Human papilloma virus (HPV) types 6 and 11 are thought to infect the basal cells of the squamous epithelium. These infections cause laryngeal papillomatosis and condyloma acuminatum in the uterine cervix, which manifest the same pathological phenotype. The site of predilection is the junction of the stratified squamous epithelium and simple columnar epithelium (SCJ), however, the morphological characteristics of the epithelial junction in the larynx differ from that in the uterine cervix. Therefore, these observations suggest that the developmental mechanism of underlying the onset of laryngeal papilloma differs from that of condyloma acuminatum.
The newborn larynx, which is infected by HPV in case of juvenile-onset laryngeal papillomatosis, has no SCJ in the supraglottic regions. This suggests that HPV infects the laryngeal epithelium with or without SCJ. Moreover, the immaturity of the epithelia in the newborn larynx allows HPV to easily infect the tissue.
In investigations of adult larynges, the basal cells of the squamous epithelium and stratified ciliated epithelium in the larynx express p63, an epithelial stem cell marker. Integrin-α6 is, the receptor for HPV, is positive in the stratified ciliated epithelium and lower half of the squamous epithelium. These findings indicate that HPV is able to infect the squamous epithelium and stratified ciliated epithelium and that both infection with HPV in epithelial stem cells and stratification of epithelial cell layer are necessary for the development of laryngeal papilloma.

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Cidofovir is an anti-viral agent and has been anticipated to eradicate human papillomavirus in cases of recurrent respiratory papillomatosis (RRP). We herein summarize four new cases of more severe RRP than have been previously reported, which were treated with intralesional injection of the agent. Three of the four cases achieved minimal residual disease. However, recurrence of the disease was observed in all three cases, and further surgical intervention with intralesional injection of the agent was attempted. The remaining case had very severe disease requiring reduction of the tumor volume at the initial injection. Repeated recurrence required further surgical interventions with intralesional injection of the agent. The trends in Europe and the United States of America, as seen in statements approved by the RRP Task Force, should be considered when performing the treatment.

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Spasmodic dysphonia (SD) can be difficult to diagnose, and affected patients often see multiple physicians over many years before receiving a correct diagnosis.
In this study, questionnaires were sent to physicians who examined and treated patients with SD over a one-year period from 2012 to 2013. The questions included the number of SD patients seen within the past year, the characteristics of the disorder (medical history, symptoms and laryngeal findings) and the differential diagnosis. The questionnaires were sent to 91 university hospitals and voice clinics nationwide, of which 55 facilities (60.4%) responded.
The findings of the investigation are summarized below.
The total number of patients seen within the past one year was 894. Adductor SD was confirmed in 856 patients (95.7%), while abductor SD was detected in 37 patients (4.1%). The ratio of the adductor SD to abductor SD was consistent with that found in the literature. The results in this study revealed several common characteristic findings in the medical history, symptoms and laryngeal findings of the patients. In particular, the presence of hyperfunctional dysphonia, psychogenic dysphonia, and essential tremors should be used to distinguish SD. Assessing such characteristics may improve the ability to accurately diagnose SD. In addition, the use of screening questions, voice therapy, and lidocaine block were reported as differential diagnosis methods in this study.

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In this proceeding, we report the cases of 487 patients with spasmodic dysphonia (SD) who were injected with botulinum toxin (BT) into their laryngeal muscles (December 2006-January 2014 at Kumada Clinic). The sex ratio was 117:370 (M:F). The type ratio was 459:26:2 (adductor: abductor: “unusual”). This was based on our original classification of SD into three types, with the “unusual type” being defined as that which involves laryngeal muscles other than the TA or PCA, or involves more than two kinds of laryngeal muscles. Recently, we applied BT injections with a low dose-short interval (LDSI) (shorter than eight weeks) for SD patients who wanted to avoid the breathy hoarseness which is usually found for about two weeks after injections. Among 30 cases injected in January 2013, we applied LDSI for 10 cases throughout the following 12 months.

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Thyroarytenoid muscle myectomy (TAM) is a useful procedure for treating adductor spasmodic dysphonia (ADSD), in addition to type II thyroplasty (TP II), and both are performed in our department in Japan. In the present study, we examined the surgical outcomes of TAM.
The subjects were 31 patients who underwent TAM between 2008 and 2013 at Tokyo Medical University Hospital, who could be followed up for at least six months following surgery and whose voice quality evaluation data were available. A comparison of voice evaluations pre-surgery and six months post-surgery was made.
After six months, a significant improvement was seen in all of the voice quality evaluation items, including “strangulation”, “interruption”, “tremors” and voice handicap index (VHI). There was a marked recurrence of the symptoms in two of the 31 subjects within six months. Hemorrhage and scarring were observed as postoperative complications. In addition, we gave a questionnaire to 30 of the subjects who were followed up for at least one year following surgery, which asked about the recurrence of hoarseness and the degree of satisfaction with the surgery. Fifteen subjects responded (50%). The period of continuous hoarseness had ranged from one to 24 months. No subject felt that the hoarseness was a serious impediment in daily life, and the median period required for its disappearance was four months. Symptoms recurred in three subjects, but they tended to be mild. All 15 subjected reported experiencing a benefit from the surgery. The degree of satisfaction with TAM is very high, and we consider it to be a useful procedure for adductor spasmodic dysphonia.

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The purpose of this paper is to provide a concept, protocol and preliminary efficacy data for a behavioral voice therapy program for patients with adductor spasmodic dysphonia (ADSD). A voice therapy program was designed to target the underlying pathophysiology of focal laryngeal dystonia accompanying a disordered voice in patients with ADSD. The focus of the treatment was systematic voice training to improve the simple short nonspasmodic phonation to the conversational level. Twenty-one patients (twenty females, one male) were included in this therapy program. The outcome of the treatment was measured using the mora method. Recorded materials, including a passage from “The North Wind and the Sun” (24 morae total) read by the patients before and after the treatment were judged by three clinicians: two speech-language-hearing therapists and one otolaryngologist. The median score based on the mora method for all 21 patients was 24 pre-treatment and 12 post-treatment, indicating statistically significant improvement of the voice following treatment (Wilcoxon signed-ranks test, p<0.01). In detail, the score was improved in 10 patients, remained unchanged in 10 patients and was worsened in one patient after the treatment. Five (24%) of the twenty-one patients were satisfied with the effectiveness of the treatment, and required no further medical interventions. Our results indicated that behavioral voice therapy for ADSD was efficacious and could be a treatment option for ADSD.

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In this review, we describe how to diagnose and treat voice disorders from the viewpoint of their pathophysiology.
1) Phonation is a physical phenomenon wherein expiration vibrates the vocal fold to produces the voice. It is important to consider the vocal fold as a vibrating tissue when evaluating its pathophysiology. There are likely to be problems with vocal fold vibration in patients with voice disorders.
2) When you encounter voice disorder patients who lack findings associated with the vocal fold, it is necessary to check for the conditions necessary for normal vocal fold vibration (phonation).
3) You should consider the cause of difficulties in the vocal fold vibration as a vibrating tissue, and clarify the pathophysiology of the voice disorders from this point of view. In addition, multidisciplinary treatment (combined pharmacotherapy, surgical treatment and voice therapy) should be administered for voice disorders based on their pathophysiology.

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Functional dysphonia refers to dysphonia in a patient without any organic or neural disease. Psychogenic aphonia, phonasthenia, voice tremors, hyperfunctional dysphonia and mutational dysphonia are classified into the category of functional dysphonia. Conducting a medical interview is very important for obtaining a correct diagnosis, and it is necessary to consider the findings of fiberscopic images and voice and respiratory function tests from various viewpoints. The first choice of medical treatment is voice training, and close cooperation with a speech therapist is required.

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Among laryngeal cancers, which are often difficult to identify and diagnose, there is the possibility for cases of glottic cancer, similar to laryngeal polyps or cysts, and ventricular carcinoma of the larynx with swelling of the false fold. In the present case, we treated a patient with a lesion ventricular carcinoma, that was difficult to detect and diagnosed. The mass did not exhibit the characteristics of ventricular carcinoma to in the larynx and was instead located in the deep portion of the laryngeal ventricle; therefore, its discovery was delayed . In addition, only swelling of the false fold was observed under an endoscope and the lesion may progress, requiring laryngectomy, during follow up. Ventricular carcinomas often progress in the top and bottom of the glottis region within the paraglottic space, making it difficult to detect such tumors early. In addition, ventricular carcinomas easily develop lymph node and distant metastaseis.
We herein report the cases of the patient with false fold swelling who were found to have ventricular carcinoma of the larynx, and discuss the clinical and pathological characteristics of the tumor.

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Myxoma is a benign mesenchymal tumor and occurs rarely in the head and neck region. We report a case of a myxoma of the larynx in a 36-year-old woman. Her symptoms are gradually progressive hoarseness and difficulty of phonation. Endoscopic examination revealed a solid mass in the subglottic area of the anterior commissure.
Phonosurgery performed with a microscope showed that the mass was encapsulated and located in the subglottic mucosa. This hard, elastic mass which measured 10 mm in diameter, was diagnosed as a myxoma. Although excision was microscopically incomplete, there is no evidence of recurrence macroscopically 13 months after the surgery and she remains asymptomatic.

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A thyroid-cartilage foraminal cyst is uncommon among the rare congenital laryngeal cysts, and common manifests stridor and dyspnea. We present a patient with a thyroid-cartilage foraminal cyst resected according to the extra-laryngeal approach, and discuss the literature.
A 7-day-old infant boy with severe stridor was referred to the pediatrics department. On admission, respiratory care via directional positive airway pressure was commenced; however, the stridor worsened. He was then referred to our department for assessment of his upper respiratory tract. Flexible fiberoptic laryngoscopy revealed a submucosal swelling of the left laryngeal ventricle to the arytenoid and a stenosis in the glottis gap. Based on computed tomography findings of a cystic lesion, a congenital larynx cyst was suspected. Cyanosis occurred at 21 days of age, and endoscopic fenestration was undertaken twice, but was ineffective. We performed the extra-laryngeal resection method and laryngofissure approach, and excised the cyst. After the last operation, the stridor improved, but a slight hoarseness remained. There has been no recurrence for 18 months following surgery.
In this case, cyst resection by the extra-laryngeal approach was useful when the endoscopic transoral approach was ineffective. Physicians should consider resection according to the extra-laryngeal approach in patients with suspected congenital larynx cyst in which the endolaryngeal approach is unsuccessful.

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Differential diagnosis of patients who present with vocal cord paralysis can be difficult. We describe a patient who presented with vocal cord paralysis, which lead to a diagnosis of mediastinal lung cancer.
The patient, a forty-seven-year-old female, complained of laryngeal pain and hoarseness. A detailed examination revealed paralysis of the right vocal cord, but did not uncover weight loss, pharyngeal and laryngeal tumors, and cervical lymphadenopathy. Plain computed tomography (CT) showed small thyroid nodules and small lymphadenitis in the subclavicular fossa and mediastinum, but was otherwise indefinite. Positron emission tomography (PET) CT undertaken a month after the initial presentation showed a rapid increase in the size of the esophageal and mediastinal nodules, multiple lymph nodes and distant metastases. Gastrointestinal fiberscopy did not reveal esophageal cancer. Based on PET-CT, GIF and neck nodule fine needle aspiration findings, she was diagnosed with mediastinal lung cancer. Chemotherapy was commenced, and the clinical course was good.
Mediastinal symptoms including vocal cord paralysis and superior vena cava syndrome can be primary symptoms of mediastinal lung cancer. Otolaryngologists should consider mediastinal lung cancer in the differential diagnosis of patients presenting with mediastinal symptoms.

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Amyloidosis accounts for less than 1% of all benign tumors of the larynx. We herein report a case of supraglottic amyloidosis in the larynx.
A37-year-old male presented with a three-year history of hoarseness of voice. The initial examination revealed a tumor with a smooth surface on the left false vocal cord, with intact vocal cord mobility. We subsequently performed laryngomicrosurgery and resected the tumor. Histopathologically, the specimen showed submucosal deposition of amyloid with hematoxylin and Congo red staining. A diagnosis of systemic amyloidosis was excluded on follow-up examinations. The patient’s voice quality improved, and with no episodes of recurrence for five years after the surgery.
Amyloidosis of the larynx is a rare and usually benign condition. However, long-term follow-up is required in such cases, as the disease may recur a long time after treatment.

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