Multi-Year Effect of Human Papillomavirus Vaccination on Recurrent Respiratory Papillomatosis.

OBJECTIVE: To examine whether human papilloma virus (HPV) vaccination in combination with surgical resection could suppress recurrence for an extended period of time in patients with recurrent respiratory papillomatosis (RRP). METHODS: In a prospective case series, data of patients who received combination therapy comprising surgery and quadrivalent HPV vaccination (Gardasil; Merck & Co., West Point, PA) were collected. Patients were followed up for RRP from March 2012 to July 2018 in an academic tertiary care center. The patients comprised 16 adults with RRP who were observed for >12 months after HPV vaccination, and whose HPV-DNA status was tested before and for >12 months after completion of combination therapy. The outcomes of this study were the severity score of larynx disease, tumor incidence rate, and relationship between this rate and HPV-DNA negative conversion after therapy. RESULTS: The severity score of laryngeal disease significantly decreased from before combination therapy to the time of final examination (P = 0.00045). The tumor incidence rate decreased to approximately 20% during the period from 12 to 47 months after HPV vaccination. Regarding HPV-DNA status in the final test results of each patient, 12 of 16 (75%) patients showed negative conversion; these 12 were significantly less likely to experience recurrence than patients who persistently tested positive for HPV-DNA during the period between 12 and 47 months after vaccination. CONCLUSION: HPV vaccination prevented recurrence associated with RRP surgery for 4 years in 80% of patients. This may be an effective adjuvant therapy, and HPV-DNA negative conversion after HPV vaccination might predict prevention of recurrence. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:442-447, 2020.

Efficacy of a silicone plug for patulous eustachian tube: A prospective, multicenter case series.

OBJECTIVES/HYPOTHESIS: To report the efficacy and safety of transtympanic plugging of the eustachian tube (ET) using a silicone plug (Kobayashi plug) for chronic patulous ET (PET). STUDY DESIGN: Prospective and multicenter trial conducted in which 30 PET patients were resistant to at least 6 months of conservative treatment. METHODS: The efficacy and safety of 28 and 27 patients, respectively, were analyzed. All patients fulfilled inclusion and exclusion criteria. The primary end point used the patulous eustachian tube handicap inventory-10 (PHI-10), and the secondary end point used ET function tests such as sonotubometry, tubo-tympano-aerodynamic-graphy, and respiratory movement of the tympanic membrane and auscultation of voice sounds transmitted from the nose through the ET to the external auditory canal at 3months after surgery. RESULTS: PHI-10 scores were 34.4 ± 4.2, 6.4 ± 9, and 5.7 ± 8.6 at screening, and 3 and 6 months after surgery. Twenty-three cases (82.1%, 95% confidence interval: 63.1%-93.9%) were judged as successes. There were five cases (17.2%) of middle ear effusion, four cases (13.8%) of tympanic membrane perforation, and one case of tinnitus due to surgery to remove the plug. No severe or life-threatening complications were found. CONCLUSIONS: This study revealed the efficacy and safety of silicone plug insertion for severe PET patients. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:1304-1309, 2020.

Effectiveness of chemoradiotherapy for radiation-induced bilateral external auditory canal cancer: A case report and literature review.

BACKGROUND: Radiation-induced bilateral external auditory canal cancer is an extremely rare disease that has yet to be fully characterized in the clinical literature. METHODS: Herein, we present a case study of a 75-year-old man with radiation-induced bilateral external auditory canal cancer. The patient's medical history included left maxillary cancer that had been treated with chemoradiation 19 years earlier and local recurrence with total maxillectomy 10 years earlier. Intracavitary radiation was delivered to the site of postoperative recurrence 8 years before the current presentation. The patient declined radical surgery for the external auditory canal cancer at this time, and a customized combined modality regimen was thus administered. RESULTS: There was no recurrence of cancer for 22 months, to date, after completing chemoradiotherapy. CONCLUSIONS: Our finding that radiotherapy can be successfully used for radiation-induced cancer indicates that chemoradiotherapy may be a useful strategy for treating this type of malignancy.

Development of a rat model of patulous eustachian tube by mandibular nerve resection.

OBJECTIVE: Patulous eustachian tube (PET) is currently treated using a variety of conservative or surgical approaches. To further elucidate the pathology of PET and to establish new therapies, the development of an animal model is necessary. The objective of this study was to develop a highly reproducible and sustainable rat model of PET by mandibular nerve resection. METHODS: Sixteen rats underwent mandibular nerve resection. Following an external incision, the main trunk of the mandibular nerve at the foramen ovale was identified in the pterygoid fossa, and its branches were resected. This surgery was performed on the right side, with the unoperated left side used as the control. To determine eustachian tube (ET) function, passive opening pressure (POP) was measured using inflation method up to Week 16 post-surgery. Changes in POP were statistically compared to the preoperative level on the operated and control sides. In addition, specimens of the ET and its surrounding tissue at Week 16 post-surgery were prepared for morphological evaluation in eight rats. RESULTS: On the control side, POP did not significantly decrease across the 16 weeks post-surgery compared to the preoperative level. In contrast, on the operated side, POP was significantly decreased at Week 2 and continued to be lower than the preoperative level until at least Week 16 post-surgery. POP dropped 10% or more on the operated side examined in thirteen rats. Histologically, the medial pterygoid muscle was atrophied on the operated side mainly. CONCLUSION: Mandibular nerve resection in rats may be an effective method for generating an animal model of PET. It was suggested that this rat model may be useful for verifying new treatments for PET.

Gardasil Vaccination for Recurrent Laryngeal Papillomatosis in Adult Men Second Report: Negative Conversion of HPV in Laryngeal Secretions.

BACKGROUND: In our first report on antibody levels in middle-aged and older men with recurrent laryngeal papillomatosis (RLP), we reported increases in human papillomavirus (HPV) antibody levels similar to those seen in adult women and young men. We posited that HPV antibodies produced in laryngeal mucus by Gardasil would prevent postoperative reinfection in patients with RLP. STUDY DESIGN: This is a case series study. PURPOSE: The purpose of this study was to examine whether Gardasil injection effectively inhibits recurrence of RLP. Specifically, in this second report, whether HPV antibodies produced in laryngeal secretions by Gardasil are capable of causing negative conversion of HPV-DNA (deoxyribonucleic acid) in laryngeal mucosa was investigated. METHODS: A total of 11 patients for whom antibodies were measured in the first report were studied. Before vaccination and after 1 year Post-vaccination, HPV screening tests were performed on laryngeal secretions, and whether HPV-DNA negative conversion had occurred was evaluated. At the time of collection of laryngeal secretions, the presence or absence of laryngeal papillomas was examined. RESULTS: Before vaccination, all patients were HPV low-risk positive on laryngeal secretion screening tests. After vaccination, three patients were positive. Laryngeal papillomas remained in five patients. CONCLUSIONS: The HPV-DNA test showed negative conversion in eight of 11 (72.7%) patients after vaccination. Residual laryngeal papillomas were found in five of 11 (45.5%) patients. The serum HPV antibody titer did not differ significantly between the group in which laryngeal secretions showed HPV negative conversion and the group in which conversion did not occur. The serum antibody titer did not differ significantly as a function of whether there were residual tumors.

Human Papillomavirus Infection Status of Various Laryngeal Diseases in Japan: A Comprehensive Study.

OBJECTIVE: The aim of our study was to clarify the human papillomavirus (HPV) infection status of various laryngeal diseases in Tokyo, Japan. STUDY DESIGN: This is a retrospective study. METHODS: A total of 144 patients who underwent surgical resection for various laryngeal lesions were enrolled in this study. These subjects were categorized into four groups based on lesion type: non-neoplastic, 44; precancerous, 29; cancer, 35; and papilloma, 36. To determine the rate of HPV infection, laryngeal secretions and resected tissue from our study participants were examined by liquid-phase hybridization (LPH) and consensus primer-directed polymerase chain reaction (PCR). RESULTS: The LPH for low-risk HPV was applied to all 144 patients, and that for high-risk HPV was additionally applied to 121 of the 144 patients. The PCR was applied to 94 of the 144 patients. The LPH detected low-risk HPV-DNA in 23 patients (1 cancer and 22 papillomas) and high-risk HPV-DNA in 3 patients (1 cancer and 2 papillomas). The PCR detected HPV-6 and HPV-11 in the papilloma group, whereas it detected HPV-31 in one patient with laryngeal cancer and one patient with precancerous lesion. Both the LPH and the PCR revealed the HPV infection rate in the non-neoplastic group to be 0%. CONCLUSIONS: Although we found no significant difference in the HPV-DNA positive rates of laryngeal cancer and precancerous lesions in the non-neoplastic group, the positive rates were significantly smaller in this group than in the papilloma group. In the Tokyo area, HPV had little or no association with laryngeal cancer, precancerous lesions, and non-neoplastic lesions in the larynx.

Gardasil Vaccination for Recurrent Laryngeal Papillomatosis in Adult Men: First Report: Changes in HPV Antibody Titer.

BACKGROUND: Patients with human papillomavirus (HPV) DNA-positive recurrent laryngeal papillomatosis commonly have repeated recurrences following surgery. The reason is suspected to be a mechanism by which latent HPV infection in the surrounding healthy mucosa reinfects the surgical site. It may be that production of HPV antibodies in the laryngeal mucosa with Gardasil injection could inhibit postoperative recurrence. STUDY DESIGN: This is a case series study. PURPOSE: The purpose of this study was to examine whether Gardasil injection effectively inhibits recurrence. However, as a first report, we describe the antibody titers before and after vaccination. METHODS: Gardasil was injected in 12 men (aged 32-74 years; mean age 47.9 years) with HPV-positive laryngeal papillomatosis. Serum antibody titers of HPV-6, -11, -16, and -18 were measured by a competitive Luminex-based immunoassay before the vaccination and 7 months after the start of the vaccination. RESULTS: Each of the antibody titers was very low before vaccination, and they rose in all patients after the vaccination. CONCLUSIONS: This finding demonstrates that antibody titers increase with Gardasil injection in post-adolescent males.

OK-432 injection therapy for cystadenocarcinoma of the parotid gland: A case report.

OK-432 is an immunomodulator that has been reported to be efficacious as an injection therapy for cervical lymphomas and ranulas. We performed OK-432 injection therapy to treat a cystadenocarcinoma of the parotid gland in a 72-year-old man. The 50 × 46-mm tumor was located in the deep lobe of the gland. The tumor had compressed the glossopharyngeal, vagus, and hypoglossal nerves, causing neurally mediated syncope, hoarseness, dysphagia, and dysarthria. A concentration of 5 KE/2 ml of OK-432 was injected. Within 2 months, the cyst had disappeared; no recurrence was apparent during 59 months of follow-up. To the best of our knowledge, no previous report has described injection of OK-432 for malignant cystic disease. We describe the injection method, injection dose, and postinjection course in the hope that this information will prove useful for future applications against malignant cystic disease.

Efficacy of a Single Dose of Basic Fibroblast Growth Factor: Clinical Observation for 1 Year.

OBJECTIVE: Basic fibroblast growth factor promotes wound healing by accelerating healthy granulation and epithelialization. However, the duration of the effects of a single intracordal injection of basic fibroblast growth factor has not been established, and administration intervals and timing have yet to be standardized. Here, we administered a single injection to patients with insufficient glottic closure and conducted follow-up examinations with high-speed digital imaging to determine the duration of the treatment response. STUDY DESIGN: Case series. METHODS: For treatment, 20 µg/mL recombinant human basic fibroblast growth factor was injected into two vocal cords. The following examinations were performed before the procedure and at 3-month intervals for 12 months starting at 1 month postinjection: Grade, Roughness, Breathiness, Asthenia, and Strain (GRBAS) scale assessment, maximum phonation time, acoustic analysis, high-speed digital imaging, glottal wave analysis, and kymographic analysis. RESULTS: Postinjection, the GRBAS scale score decreased, and the maximum phonation time was prolonged. In addition, the mean minimum glottal area and mean minimum glottal distance decreased. These changes were significant at 12 months postinjection compared with preinjection. However, there were no significant changes in the vibrations of the vocal cord margins. CONCLUSIONS: The intracordal injection of basic fibroblast growth factor improved insufficient glottic closure without reducing the vibrations of the vocal cord margins. This effect remained evident at 12 months postinjection. A single injection can be expected to yield a sufficient and persistent long-term effect.

Phonatory aerodynamics in connected speech.

OBJECTIVES/HYPOTHESIS: 1) Present phonatory aerodynamic data for healthy controls (HCs) in connected speech; 2) contrast these findings between HCs and patients with nontreated unilateral vocal fold paralysis (UVFP); 3) present pre- and post-vocal fold augmentation outcomes for patients with UVFP; 4) contrast data from patients with post-operative laryngeal augmentation to HCs. STUDY DESIGN: Retrospective, single-blinded. METHODS: For phase I, 20 HC participants were recruited. For phase II, 20 patients with UVFP were age- and gender-matched to the 20 HC participants used in phase I. For phase III, 20 patients with UVFP represented a pre- and posttreatment cohort. For phase IV, 20 of the HC participants from phase I and 20 of the postoperative UVFP patients from phase III were used for direct comparison. Aerodynamic measures captured from a sample of the Rainbow Passage included: number of breaths, mean phonatory airflow rate, total duration of passage, inspiratory airflow duration, and expiratory airflow duration. The VHI-10 was also obtained pre- and postoperative laryngeal augmentation. RESULTS: All phonatory aerodynamic measures were significantly increased in patients with preoperative UVFP than the HC group. Patients with laryngeal augmentation took significantly less breaths, had less mean phonatory airflow rate during voicing, and had shorter inspiratory airflow duration than the preoperative UVFP group. None of the postoperative measures returned to HC values. Significant improvement in the Voice Handicap Index-10 scores postlaryngeal augmentation was also found. CONCLUSIONS: Methodology described in this study improves upon existing aerodynamic voice assessment by capturing characteristics germane to UVFP patient complaints and measuring change before and after laryngeal augmentation in connected speech. LEVEL OF EVIDENCE: 4.

Assessment of human papilloma virus infection in adult laryngeal papilloma using a screening test.

OBJECTIVES: Human papilloma virus (HPV) infection is involved in both juvenile and adult laryngeal papilloma. We wished to determine which types of adult laryngeal papilloma were clinically related to HPV infection. We hypothesized that multiple-site and recurrent papillomas would have a strong relationship to HPV and conducted the present study to test this hypothesis. METHODS: Thirteen male patients with adult laryngeal papilloma who underwent resection of papilloma between August 2006 and September 2009 were studied. We examined the relationships between whether the tumor was solitary or multiple, presence or absence of recurrence after surgery, and HPV infection. High-risk HPV types (HPV-DNA types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) and low-risk HPV types (6, 11, 42, 43, and 44) were tested by a liquid-phase hybridization method. In addition, HPV typing was performed for patients positive for low-risk HPV types. Twenty patients with laryngeal carcinoma or laryngeal leukoplakia were enrolled as the control group. RESULTS: In the laryngeal papilloma group, all patients tested were negative for high-risk HPV and 69.2% were positive for low-risk HPV. Typing performed for seven of the patients who tested positive for low-risk HPV showed that one patient was positive for HPV-11, whereas the remaining six patients were positive for HPV-6. All patients with recurrent laryngeal papillomatosis (RLP) were positive for low-risk HPV. All patients who were positive for low-risk HPV had RLP. Tumor samples from repeat operations were positive for low-risk HPV in all patients tested. HPV was not detected in the control group. CONCLUSIONS: The relationship between RLP and low-risk HPV was strong, with all cases that were positive for low-risk HPV showing recurrence. Tumor tissue resected at the time of repeat surgery was positive for low-risk HPV in all cases tested.

Patients with phantogeusia show increased expression of T2R taste receptor genes in their tongues.

OBJECTIVES: The taste receptor gene family T2R has been implicated in the sensation of bitter taste. Phantogeusia is a spontaneous abnormal taste with no external stimulus. We analyzed the expression of T2R taste receptor genes in the tongues of patients with phantogeusia to assess their role in the pathogenesis of phantogeusia. METHODS: We obtained specimens from 43 patients with phantogeusia and 24 normal volunteers by scraping the foliate papillae and examined these specimens for the expression of 10 T2R taste receptor genes using reverse transcription-polymerase chain reaction and electrophoresis. RESULTS: The expression rate (subjects with detectable expression) of the 10 taste receptor genes in the healthy subjects ranged from 16.7% to 100%; 3 receptor genes were found in 50% or fewer of these subjects. In the patients with phantogeusia, the expression rate was increased significantly compared to that in the healthy control subjects for 3 of the 10 receptor genes examined. CONCLUSIONS: Our results show that the expression rate of some of the T2R taste receptor genes was increased significantly in patients with phantogeusia. These results suggest that increased expression of taste receptor genes is involved in the pathogenesis of phantogeusia; this finding may contribute to elucidation of the mechanism of this disorder.

Pharyngeal squamous cell papilloma in adult Japanese: comparison with laryngeal papilloma in clinical manifestations and HPV infection.

A number of reports have investigated the relationship between laryngeal papilloma and human papilloma virus (HPV) infection. On the other hand, it is unclear whether the HPV infection is involved in the occurrence of pharyngeal papilloma. We hypothesized that HPV infection was involved in the occurrence of pharyngeal papilloma similarly to laryngeal papilloma. To verify this hypothesis, we investigated the presence of HPV infection. Furthermore, clinical manifestations of pharyngeal papilloma, which had rarely been reported, were discussed. A male-to-female ratio, solitary or multiple occurrences, and koilocytosis were examined in cases with pharyngeal papilloma. HPV DNA was examined with unfixed surgically resected specimens of pharyngeal papilloma. A screening test by the liquid-phase hybridization method was carried out for the HPV high-risk group (16, 18, 31, 33, 35, 39, 45, 51, 56, 58, 59, and 68) and HPV low-risk group (6, 11, 42, 43, 44). As a control, 15 cases with laryngeal papilloma for which the same screening test was carried out were employed. Pharyngeal papilloma occurred as a solitary lesion more often, whereas laryngeal papilloma occurred as multiple tumors more frequently. The HPV infection rate was 0% in pharyngeal papilloma cases, which was in stark contrast with 66.7% in the HPV low-risk group in laryngeal papilloma cases. Pharyngeal papilloma occurred as a solitary lesion in females more frequently. Contrary to our hypothesis, the involvement of HPV infection was unlikely in the occurrence of pharyngeal papilloma.

Patients with hypogeusia show changes in expression of T2R taste receptor genes in their tongues.

OBJECTIVES/HYPOTHESIS: Taste receptor genes associated with bitterness belong to the T2R gene family. In this study, we compared the expression of genes of the T2R family in the tongues of patients with hypogeusia to those in healthy subjects and examined the possibility that T2R genes are involved in the pathogenesis of hypogeusia. STUDY DESIGN: Prospective clinical and basic study. METHODS: The control group consisted of 24 healthy people. The patient group consisted of 40 subjects with hypogeusia who were confirmed to have abnormally elevated taste thresholds including that of bitter taste. A tissue sample was collected from each individual by scraping the mucosa on the foliate papillae of the tongue. Total RNA was extracted from each sample and reverse transcribed. The expression of 10 T2R genes (TAS2R40, -R42, -R43, and -R48, and T2R3, -R8, -R9, -R10, -R13, and -R16) was evaluated by reverse transcriptase-polymerase chain reaction. RESULTS: Comparison of the frequency of gene expression between the control group and patients with hypogeusia showed that the frequency of expression of six receptor genes were significantly reduced in the hypogeusia patients. In particular, TAS2R40 showed a significant and marked decrease in the frequency of expression regardless of the cause or severity of hypogeusia. CONCLUSIONS: Our results suggest that decreased expression of taste-associated genes may be involved in hypogeusia in humans. In addition, the evaluation of taste receptor gene expression may be useful clinically for an objective diagnosis of hypogeusia or to evaluate the severity of the disorder.

Phonatory function of the elderly determined by intensity-loading test: a comparison with the young.

OBJECTIVE: The goal was to test the hypothesis that the elderly have diminished laryngeal regulation capability, so we investigated phonatory function in the elderly and young using a sound pressure-loading test. STUDY DESIGN AND SETTING: In 36 healthy men (17 in their 20s, 19 in their 70s) and 45 healthy women (22 in their 20s, 23 in their 70s), fundamental frequency, sound pressure level, mean flow rate (MFR), and expiratory lung pressure (EP) were determined from phonatory function testing. Subjects phonated at a comfortable level and at high intensity, without changing vocal pitch. RESULTS: MFR, EP, and airway resistance increased with high-intensity phonation in the young; however, only MFR and EP increased in the elderly. CONCLUSIONS: The findings supported our hypothesis: with high-intensity phonation, the elderly undergo unchanged laryngeal regulation but a greater degree of expiratory regulation. SIGNIFICANCE: The elderly are likely to become tired due to the effort required for phonation.

Facial nerve paralysis caused by middle ear cholesteatoma and effects of surgical intervention.

CONCLUSIONS: The clinical and surgical findings of this study indicated advanced cholesteatoma in many patients with facial paralysis. The outcome of facial paralysis was good. Poor outcomes were observed in cases with petrosal cholesteatoma and in those who underwent surgery > or = 2 months after the onset of paralysis. OBJECTIVE: To investigate clinical features of cholesteatoma associated with facial paralysis. MATERIAL AND METHODS: Sixteen patients with facial paralysis due to middle ear cholesteatoma were reviewed. After removal of the cholesteatoma lesion, a limited area of the fallopian canal, that in which facial nerve edema or redness was evident, was opened. Incision of the epineural sheath for nerve decompression was not performed. RESULTS: Initial paralysis was incomplete in 11 patients (69%). The onset of paralysis was sudden in 12 patients (75%). Labyrinthine fistulae (n = 9; 56%) and bone destruction in the cranial fossa (n = 10; 63%) were frequently observed. Six patients (38%) were totally deaf due to labyrinthitis. The outcome of facial paralysis was good in 13 patients (81%). Patients who underwent surgery > or = 2 months after the onset of paralysis frequently had a poor outcome. Paralysis was not improved in two cases with petrosal cholesteatoma.

Effect of myringotomy on prognosis in pediatric acute otitis media.

OBJECTIVE: In children with acute otitis media (AOM), we compared clinical outcomes between groups with and without myringotomy to elucidate the effect of this procedure on long-term clinical course and prognosis. METHODS: Fifty-nine children (29 male, 30 female) with tympanic membrane bulging or middle ear fluid (MEF) at initial presentation were assigned to one of two treatment groups. Group A received oral antibiotics and also underwent myringotomy at initial enrollment (36 cases), while group B received oral antibiotics without myringotomy (23 cases). Clinical outcomes were evaluated by otolaryngologic specialists using pneumatic otoscopy and tympanometry at 5, 10, 15, 30 days and 12 weeks and then every 2 weeks after the initial treatment. Otitis media with effusion (OME), early recurrence and recurrent AOM were used as the evaluation criteria for the prognosis. RESULTS: In group A, 6 children (16.7%) showed transition to OME, 11 (30.6%) showed early recurrence of AOM, and 9 (25.0%) developed recurrent AOM. In group B 10, 8, and 3 (43.5%, 34.8%, and 13.0%) showed these respective adverse outcomes. While early recurrence rates and recurrent AOM rates did not differ significantly between groups, progression of OME was significantly less frequent in group A than group B (P = 0.036). CONCLUSIONS: Lower rates of progression to OME in the group undergoing myringotomy suggested that myringotomy might be effective in preventing this outcome.