A study on the value of narrow-band imaging (NBI) for the general investigation of a high-risk population of nasopharyngeal carcinoma (NPC)

Nasopharyngeal carcinoma (NPC) is a common malignant head and neck tumor [1]. It has been verified by studies that the 5-year survival rate of NPC can reach up to 90% [2], and the main reason for treatment failure of advanced NPC lies in the distant metastasis [3, 4]. Hence, the most effective approach to enhance the long-term therapeutic effect of NPC is early diagnosis and treatment, and early diagnosis is the necessary condition to early treatment. Through testing for peripheral blood Epstein-Barr (EB) virus antibodies, the high-risk population of NPC could be screened out and undergo nasopharyngeal examinations. For subjects with abnormities, biopsies were conducted. When subjects were pathologically diagnosed with NPC, they are treated accordingly. General NPC investigation covers two key points: (1) in serological screening, the high-risk population of NPC was screened out via the EB virus antibody test [5], and (2) in diagnosis screening, the high-risk population of NPC underwent nasopharyngeal examinations [6]. During the screening, biopsy rate was higher, while positive pathology rate was lower. This was because the anatomical position of the nasopharyngeal region is relatively deep, nasopharyngeal mucosal inflammation tends to occur, and the mucosal appearance is not smooth. Part of these NPCs was of submucosal type. Furthermore, standard endoscopic examination revealed that the mucosal lesions were not clear, and no biopsy position was identified, which lead a lower diagnosis rate of the biopsy. At present, the WL mode is commonly used in endoscopic examinations. In white light mode (WL), nasopharyngeal masses are considered positive [7]. However, no subtle changes in nasopharyngeal mucosal blood vessels are likely to be observed, which has adverse effects on diagnostic screening results. Narrow-band imaging (NBI) can display these abnormal subtle submucosal vessels [8]. The novel endoscopic findings in nasopharyngeal carcinoma (NPC) under narrow-band imaging (NBI) were as followed: brownish spots, irregular microvascular pattern (IMVP), light crests, and side-difference. Hence, it can increase the diagnostic rate of subtle lesions or superficial lesions. Since 2011, our department has applied NBI for NPC diagnosis and has presented satisfactory effects [9]. Moreover, other scholars have carried out studies on head and neck carcinomas and verified that NBI outmatches common approaches [10‐12]. However, studies on NBI focused on outpatients or inpatients [13], and the majority of the existing general investigations are mainly applicable to indirect pharyngorhinoscopy or hard-tube pharyngorhinoscopy. In addition, literature on general NPC investigations have rarely reported on NBI. Therefore, this technology was applied to the diagnostic screening of a high-risk population of NPC, in order to explore the role of NBI in general investigations. The results are reported below.

Being endemic in South China, the five-year survival rate of early-stage NPC can reach up to 89.7% [16], while that of middle-late stage NPC decreased to 75% [17]. For the steps of the general NPC investigation, through EB virus serological screening, the high-risk population of NPC was identified, and cases with NPC were diagnostically screened out. In this study, a follow-up by microscopy was carried out according to the above steps, and biopsy was carried out for the population with abnormalities determined by microscopic examination. Previously, WL mode endoscopic systems such as the nasal endoscope, fiber, or electronic nasopharyngolarygnoscope were adopted to carry out the diagnostic screening of NPC. It is relatively difficult to display the subtle vessels of the nasopharyngeal mucosa by the WL mode endoscopic system, which led to failure in the recognition of subtle changes in vessels. This resulted to ① the misdiagnosis of the nasopharyngeal micro-carcinoma and ② the low diagnosis rate of nasopharyngeal biopsy due to difficulty in distinguishing nasopharyngeal inflammatory neoplasms from cancerous lesions. NBI can filter out the red light with the longest wave in the common white light through the narrowband light filter, and the green light and blue light of the narrowband spectrum can be reserved. The hemoglobin in submucosal vessels can absorb much more green light and blue light for the optical property. Thus, the contrast ratio between the mucosal epithelia and submucosal vessels would increase, which is conducive for identifying the morphologic changes of the tumor vessel.

In current literature, under the WL mode, 115 cases were diagnosed with abnormities, in which 19 cases were diagnosed with NPC, which was significantly more than that under the NBI mode (24 cases). This indicates that these 115 cases received nasopharyngeal biopsy under the WL mode. This was familiar with that of a previous study, where the nasopharyngeal endoscopy coupled with NBI was able to provide a rapid, convenient, and highly reliable screening for high-risk populations [18]. Few literature have reported the indications and standards of biopsy. Xu S et al. [19] believed that the diagnosis rate of biopsy under the nasal endoscope is higher than that through the oral cavity, but the specific indications of the biopsy were not mentioned. Different from microscopic examinations, a biopsy holds the advantage of identifying the diagnosis; while its disadvantages mainly include infection, hemorrhage and cancer cell detachment, and implantation metastasis due to the traumatic examination. Therefore, biopsy may lead to bleeding in patients with coagulopathy [20]. In the present data, color abnormity and morphologic abnormality were regarded as biopsy indications, and it was found that the rate of the two indications above in mucosal inflammation exceeded 50%. Hence, at present, there is an urgent need to seek for an effective method to guide the inclusion criteria for nasopharyngeal tissue biopsy.

Some research indicated that [21, 22] early-stage tumors tend to be accompanied with changes in mucosal superficial vascular structures such as the vascular morphology changes and morphology changes of new vessels. Similar to the above research results, in the present data, the increase rate, expansion rate, and morphologic abnormality rate of these blood vessels with NPC were all significantly more than those of the chronic inflammation of the nasopharyngeal mucosa. Based on such change in the early stage of tumors, during the application of NBI, mucosal vessels are revealed through blue and green light, and mucosal tissues and blood vessel morphologies are emphasized by means of optical imaging emphasis technology. This can improve the contrast performance of the images and increase the differential diagnosis rate. It has been reported by studies that the NBI endoscopic system was applied to the early diagnosis and differential diagnosis of other malignant tumors [16, 17]. Recently, it was reported that NPC diagnosis by NBI has been carried out in clinical and relevant fundamental studies [21‐23]. All results verified the significance of NBI in NPC diagnosis. In previous studies, similar conditions were reached [9]. Under the NBI mode, the diagnosis accordance rates of cases with stage I and II NPC were 100.0% (5/5) and 85.7% (6/7), respectively, which were significantly higher than those under the WL mode (− 0 and 14.3% [1/7]), and the overall diagnosis accordance rate under the NBI mode was 93.0%. Subsequently, Madana et al. [23] verified by research that the NBI mode was superior to the WL mode, because NBI can display tumor vessels better. In the present data, vascular morphologic abnormality under the NBI mode reached up to 82.61%. Compared with the common WL mode endoscope, the endoscopic system with the NBI mode can freely switch over to the two modes once without placement of another endoscope. In this study, the NBI HD endoscope was applied for the general investigation, and the consistency with the biopsy pathology results was very satisfactory (kappa coefficient = 0.973). Moreover, sensitivity, specificity, and the area under the ROC curve were significantly superior to those under the WL mode; and the expenses were lower than that under the WL mode. Ni XG et al. [24] also obtained similar results, in which sensitivity, specificity, predicted positive value, and predicted negative value during the NBI endoscopy of the NPC were 80.6, 91.7, 96.7, and 61.1%, respectively. The present corresponding data were slightly higher than those above, and 2011–2012 levels were obtained (0.93). It is inferred that the above results are correlated with the increase in cases, which further accumulated and promoted experience. Different from other scholars, our group data was mainly applied to diagnostic screening and the number of examinations was greater. At present, few literature have reported that NBI technology can be applied to general NPC investigations. At present, due to the varied positive differences of the nasopharyngeal NBI mode [25], we consider that abnormal symptoms include disordered texture of the superficial vessels of the mucosa, local circuitry, intensively distributed punctiform vessels, and lumbriciform or rope-strip-shaped vascular disruption. In our group of patients, one positive patient was under NBI mode in the microscopic examination for research, with the pathology of nasopharyngeal mucosal chronic inflammation, and NBI feature was that the mucosal vessels were in local circuitry.

Since the nasopharyngeal position is relatively deep, early-stage NPC symptoms were obvious. In particular, it can be easily missed and diagnosis could be delayed for subjects with no lymphatic metastasis. For positive patients with the EB virus antibody, once a lymphatic metastasis is found, the patients can be early diagnosed in a timely manner, in general. At the earlier stage, we have also come to a similar conclusion through tracking and following up other areas [26]. In our group data, eight I-period NPC cases were found under NBI mode, and only four I-period NPC cases were found under WL mode. Thong et al. [27] also considered that the NBI mode was beneficial to the early stage of the tumor, because tumors in the early stage may have no obvious neoplasm uplifting.

These present research results revealed that the sensitivity, specificity, and accuracy of the NBI mode are relatively higher than those of the WL mode for the diagnosis of NPC. Through the authenticity and reliability evaluation of these two modes, it was found that the NBI mode was superior to the WL mode. Therefore, we consider that endoscopic examination under the NBI mode should be applied to the diagnostic protocol of NPC, in order to significantly reduce the biopsy rate of non-NPC patients, relieve the subject’s pain, reduce the general investigation fund expenditure, and early detect NPC in patients.