). Previous studies based on this classification suggest the sensitivity and specificity of NBI endoscopy for nasopharyngeal lesions are higher than conventional WLE [14]. The sensitivity, specificity, accuracy, PPV, and NPV for distinguishing nonmalignant from malignant lesions were 97.4%, 84.6%, 92.7%, 91.6%, and 95.1%, respectively, for patients with pharyngolaryngeal lesions, 98% of histologically malignant lesions corresponded to a type V pattern, and 84.8% of non-neoplastic lesions corresponded to a type I to IV pattern [15]. The characteristics of nasopharyngeal carcinoma under NBI endoscopy mainly appeared as a type V pattern (79.5%, 167/210), and the sensitivity, specificity, PPV, and NPV of type V in the diagnosis of nasopharyngeal carcinoma were 79.5%, 91.3%, 96.0%, and 62.9%, respectively, in patients with a suspected nasopharyngeal tumor. NBI endoscopy significantly improved the detection of superficial lesions (χ2 = 12.789, p < 0.0001) compared to WLE [16]. The sensitivity and NPV of NBI endoscopy for nasopharyngeal carcinoma screening were significantly higher than those of WLE (93.9% vs 71.2%, P = 0.001; and 98.1% vs 91.7%, P = 0.003; respectively) in consecutive patients at high risk for nasopharyngeal carcinoma. The presence of superficial, distorted, irregularly shaped microvessels on NBI endoscopy indicated malignant lesions [17].

Endoscopic iodine staining with Lugol's iodine is widely used in head and neck endoscopy and can assist in delineating normal and abnormal margins, informing endoscopic resection [18]. Lugol's iodine stains glycogen in normal squamous epithelium, which appears brown under WLE. In glycogen depleted epithelium such as dysplasia, the mucosa appears yellow or unstained [19]. Knowledge of head and neck anatomy is necessary when interpreting Lugol’s staining of nasopharyngeal lesions. The attached gingivae and hard palate, which are heavily keratinized, and the respiratory mucosa, which does not contain glycogen, do not stain with Lugol’s iodine [20]. The glycogen containing cells lining the oral cavity and oropharynx do stain [21] Endoscopic iodine staining is limited by the presence of blood and allergic reactions to Lugol’s iodine, including laryngospasm, bronchospasm, and cardiac arrest. High concentrations of Lugol’s iodine may result in large amounts of free iodine, which can cause mucosal damage [20]. Spraying Lugol’s iodine solution in the pharynx is associated with heartburn, severe discomfort, and risk of aspiration [22]. In the present study, according to previously published literature, 1.5 ml of a 1.6% iodine solution was sprayed from the top of the nasopharynx [7] with few adverse effects. Timing of the interpretation of endoscopic iodine staining is subjective and requires a certain amount of clinical experience. In patients with suspected esophageal cancer, the appearance of a color change (designated as a pink-color sign [PCS]) within 1 min after Lugol’s iodine staining had a higher diagnostic performance (sensitivity, 90.2%; specificity, 82.3%; diagnostic accordance rate of 88.6%), than appearance of a PCS at 2 min (sensitivity, 84.1%; specificity, 72.7%; diagnostic accordance rate of 79.7%) [23]. The rapid appearance of PCS seems to indicate a high degree of epithelial destruction. The timing of the appearance of PCS was significantly and independently associated with high-grade intraepithelial neoplasia/invasive cancer. In the present study, patients were seated and excess iodine solution was removed by coughing or blowing the nose. Reexamination was performed 1 min after spraying with Lugol’s iodine solution.

A previous report showed that NBI endoscopy combined with endoscopic iodine staining may be beneficial for the diagnosis of esophageal cancer and precancerous lesions. Similarly, our findings suggest the diagnostic performance of the combination of conventional WLE, NBI endoscopy and endoscopic iodine staining for discriminating between nasopharyngeal carcinoma and chronic hyperplastic nasopharyngitis was significantly improved compared to any method alone. Importantly, NBI endoscopy and endoscopic iodine staining alone or combined had a high NPV for nasopharyngeal carcinoma, implying these methods may identify patients with a high probability of no clinically significant cancer that may avoid unnecessary biopsy and surgeries. This indicates that NBI endoscopy and endoscopic iodine staining may have clinical utility for selecting patients with nasopharyngeal lesions that are eligible for a watch-and-wait strategy.