Early enteral nutrition and mobilization following head and neck surgery with free flap reconstruction.

BACKGROUND: Perioperative management methods that reduce surgery-associated invasiveness and improve the quality of postoperative recovery are being promoted as enhanced recovery after surgery programs in various areas. Early enteral nutrition and mobilization are essential elements for enhanced recovery after surgery; however, their safety and feasibility are unclear in head and neck surgery with free tissue transfer reconstruction. This study aimed to clarify these uncertainties. METHODS: This is a retrospective before-after study. From 2018 to 2022, 187 and 173 patients received conventional management on or before April 2020 and early management on or after May 2020, respectively. The conventional management and early management groups received enteral nutrition and mobilization on postoperative days 2 and 1, respectively. The primary outcome for safety assessment was the incidence of complications. The secondary outcome was the compliance rate of conventional management or early management for feasibility assessment and the length of hospital stay. RESULTS: The clinical tumour-node-metastasis stage and American Society of Anesthesiologists physical status showed significant differences between the groups. In multivariable analysis, the early management group demonstrated a significantly lower incidence of treatment-required complication classified Clavien-Dindo Grade 2 and above (odds ratio = 0.57; 95% confidence interval = 0.31-0.92) and lower wound infection (odds ratio = 0.53; 95% confidence interval = 0.31-0.92). The early management group had lower compliance rate than the conventional management group; however, no statistically significant difference was observed (79.8% vs. 85.0%, P = 0.21). CONCLUSION: Early management is safe and feasible following head and neck surgery with free tissue transfer reconstruction. It could reduce the complication rate and is considered a useful postoperative management method.

Extracting interpretable features for pathologists using weakly supervised learning to predict p16 expression in oropharyngeal cancer.

One drawback of existing artificial intelligence (AI)-based histopathological prediction models is the lack of interpretability. The objective of this study is to extract p16-positive oropharyngeal squamous cell carcinoma (OPSCC) features in a form that can be interpreted by pathologists using AI model. We constructed a model for predicting p16 expression using a dataset of whole-slide images from 114 OPSCC biopsy cases. We used the clustering-constrained attention-based multiple-instance learning (CLAM) model, a weakly supervised learning approach. To improve performance, we incorporated tumor annotation into the model (Annot-CLAM) and achieved the mean area under the receiver operating characteristic curve of 0.905. Utilizing the image patches on which the model focused, we examined the features of model interest via histopathologic morphological analysis and cycle-consistent adversarial network (CycleGAN) image translation. The histopathologic morphological analysis evaluated the histopathological characteristics of image patches, revealing significant differences in the numbers of nuclei, the perimeters of the nuclei, and the intercellular bridges between p16-negative and p16-positive image patches. By using the CycleGAN-converted images, we confirmed that the sizes and densities of nuclei are significantly converted. This novel approach improves interpretability in histopathological morphology-based AI models and contributes to the advancement of clinically valuable histopathological morphological features.

Dose-Finding and Efficacy Confirmation Trial of the Superselective Intra-arterial Infusion of Cisplatin and Concomitant Radiation Therapy for Locally Advanced Maxillary Sinus Cancer (JCOG1212): Results of the Efficacy Confirmation Phase in Patients with T4aN0M0.

PURPOSE: Locally advanced maxillary sinus cancers require radical surgery as a standard treatment, but this often results in significant disfigurement and impairment of function. JCOG1212 seeks to evaluate the safety and efficacy of the superselective intra-arterial infusion of cisplatin and concomitant radiation therapy (RADPLAT) for T4aN0M0 and T4bN0M0 maxillary sinus squamous cell carcinomas. We herein report the results of the efficacy confirmation phase in the T4a cohort. METHODS AND MATERIALS: Patients received 100 mg/m2 cisplatin intra-arterially weekly for 7 weeks with concomitant radiation therapy (total 70 Gy) as determined by the results of the preceding dose-finding phase. The trial aimed to evaluate the primary endpoint of 3-year overall survival (OS), comparing RADPLAT with the historical control for 3-year OS in surgery (80%). RESULTS: From April 2014 to August 2018, 65 patients were registered in the T4a cohort from 18 institutions, consisting of 54 men and 11 women with a median age of 64 years (range, 40-78 years) and Eastern Cooperative Oncology Group performance status 0/1 (58/7). After excluding 1 ineligible patient, 64 patients were included in the primary analysis of efficacy and safety. The median follow-up was 4.5 years in all eligible patients, and the primary endpoint for 3-year OS was 82.8% (90% CI, 73.4%-89.2%). With regard to acute adverse events, mucositis (grade ≥3), neutropenia (grade ≥3), increased creatinine (grade ≥2), hearing impairment (grade ≥2), and stroke (grade ≥2) were observed in 20.3%, 14.1%, 3.1%, 3.1%, and 1.6% of patients, respectively. One treatment-related death due to a thromboembolic event was reported. CONCLUSIONS: We demonstrated that RADPLAT showed favorable results for patients with T4aN0M0 maxillary sinus squamous cell carcinomas compared with the historical control for 3-year OS in surgery, which was from an earlier period, and showed some specific toxicities. Therefore, RADPLAT, as well as surgery, can be regarded as a possible treatment option for these patients.

Second free jejunum transfer after flap loss does not affect oral intake: A retrospective case-control study.

PURPOSE: Free jejunum transfer is one of the standard procedures for restoring oral intake after total pharyngo-laryngo-esophagectomy. Flap loss leading to a second free jejunum transfer rarely occurs. This study investigated the impact of a second free jejunum transfer on post-operative oral intake. METHODS: A retrospective review was conducted on patients who underwent a first free jejunum transfer between July 1998 and December 2019. A total of 367 patients were included in the study. Among them, 17 patients who underwent a second free jejunum transfer because necrosis constituted the second free jejunum transfer group, whereas 350 patients who did not require a second free jejunum transfer formed the first free jejunum transfer group. The incidence of dysphagia requiring tube feeding and post-operative complications was compared between the two groups. Moreover, risk factors for dysphagia and complications were estimated. RESULTS: There were no statistically significant differences in the incidence of dysphagia post-operation between the two groups. A second free jejunum transfer was a statistically significant factor for complications at 2- and 6-months post-operation; however, there were no significant differences in complication rates at the 12-month follow-up. Furthermore, there were no significant differences in the incidence of severe complications between the two groups. CONCLUSION: Although a second free jejunum transfer increases early complications, it is not associated with major complications and does not negatively impact oral intake. These findings support the conclusion that free jejunum transfer is safe and helps maintain post-operative quality of life.

Long-term outcomes of patients with oral cavity cancer receiving postoperative radiotherapy after salvage neck dissection for cervical lymph node recurrence.

BACKGROUNDS: We aimed to clarify the outcomes of postoperative radiotherapy (PORT) after salvage neck dissection for cervical lymph node (LN) recurrence in oral cavity cancer. METHODS: We retrospectively evaluated overall survival (OS), recurrence-free survival (RFS), recurrence patterns, and adverse events of 51 patients with high-risk features receiving PORT after salvage neck dissection between 2009 and 2019. RESULTS: After a median follow-up of 7.4 years from PORT initiation, the 7-year OS and RFS rates were 66.3% (95% CI: 54.0-81.3) and 54.6% (95% CI: 42.1-70.9), respectively. Age <70 years and isolated LN recurrence were significantly associated with longer OS and RFS. Among the 22 patients who experienced recurrence, 14 experienced recurrence within the radiation field. PORT-related grade 3 acute mucositis (35%) and late adverse events (osteoradionecrosis [4%] and laryngeal stenosis [2%]) were observed. CONCLUSIONS: PORT after salvage neck dissection for cervical LN recurrence achieved good survival with acceptable toxicity.

Nasopharyngeal Carcinoma Treated With Photoimmunotherapy.

Photoimmunotherapy is a new treatment modality in which a tumor-targeting monoclonal antibody is combined with a photoactivated dye and a laser is applied to destroy tumor cells. In Japan, insurance reimbursement for this treatment started in January 2021 for unresectable locally advanced or locally recurrent head and neck cancer. We used photoimmunotherapy to treat two patients with recurrent nasopharyngeal squamous cell carcinoma (NPSCC). The first patient was diagnosed with NPSCC (T1N0M0) and treated with definitive radiotherapy, leading complete response. A local recurrence was observed and treated with photoimmunotherapy. Seven months have passed, complete response is archived. The second patient was diagnosed with NPSCC (cT2N1M1). Multimodal therapy led to a complete response for all lesions. A local recurrent lesion appeared, and photoimmunotherapy has been repeatedly performed. The lesion was controlled as a stable disease for about one year. Photoimmunotherapy could be an effective treatment for local recurrence of NPSCC after radiotherapy.

Priority of the basic and instrumental activities of daily living in older patients with cancer prescribed rehabilitation: a cross-sectional survey.

BACKGROUND: There is no information on whether vulnerable older patients with cancer consider basic activities of daily living (BADL) and instrumental activities of daily living (IADL) important outcomes. Our survey aimed to investigate the priority of BADL and IADL in outcomes among vulnerable older patients with cancer. METHODS: This was a single-center survey in a Japanese cancer center. Eligible patients were ≥ 65 years of age and were prescribed in-hospital rehabilitation while under cancer treatment. Using original self-administered ranking questionnaires, patients were asked to rank outcomes and subdomain of BADL and IADL. High-priority domains were defined as the highest, second-highest, and third-highest priority domains in individuals. RESULTS: A total of 169 patients were analyzed. The mean age was 74.0 years (standard deviation, 5.1 years) and the number of males was 107 (63%). The order of ranking of high-priority outcomes was BADL and IADL (n = 155), cognitive function (n = 91), mental function (n = 82), nutrition (n = 61), social function (n = 51), comorbidity (n = 39), and life span (n = 28). The top three high-priority independence subdomains of BADL and IADL were toilet use (n = 140), feeding (n = 134), and mobility (n = 69) among the BADL and shopping (n = 93), food preparation (n = 88), and ability to handle finances (n = 85) among the IADL. CONCLUSIONS: BADL and IADL can be considered the most important health outcomes in clinical trials and in practice among older patients with cancer and physical vulnerabilities.

Eligibility for Photoimmunotherapy in Patients with Unresectable Advanced or Recurrent Head and Neck Cancer and Changes before and after Systemic Therapy.

Photoimmunotherapy is a novel cancer treatment that recently became covered by national health insurance in Japan, but treatment decision-making remains challenging for unresectable advanced or recurrent head and neck cancer. We aimed to clarify the characteristics of patients for whom photoimmunotherapy was indicated by a retrospective chart review. Patients aged ≥20 years diagnosed with advanced or recurrent head and neck cancer who started receiving systemic therapy at the National Cancer Center Hospital East from January 2016 through December 2020 were retrospectively analyzed. Before and after first-line systemic therapy, patients were classified into 3 groups according to eligibility for photoimmunotherapy: eligible, potentially eligible, and ineligible. In total, of 246 patients evaluated-194 after exclusions were analyzed-108 were deemed ineligible for treatment. Of the remaining 86 patients, 8 were considered potentially eligible and 9 eligible. Of the nine eligible patients, four became ineligible after receiving first-line systemic therapy due to disease progression. Our results suggest that the indication of photoimmunotherapy should be considered before, during, and after systemic therapy for unresectable locally advanced or recurrent head and neck cancer.

Potential efficacy of local therapy for progressive lesions after nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: In recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), local therapy (LT) such as surgery or radiotherapy can be treatment options for improved survival or quality of life. To date, however, few reports have addressed the efficacy of LT for sites of disease progression after immune checkpoint inhibitors, including other cancers. METHODS: We conducted a retrospective analysis of patients with R/M SCCHN originating from the oral cavity, oropharynx, hypopharynx, and larynx and treated with nivolumab. We extracted patients undergoing salvage LT or palliative radiotherapy (RT) to the selected progressive lesion at any time after initiation of nivolumab. RESULTS: Twenty-four patients received LT. Salvage LT was performed in 9 (37.5%) patients, including surgery and definitive RT in 5 and 4 patients, respectively. Palliative RT was performed in 15 (62.5%) patients. LT was provided in 10 (41.7%) patients for oligoprogressive disease. Twelve (50.0%) patients received subsequent systemic therapy immediately after LT. Classification based on patient treatment divided the population into four subgroups with different prognoses (salvage LT followed by subsequent systemic therapy [n = 3], salvage LT alone [n = 6], palliative RT followed by subsequent systemic therapy [n = 9], and palliative RT alone [n = 6]). Median OS in this order was 24.5, 9.0, 7.3, and 2.4 months (p = 0.001). All patients in the salvage LT followed by subsequent systemic therapy group continued nivolumab. CONCLUSION: In R/M SCCHN patients who have received nivolumab, salvage LT for the selected progressive lesion with continuation of nivolumab potentially provides an excellent survival prognosis.

Clinical outcome of endoscopic-assisted transoral surgery for superficial cancer of pharyngo-esophageal junction.

BACKGROUND: Endoscopic-assisted transoral surgery (TOS) for superficial cancer of the pharyngo-esophageal junction (PEJ) is risk of stricture, and therapeutic outcomes are unclear. This study aimed to evaluate clinical outcomes of endoscopic-assisted TOS for superficial PEJ cancers. METHODS: We retrospectively compared clinical outcomes of endoscopic-assisted TOS for superficial PEJ cancers (group A) and of other sites in the hypopharynx (group B). RESULTS: The group A comprised 12 lesions in 12 patients, and group B comprised 198 lesions in 146 patients. Group A and group B exhibited en bloc resection rates of 100% and 99%. Median operative times were 82 and 37 min (p < 0.001). The frequency of stricture and local recurrence in group A was significantly higher in group B (42% vs. 1%, p < 0.001; 25% vs. 6%, p = 0.036). All adverse events could be managed with conservative treatments. CONCLUSIONS: Endoscopic-assisted TOS is not ideal for treating superficial PEJ cancers compared to other sites.

Factors affecting polyglycolic acid sheet engraftment success for covering mucosal defects from head and neck surgery.

BACKGROUND: Polyglycolic acid (PGA) sheets have been used with fibrin glue to cover extensive mucosal defects in oral and pharyngeal surgery; however, the sheets can fall off before wound healing is completed. Hence, prolonged fasting is often recommended in such patients. However, there are few studies on the factors that shape PGA sheet engraftment. We studied sheet engraftment rates considering these factors. METHODS: All consecutive cases of oral surgery in 2013-21 in which the defect was covered with fibrin glue and Neoveil® or Neoveil Nano® PGA sheets were identified. The loss of all sheets was defined as an engraftment failure. Multiple logistic regression analysis was conducted to identify whether the PGA-sheet type, application site, defect size and postoperative fasting duration predicted engraftment. RESULTS: Overall, 137 patients were identified (mean age, 73 years; 57% male). The surgeries were conducted with Neoveil® in 66% of the patients; the most common site was the buccal mucosa (25%), and the mean defect size and fasting duration were 709 mm2 and 4 days, respectively. The engraftment rate was 76%. Neoveil Nano® PGA sheets were associated with a 2.8-fold better engraftment rate than Neoveil® (univariate: 87 vs. 70%, P = 0.032; multivariate: 95% confidence intervals = 1.067-7.410, P = 0.036). Other variables, including fasting duration, were not predictive of engraftment. CONCLUSIONS: This is the largest case series of patients with head and neck cancer who underwent fibrin glue-PGA sheet defect coverage. The fasting duration did not influence engraftment. Therefore, early oral intake is not contraindicated in such patients.

Anatomical classification of pharyngeal and laryngeal endoscopic images using artificial intelligence.

BACKGROUND: The entire pharynx should be observed endoscopically to avoid missing pharyngeal lesions. An artificial intelligence (AI) model recognizing anatomical locations can help identify blind spots. We developed and evaluated an AI model classifying pharyngeal and laryngeal endoscopic locations. METHODS: The AI model was trained using 5382 endoscopic images, categorized into 15 anatomical locations, and evaluated using an independent dataset of 1110 images. The main outcomes were model accuracy, precision, recall, and F1-score. Moreover, we investigated focused regions in the input images contributing to the model predictions using gradient-weighted class activation mapping (Grad-CAM) and Guided Grad-CAM. RESULTS: Our AI model correctly classified pharyngeal and laryngeal images into 15 anatomical locations, with an accuracy of 93.3%. The weighted averages of precision, recall, and F1-score were 0.934, 0.933, and 0.933, respectively. CONCLUSION: Our AI model has an excellent performance determining pharyngeal and laryngeal anatomical locations, helping endoscopists notify of blind spots.

A Case Series on Pain Accompanying Photoimmunotherapy for Head and Neck Cancer.

One of the most severe side effects of photoimmunotherapy (PIT) for head and neck cancer is pain. As there are presently no detailed reports on pain and pain management in PIT, we conducted a retrospective case series study. We conducted a retrospective study of five patients who had received PIT at the National Cancer Center Hospital East between January 2021 and June 2022 using medical chart data. All patients experienced pain, evidenced by an increased numerical rating scale (NRS) after PIT, regardless of the illumination method. The daily change in mean NRS rating shows that the pain was highest on the day of PIT, with ratings of 6.8 and 7.8 for the frontal and cylindrical diffuser methods, respectively; it dropped the following day quickly. Four of the five patients received fentanyl injections for postoperative pain management beginning on postoperative day (POD) 0. All patients who underwent therapy using a cylindrical diffuser required postoperative pain management with opioid drugs. Pain after PIT tended to be most intense immediately after or one hour after illumination and declined the following day, suggesting the need to have a pain relief plan in place in advance.

Post-operative progress of arm abduction function and rate of lymph node metastasis around the region of the accessory nerve: a multicentre prospective observational study.

OBJECTIVE: Although neck dissection is an essential technique in the surgical treatment of head and neck carcinoma, arm abduction disorders occurring after neck dissection reduce the patient's quality of life. METHODS: We prospectively evaluated the rate of lymph node metastasis in Levels IIB and V in head and neck cancer patients who underwent neck dissection at eight centres in Japan. In addition, post-operative arm abduction disability was classified according to functional assessment values at 1 month post-operatively, and the rate of maintained function at 6 and 12 months was evaluated. RESULTS: Lymph node metastasis occurred in Level IIB in 12 of 242 cases (4.9%) and in Level V in 5 cases (2.1%) during the 12-month post-operative course. In patients with preservation of the ipsilateral accessory nerve, arm abduction function was maintained in 142 of 209 patients (67.9%) at 12 months after surgery. Post-operative radiotherapy and Level V dissection had no statistically significant effect on the recovery of arm abduction function. Level V dissection caused a temporary loss of abduction function post-operatively. A higher arm abduction test score at 1 month post-operatively was associated with a higher rate of subsequent ability to maintain arm abduction function. CONCLUSIONS: In patients classified as cN0, metastatic rate at Levels IIB and V was low. In this cohort, omitting Level V dissection may be an option in strategies aimed at maintaining arm abduction function.

Human papillomavirus-related multiphenotypic sinonasal carcinoma.

Human papillomavirus-related multiphenotypic sinonasal carcinoma (HMSC) is a rare primary tumor of the sinonasal tract that has been reported recently. It is reportedly associated with human papillomavirus infection. The tumor presents with glandular cyst-like histology, but some cases exhibit squamous epithelialization and are positive on p16 immunohistochemical staining. The clinical picture and treatment of this disease have not been established. However, this report describes a recurrent case of this disease treated with salvage surgery. The patient was a 61-year-old woman who presented to the previous doctor with a chief complaint of nasal obstruction. A localized tumor was found in the left nasal cavity and was resected under endoscopic guidance. The postoperative pathological diagnosis was HMSC. Twenty-one months after the surgery, local recurrence was observed, and the patient was referred to our hospital. Since the recurrent lesion had widely infiltrated outside the nasal cavity, extensive resection and reconstructive surgery were performed. Postoperative radiotherapy was performed as an additional treatment. Notably, 13 months have passed since the salvage surgery, and no recurrence has been observed to date.

Immunohistochemical Analysis of Common Cancer Antigens in Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: The prognosis of recurring and metastatic head and neck squamous cell carcinoma (HNSCC) is poor. Although immune checkpoint inhibitors have expanded the treatment options for HNSCC, the response rates are low. Alternatively, cancer vaccines and T-cell therapies are being developed. Identification of useful common cancer antigens and confirmation of human leukocyte antigen (HLA) class I expression are required. MATERIALS AND METHODS: Immunohistochemistry analyses were performed for 10 antigens (FOXM1, TGFBI, SPARC, HSP105α, WT1, AFP, GPC3, PP-RP, KIF20A, KM-HN-1) and HLA class I using specimens of 56 surgical cases. Staining intensity, percentage of stain-positive areas, and localization of staining in the tumor cells and normal tissue were evaluated. RESULTS: Staining of FOXM1, TGFBI, SPARC, and HSP105α was more predominant in tumor cells than that in normal cells. The expression rates of these antigens in tumor cells were 60.7%, 58.9%, 73.2%, and 50.0%, respectively. Regarding sites, the expression rates of these antigens in oral cancer were high at 57.1%, 71.4%, 81.0%, and 66.7%, respectively. Furthermore, the expression of HLA class I was 83.9% in all cases. Of these, 68.1% showed expression on the plasma membrane. CONCLUSION: FOXM1, TGFBI, SPARC, and HSP105α could be useful common cancer antigens, and HLA class I is expressed on the plasma membrane of cancer cells in many cases. The results suggest that cancer vaccines and T-cell therapy may be clinically viable options for HNSCC treatment.

Clinical assessment of early mobilization after head and neck free flap reconstruction: A retrospective case-control study.

PURPOSE: We examined whether there were any differences in perioperative complications between patients who mobilized on the first postoperative day (early mobilization) and those who mobilized on the second postoperative day after head and neck reconstruction using free tissue transfer. METHODS: In the control group (n = 74), patients were instructed to mobilize on the second postoperative day (April 2019-March 2020), while in the early mobilization group (n = 101), patients were instructed to mobilize on the first postoperative day (April 2020-March 2021). Mobilization was defined as maintaining a standing position or walking. Clinical data were collected from medical records and retrospectively analyzed. RESULTS: There were no significant differences in clinical background factors, with the exception of intraoperative blood loss volume. The proportion of patients who successfully mobilized on the day of instruction was significantly lower in the early mobilization group (89.1% vs. 98.7%). One case of total flap loss and four cases of partial flap loss occurred in the control group, and three cases of partial flap loss occurred in the early mobilization group. There was no significant difference in partial or total flap loss between the two groups. There were no significant differences in other perioperative complications (wound infection, postoperative bleeding, and delirium) between the two groups. The median postoperative hospital stay was 24.5 and 25.0 days in the control and early mobilization groups, respectively. CONCLUSION: In this study, early mobilization on the first day after head and neck free flap reconstruction was safe and feasible.

Comparison between three age-stratified cohorts reveals poor prognosis of young patients with tongue carcinoma.

Objectives: Investigation of the prognosis of young patients with tongue carcinoma has been the focus of several recent studies aimed at improving future precision treatment. Most studies have been two-cohort investigations comparing young and older patients, who have wide discrepancies in prognosis. Older patients, especially those aged >70 years, often have a poor general condition. This affects the prognosis of the older cohort and accounts for the discrepancies observed in two-cohort studies. Accordingly, in this study, older patients (aged ≥71 years) were separated and compared to young and middle-aged patients. Methods: A total of 257 patients with oral tongue carcinoma referred during 2011-2017 were analyzed. Patients were sorted into young (aged ≤40 years), middle-aged (aged ≥41 and ≤70 years), and older (aged ≥71 years) groups. Overall survival (OS) and disease-free survival (DFS) were compared among the groups. Furthermore, patterns of recurrence rates were compared. Results: Compared with young patients, there was no difference in OS or DFS for older patients (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.5-2.7 and HR: 0.7, 95% CI: 0.4-1.2, respectively) in a multivariate analysis. There was also no difference in OS (HR: 0.6, 95% CI: 0.3-1.3) for middle-aged patients. However, middle-aged patients had low recurrence rates (HR: 0.5, 95% CI: 0.3-0.8). With respect to the recurrence type, middle-aged patients had a low local recurrence rate (HR: 0.3, 95% CI: 0.1-0.7). Conclusion: Three-cohort studies should be conducted to evaluate whether the prognosis of young patients with tongue carcinoma is truly poor in terms of future precision treatment.

The characteristics of missed pharyngeal and laryngeal cancers at gastrointestinal endoscopy.

OBJECTIVES: Understanding the miss rate and characteristics of missed pharyngeal and laryngeal cancers during upper gastrointestinal endoscopy may aid in reducing the endoscopic miss rate of this cancer type. However, little is known regarding the miss rate and characteristics of such cancers. Therefore, the aim of this study was to investigate the upper gastrointestinal endoscopic miss rate of oro-hypopharyngeal and laryngeal cancers, the characteristics of the missed cancers, and risk factors associated with the missed cancers. METHODS: Patients who underwent upper gastrointestinal endoscopy and were pathologically diagnosed with oro-hypopharyngeal and laryngeal squamous cell carcinoma from January 2019 to November 2020 at our institution were retrospectively evaluated. Missed cancers were defined as those diagnosed within 15 months after a negative upper gastrointestinal endoscopy. RESULTS: A total of 240 lesions were finally included. Eighty-five lesions were classified as missed cancers, and 155 lesions as non-missed cancers. The upper gastrointestinal endoscopic miss rate for oro-hypopharyngeal and laryngeal cancers was 35.4%. Multivariate analysis revealed that a tumor size of <13 mm (odds ratio: 1.96, P=0.026), tumors located on the anterior surface of the epiglottis/valleculae (odds ratio: 2.98, P=0.045) and inside of the pyriform sinus (odds ratio: 2.28, P=0.046) were associated with missed cancers. CONCLUSIONS: This study revealed a high miss rate of oro-hypopharyngeal and laryngeal cancers during endoscopic observations. High-quality upper gastrointestinal endoscopic observation and awareness of missed cancer may help reduce this rate.

Human papillomavirus-related oropharyngeal carcinoma.

It was not until around 2000 that human papillomavirus-related oropharyngeal carcinoma was recognized as carcinoma with clinical presentations different from nonrelated head and neck carcinoma. Twenty years after and with the revision of the tumor-node-metastasis classification in 2017, various clinical trials focused on human papillomavirus-related oropharyngeal carcinoma to improve the prognosis and quality of life of patients with this disease. However, the incidence of human papillomavirus-related cancers is increasing, which is expected to be particularly prominent in Japan, where human papillomavirus vaccination is not widely available. In this review, we describe the current status of clinical trials (mainly focused on initial surgery and radiation dose reduction) for, primary and secondary prevention of, and the present status of human papillomavirus-related oropharyngeal carcinoma in Japan.