The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing, especially in developed countries, among individuals aged ≤60 years (1). Human papillomavirus is a risk factor for OPSCC; the increase in the prevalence of human papillomavirus infection over the last few decades has attributed to the significant increase in OPSCC incidence (2-4). Advances in transoral surgery and the emergence of transoral robotic surgery (TORS) have resulted in a paradigm shift in treatment strategies for OPSCC (5,6). Transoral surgery is a minimally invasive treatment option for OPSCC; however, accurate and early preoperative endoscopic diagnosis is crucial for enabling radical resection of the lesions through this approach. Traditionally, transoral examination of the oropharynx is performed macroscopically using a head mirror, headlight, and tongue depressor; this method remains widely used at present. Recent advances in optical instruments have enabled detailed observation of the structure of the pharynx and mucosal surfaces using electronic endoscopes, enabling early-stage head-and-neck cancer detection, including that of the oropharynx (7). There have been very few reports on the endoscopic examination of the oropharynx; a gastrointestinal endoscope has been used in all previous studies (8,9). Moreover, there have been no endoscopic studies in the field of otorhinolaryngology. We anticipate that accurate endoscopic diagnosis in the field of otorhinolaryngology will contribute to the detection of early-stage OPSCC.

We performed transoral endoscopy of the oropharynx in healthy participants using a flexible endoscope, which is appropriate for otorhinolaryngology, tongue protrusion, and phonation procedures, without a tongue depressor, to examine the diagnostic performance of the tongue protrusion with phonation and open mouth (TOPPOM) method for visualizing structures of the oropharynx.

Study design. Twenty healthy participants between the ages of 20 and 75 years were enrolled for the present study. The exclusion criteria were as follows: head-and-neck diseases, including those of the oral cavity and oropharynx, underlying systemic diseases, pregnancy, and breastfeeding. All clinical investigations were conducted according to the principles of the Declaration of Helsinki. The study and all its protocols were approved by the Tokyo Medical University Ethics Committee (Registration number: SH3690). All participants understood the purpose of the study and provided written informed consent before any of the procedures were carried out.

Endoscopy procedure. An Olympus ENF-VH videoscope (Olympus Medical Systems, Tokyo, Japan) was used for otorhinolaryngology, and the images were recorded on an Olympus VISERA ELITE video system (Olympus Medical Systems). Endoscopy was performed with the participants seated with their head placed in a fixed position (Figure 1). The examiner inserted the endoscope transorally without using a tongue depressor. The oropharynx was then observed in the following three conditions: 1) with the participant opening the mouth only (open mouth; OM), 2) with phonation and open mouth (POM), and 3) with TOPPOM. Participants were instructed to open their mouth as wide as possible; subsequently, some were instructed to phonate a long ‘e’ (as in egg) and some were instructed to protrude their tongue. During the individual procedures, 12 oropharyngeal subsites (Figure 2A-L) and the proximity of the mucosa to each of the 12 subsites (Figure 3A-H) were observed. The subsites were as follows: the soft palate, left and right anterior palatine arches, left and right palatine tonsils, left and right posterior palatine arches, posterior oropharyngeal wall, left and right lingual tonsillar sulcus, tongue base, and vallecula.

Evaluation. Scores were assigned as follows at all 12 subsites of the oropharynx under each of the three conditions: 2 points when the entire subsite was clearly observed, 1 point when only partial observation was possible, and 0 points when the subsite was not observed at all. The proximity images of the mucosa for each subsite were also recorded and scored in the same way, i.e., 2 points were awarded if the dendritic vasculature in the background of the mucosa could be clearly observed, 1 point if it could not be clearly observed, and 0 points if it could not be observed at all. The numbers of these regions were the same as the number of subsites. The primary endpoint was the total score (out of 48), representing the view of all subsites and proximity images of the mucosa. The rate of the endpoint was compared between the three conditions through superiority comparison. The secondary endpoint was the total score (out of 4) relating to the complete view of individual oropharynx subsites and proximity images. The rate of the secondary endpoint was compared among the three conditions. One otorhinolaryngologist acted as the examiner and three other otorhinolaryngologists evaluated the endoscopic images.

Statistical analysis. Continuous data are presented as the mean±standard deviation. The scores were compared between the OM, POM, and TOPPOM conditions using the Kruskal–Wallis and Dann-Bonferroni tests. A p-value <0.05 was considered a statistically significant difference. All statistical analyses were performed using SPSS version 24.0 (IBM Corp., Armonk, NY, USA).

The mean total score for all oropharynx subsites during OM, POM, and TOPPOM were 15±4.86, 27±4.86, and 34±4.19 points, respectively. The differences in the mean scores between OM and POM, OM and TOPPOM, and POM and TOPPOM were statistically significant (p<0.001 for all) (Figure 4, Table I). Evaluation of the scores of individual subsites revealed that in six of the subsites – the left and right anterior palatine arches, left and right palatine tonsils, left lingual tonsillar sulcus, and vallecula – the scores were significantly higher for TOPPOM than for POM and significantly higher for POM than for OM. However, the scores for the soft palate, left and right posterior palatine arches, right lingual tonsillar sulcus, posterior wall, and tongue base were significantly higher during POM and TOPPOM than during OM, and there was no significant difference between the scores for POM and TOPPOM (Figure 5, Table I).

Our study demonstrates that TOPPOM allows significantly better endoscopic observation than POM or OM alone. Furthermore, observation of the anterior palatine arches, palatine tonsils, lingual tonsillar sulcus, and vallecula was significantly improved during TOPPOM compared to that during POM or OM only, whereas all subsites of the oropharynx were more easily observed during POM than during OM only. This could be attributed to the phonation of a long ‘e’ that raises the soft palate and widens the pharyngeal cavity. In addition, tongue protrusion causes the lower edges of the anterior palatine arches to be pulled anteriorly by the tongue. This extends the pharyngeal cavity forward, allowing the lower edges of the anterior palatine arches and palatine tonsils, which are hidden by the tongue during POM, to be clearly observed. The mean scores of the lingual tonsillar sulcus, tongue base, and vallecula were good and were the highest in TOPPOM, followed by POM, and the lowest in OM. There was a significant difference between the scores in TOPPOM and POM for the left lingual tonsillar sulcus and vallecula only. The lingual tonsillar sulcus, tongue base, and vallecula are deep within the oropharynx; therefore, they were difficult to observe in some cases because of the gag reflex, which may have affected the results. Observation of the soft palate, anterior palatine arches, palatine tonsils, posterior palatine arches, and posterior wall by transnasal endoscopy, which is commonly used by otorhinolaryngologists, is likely to be insufficient because these subsites are generally tangential to a nasal endoscope and are difficult to observe. Images of the posterior wall are particularly difficult to obtain because this region is tangential to the transnasal endoscope. Transoral endoscopy provides an effective alternative because the soft palate, anterior and posterior palatine arches, palatine tonsils, and posterior wall are perpendicular to the endoscope, enabling easy observation.

The traditional macroscopic method of surgery involves a head mirror, headlight, and tongue depressor and enables observation in one direction only since the equipment remains outside of the oral cavity. The angle of insertion of the endoscope can be optimized to observe the mucosal surfaces from various angles, enabling detection of superficial cancers and lesions in the palatine tonsil crypts. In addition, because the endoscope can reach deep inside the oral cavity, a tongue depressor is not necessary to achieve a good field of view. However, the observation of deep subsites of the oropharynx such as the lingual tonsillar sulcus, tongue base, and vallecula is considered to be poor, as indicated by the low mean score even during TOPPOM. Since these parts are well observed using conventional transnasal endoscopy, the transnasal endoscopy and the TOPPOM method should be used together in routine medical practice.

According to the concept of field cancerization, head-and-neck squamous cell carcinoma and esophageal squamous cell carcinoma frequently exist synchronously or metachronously (10), and a strong connection between excessive drinking and smoking and multicentric carcinogenesis has been demonstrated (11). Such cases require comprehensive examination of the head-and-neck region including the oropharynx and esophagus.

Diagnosis of superficial head-and-neck carcinoma, including of the oropharynx, can be achieved using digestive endoscopes (7,12). In otorhinolaryngology, however, macroscopic observation is routinely conducted using a head mirror and headlight (13,14). Furthermore, the endoscopes used in otorhinolaryngology are small, meaning that only charge-coupled devices (CCDs) with small diameters can be attached, resulting in inferior images compared to those obtained with large-diameter digestive endoscopes attached to high-resolution CCDs; moreover, image enhancement was not introduced until recently. Collectively, these factors hindered the detection of superficial carcinoma. In recent years, the potential image quality of otorhinolaryngology endoscopes has improved with the advent of narrow band imaging, in which vascular information is emphasized and expressed. Therefore, it has become possible to diagnose minute lesions that are difficult to recognize by white light observation by visualizing characteristic vascular abnormalities in tumor tissue (15), permitting the detection of superficial carcinomas during screening of high-risk patients--such as those with esophageal carcinomas--for head-and-neck carcinoma (16). Early detection means that minimally invasive treatment including transoral resection is possible, which helps to maintain organ function and quality of life (17). We consider that the use of the TOPPOM method can further increase the rate of early detection of oropharyngeal carcinoma by enabling comprehensive examination of the oropharynx.

New techniques have been developed for examining the hypopharynx, such as the modified Killian method (18), and clear observation of this region as far as the esophageal orifice is now possible. We think that detailed examination of the head-and-neck region using the modified Killian method in conjunction with transnasal endoscopy should be combined with the TOPPOM method to include observation of the oral cavity. This will not only improve the results when screening this region but will also contribute to improving medical care for malignancies through facilitating pre-treatment diagnosis, preoperative determination of resection scope and evaluation of treatment outcomes for oropharyngeal lesions as well as other inflammatory and benign diseases. Recently, good outcomes have been reported in oropharyngeal carcinoma following TORS (19), and we believe that accurate diagnosis of the extent of cancerous lesions by endoscopy using the TOPPOM method will greatly contribute to complete resection with TORS and other transoral resective procedures.

This study has some limitations that should be acknowledged. First, we included only healthy participants; thus, no lesions of the oropharynx were examined. Evaluation of lesions in routine clinical practice using our suggested method should be conducted. Second, we did not compare our results with macroscopic observations. However, the comparison would be difficult since the evaluation of macroscopic observations is subjective, and the evaluation of endoscopic images is objective (as in the present study).

The TOPPOM method can improve the results of transoral endoscopy of the oropharynx and enable comprehensive examination with conventional transnasal endoscopy of the head-and-neck region. The literature on transoral endoscopic examination of the oropharynx is scarce, and the TOPPOM method may contribute to the discovery of the cause of early oropharyngeal cancer and cancer of unknown primary origin in addition to reducing oversight. Moreover, early detection enables prompt treatment and allows for the selection of a less invasive treatment. Future studies should investigate whether the ability to diagnose early oropharyngeal cancer could be improved by using this method.

The Authors declare that they have no competing interests in relation to this study.

RT was responsible for data collection and analysis, drafting and editing the manuscript. HS was responsible for idea development, study design, data analysis, drafting and editing the manuscript. IO and AS were responsible for data analysis. KT was responsible for idea development and study design. All Authors read and approved the final manuscript.