Laryngeal disorders in people living with HIV.

OBJECTIVES: Several studies have shown that HIV infected individuals are at higher risk compared to the general population of developing non-AIDS defining conditions such as some types of cancer, kidney disease, liver disease and others. In this case-control study, we compared the incidence of laryngeal disorders between a treatment-seeking HIV-positive population and uninfected controls. We aimed to investigate whether there are any laryngeal disorders that are overrepresented in HIV-positive individuals. METHODS: This was a case-control study based on retrospective chart review, comparing the incidence of laryngeal, airway, and swallowing disorders in sixty-nine HIV positive individuals and 4178 HIV negative controls treated between January 1, 2016 and December 31, 2017, at the Johns Hopkins Voice Center. RESULTS: A majority of HIV-infected patients (59.4%) had at least one diagnosis belonging to the Vocal cord pathology category compared to 48.2% of controls (OR 1.57, p = 0.065). Compared to the entire treatment-seeking population, HIV patients were more likely to present with laryngeal cancer (15.9% vs. 3.4% in controls, OR 5.43, p < 0.001) and chronic laryngitis (17.4% vs. 4.2%, OR 4.79, p < 0.001). Fungal and ulcerative laryngitis were also overrepresented in HIV-positive individuals (OR 9.45, p < 0.001 and 6.29, p < 0.001, respectively). None of the diagnoses categorized as functional voice disorders, swallowing, or airway problems showed a significant difference between groups. Laryngeal papillomatosis, which is an HPV-dependent disease, had similar prevalence in both groups. CONCLUSIONS: Treatment-seeking HIV-positive patients presenting to a laryngology clinic suffer significantly more often from laryngeal squamous cell carcinoma as well as chronic, fungal, and ulcerative laryngitis compared to HIV-negative individuals. LEVEL OF EVIDENCE: 4.

Cytomegalovirus-associated supraglottic mass in a patient on immunosuppressive therapy.

A 33-year-old woman on chronic immunosuppressive treatment for rheumatoid arthritis with a history of inhaled methamphetamine use presented with respiratory failure requiring mechanical ventilation for a prolonged period. After being given plasma exchange, pulses of methylprednisolone and a dose of cyclosporine for suspected ANCA (anti-neutrophilic cytoplasmic autoantibodies) vasculitis, she developed an obstructive supraglottic laryngeal mass that required a tracheostomy to bypass. Biopsy findings revealed the mass to be an inflammatory pseudomass secondary to cytomegalovirus (CMV). The mass resolved after several weeks of intravenous ganciclovir therapy. This is an extremely unusual presentation of localised CMV disease, with only two or three similar cases having been reported worldwide.

Initial Experience Treating HPV-Related Laryngeal Diseases with Oral Brincidofovir: A Pilot Study.

OBJECTIVE: To determine if brincidofovir, an oral analog of cidofovir that achieves high tissue levels of the active metabolite with low systemic toxicity, has an observable effect on HPV-related disease of the larynx. METHODS: Two patients with laryngeal recurrent respiratory papillomatosis (one each of genotypes 6 and 11) and 1 with recurring aryepiglottic fold carcinoma in situ (genotype 16) received oral brincidofovir according to protocol. Close-range videoendoscopic examinations were done during and after the study period to observe disease behavior in the absence of other interventions, and after subsequent surgical intervention. Disease character and magnitude of recurrence for each patient were compared to their patterns prior to brincidofovir. RESULTS: Brincidofovir reduced papilloma burden in 1 patient and markedly attenuated the rate and magnitude of recurrence in both. After surgical intervention, Patient 1 remains disease-free at 10 years (7 years from last intervention) and Patient 2 has no symptoms at 8 years. Patient 3 with recurring carcinoma in situ has required less frequent resections and specimens show reduced degrees of dysplasia present only in islands amid normal mucosa at 8 years (currently no evidence of disease at 21 months from last intervention). CONCLUSION: Brincidofovir appears to attenuate HPV disease of the larynx in this small pilot study, though further investigation is required because of the highly variable nature of the disease and potential confounding factors.

Factors Related to Extralaryngeal Spread in Juvenile Recurrent Respiratory Papillomatosis.

OBJECTIVES/HYPOTHESIS: To identify factors associated to increased risk of extra-laryngeal spread in pediatric patients with recurrent respiratory papillomatosis (RRP). STUDY DESIGN: Retrospective chart review. METHODS: A retrospective study was conducted evaluating the clinical charts of patients younger than 16 years with histopathologically confirmed RRP treated between January 2014 and December 2018. Characteristics of patients with and without extra-laryngeal disease dissemination were compared. Odds ratios were calculated and multivariate logistic regression analysis was performed. RESULTS: Data from 82 patients were analyzed. Mean age at symptom onset was 42 months. Fifteen (18.29%) patients had extra-laryngeal spread (ELS) at time of diagnosis and in four, the disease continued to spread to other sites. Of 67 patients with disease restricted to the larynx, 17 (25.37%) developed ELS during the disease course. Human papilloma virus (HPV) typing was performed in 49 (59.8%) patients; in 28 (57.1%) HPV subtype 6 was identified and in 21 (42.9%) HPV subtype 11. ELS was found in 11 patients with serotype 11 (52.38%) and in seven patients with serotype 6 (25%) (P = .048). Statistically significant differences for ELS were also found for age at diagnosis younger than 5 years (P = .045), presence of tracheostomy (P = .031), and need for adjuvant therapy (P = .010). CONCLUSIONS: Age at diagnosis of RRP younger than 5 years and presence of tracheostomy were factors related to ELS. A statistically significant association between infection with HPV subtype 11 and ELS were also observed. Adjuvant medication might be considered a protective factor against ELS. Laryngoscope, 131:1652-1656, 2021.

Laser Plume From Human Papillomavirus-Infected Tissue: A Systematic Review.

BACKGROUND: Laser procedures are becoming more prevalent across multiple medical specialties for a variety of indications. The plumes created by these lasers have raised concern for the dissemination of an infectious material. OBJECTIVE: To review and summarize the information on viral dissemination in laser plumes available in the literature. MATERIALS AND METHODS: Data Sources A systematic review was performed on English and non-English articles using the PubMed and the Cochrane databases. A manual search of bibliographies from relevant articles was also performed to collect additional studies. STUDY SELECTION: Only articles in the English language with full texts available that pertained to viral particles in laser plumes were included. Data Extraction Two authors performed independent article selections using predefined inclusion and exclusion criteria. RESULTS: There have been case reports of possible transmission of human papillomavirus (HPV) by inhalation of laser-produced aerosols. Multiple investigators have attempted to recreate this scenario in the laboratory to qualify this risk. Others have conducted clinical experiments to determine the presence of HPV in laser plumes. CONCLUSION: The current body of the literature suggests that laser surgeons are at a risk for HPV exposure by inhalation of laser-derived aerosols. We offer best practice recommendations for laser operators.

Vocal cord surgery and pharmacological treatment of a patient with HPV and recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is caused by persistent infection of the respiratory epithelium by human papillomavirus (HPV), especially HPV 6 and 11. We present a case of surgically treated RRP. The main purpose of our protocol is to remove the lesions with a non-aggressive surgical technique and prevent recurrences with the use of cidofovir for local infiltrations in multiple sessions. We use low-power energy CO2 laser, directed towards the upper part of the vocal cord, to determine a retraction of the mucosa with consequent coverage of the epithelium of the free edge. The aim of this technique is to treat and stop the formation of synechia of the anterior commissure and the free margin of the vocal cords in the anterior commissure. After 8 years follow-up, there are no signs of recurrence of the disease. The voice had a net improvement confirming the effectiveness of the protocol.

Prevalence and clinical implications of low-risk human papillomavirus among patients with recurrent respiratory papillomatosis in Rio de Janeiro, Brazil.

OBJECTIVE: The aim of this study was to investigate the presence of human papillomavirus (HPV) in biopsy specimens from juvenile and adult patients with histopathological diagnosis of recurrent respiratory papillomatosis (RRP) treated in two public hospitals in Rio de Janeiro, Brazil. METHODS: We performed the detection and genotyping of HPV by PCR technique for the types 6, 11, 16, and 18 in biopsy specimens from 41 RRP patients. RESULTS: The juvenile onset RRP (JoRRP) corresponded to 61% and the adult onset RRP (AoRRP) corresponded to 39% of the study group. Prevalence of males was observed in both the adult (81.3%) and the juvenile (56%) groups. Lesions in the larynx were more frequent in the glottis (46%). Genotyping analysis only revealed patients with HPV-6 (34.1%), HPV-11(17.1%), and co-infection HPV-6 and -11 (48.8%). RRP severity was significantly associated with the JoRRP (p<0.001), with extralaryngeal disease and more surgeries. However, no significant association between RRP severity and HPV types was found. One co-infected patient in the JoRRP died due to the evolution of the disease with lung involvement. CONCLUSION: These results show the strong association of HPV-6 and/or HPV-11 types with RRP and could complement the diagnosis, prognosis, and therapies for these patients. In addition, the HPV vaccination should be encouraged to prevent the disease.

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.

Human papillomavirus infection in the oromaxillofacial area: Clinical anatomy and histological considerations.

Clinical manifestations of human papillomavirus (HPV) infection in the head and neck can range from benign lesions, which are the most frequent, to malignant lesions. The prevalence of head and neck cancer is increasing, despite currently decreasing trends in known risk factors such as smoking and alcohol use. A new patient profile has appeared in recent practice: most frequently a middle-aged male patient who does not smoke or drink alcohol, is sexually active (possibly having multiple partners), and presents with oral or cervicofacial lesions requiring diagnosis and treatment. Another risk factor that should be considered in these patients is HPV infection. The association of oral potentially malignant disorders (OPMD) with HPV is a challenge for the medical practitioner. The gold standard for diagnosis is histopathological examination, which can also yield evidence suggesting HPV infection. Determination of the viral genotype provides additional data for assessing the oncological risk of an HPV infection. Treatment of these patients is aimed at removing the lesions, in association or not with antiviral treatment and recurrence control.

Immunological responses against human papilloma virus and human papilloma virus induced laryngeal cancer.

OBJECTIVE: This study aimed to clarify the local immune status in the larynx in the presence of infection or carcinogenesis associated with human papilloma virus. METHODS: Cytological samples (for human papilloma virus detection) and laryngeal secretions (for immunoglobulin assessment) were obtained from 31 patients with laryngeal disease, during microscopic laryngeal surgery. On histological examination, 12 patients had squamous cell carcinoma, four had laryngeal papilloma and 15 had other benign laryngeal disease. Cytological samples were tested for human papilloma virus DNA using the Hybrid Capture 2 assay. RESULTS: High risk human papilloma virus DNA was detected in 25 per cent of patients (three of 12) with laryngeal cancer. Low risk human papilloma virus DNA was detected only in three laryngeal papilloma patients. The mean laryngeal secretion concentrations of immunoglobulins M, G and A and secretory immunoglobulin A in human papilloma virus DNA positive patients were more than twice those in human papilloma virus DNA negative patients. A statistically significant difference was observed between the secretory immunoglobulin A concentrations in the two groups. Patients with laryngeal cancer had higher laryngeal secretion concentrations of each immunoglobulin type, compared with patients with benign laryngeal disease. The study assessed the mean laryngeal secretion concentrations of each immunoglobulin type in the 12 laryngeal cancer patients, comparing human papilloma virus DNA positive patients (n = 3) and human papilloma virus DNA negative patients (n = 9); the mean concentrations of immunoglobulins M, G and A and secretory immunoglobulin A tended to be greater in human papilloma virus DNA positive cancer patients, compared with human papilloma virus DNA negative cancer patients. CONCLUSION: These results suggest that the local laryngeal immune response is activated by infection or carcinogenesis due to human papilloma virus. The findings strongly suggest that secretory IgA has inhibitory activity against infection or carcinogenesis associated with human papilloma virus in the larynx.

Does HPV have a presence in diffuse high grade pre-malignant lesions of the larynx?

OBJECTIVE: To describe the incidence of HPV in diffuse high grade pre-cancerous lesions of the larynx. METHODS: Patient charts were searched for those who presented between October 2008 and June 2009 with diffuse vocal fold leukoplakia. Biopsy proven laryngeal lesions with high grade dysplasia or carcinoma-in-situ (CIS) were examined for patient characteristics and presence of high-risk type HPV detected by in situ hybridization technique. RESULTS: Fifteen patients with precancerous lesions were identified. Average age was 63 years and 13 were male. One lesion was identified as positive for high-risk HPV, all other lesions were negative. At current follow up, no patient has demonstrated progression to invasive carcinoma. CONCLUSION: HPV may not play a role in non-progressing diffuse high-grade lesions of the larynx.

Detection of human papillomavirus and adenovirus in benign and malignant lesions of the larynx.

OBJECTIVE: To investigate the role of human papillomavirus (HPV) and adenovirus (AdV) infections in the oncogenesis of squamous cell carcinomas of the larynx and of laryngeal dysplasia. STUDY DESIGN: Cross-sectional study with planned data collection. SETTING: Department of Otorhinolaryngology G. Ferreri and Department of Experimental Medicine and Pathology-Section of Virology, Sapienza University of Rome. SUBJECTS AND METHODS: Biopsy samples were taken from 68 patients with benign and malignant lesions of the larynx. All tissue samples were analyzed by means of polymerase chain reaction with two groups of primers for HPV and with a pair of primers for AdV. RESULTS: All cases of carcinomas and dysplasia as well as all control cases were negative for both viruses. Four of the five cases of laryngeal papillomas were positive for only HPV, confirming the role of these viral types in the origin of papillomas. CONCLUSION: The absence of viral genomes in laryngeal carcinomas as in the other cases studied suggests the existence of other factors that play a more important role than viral infection in the carcinogenesis of these lesions.

Laryngeal zoster with multiple cranial nerve palsies.

A young immunocompetent patient is presented with a very rare presentation of a common viral illness: herpes zoster of the left hemilarynx with sensorial and motoric neuropathy of three ipsilateral lower cranial nerves: IX, X and XI. The mucosal lesions were discovered during upper gastrointestinal endoscopy. PCR of erosional exsudate confirmed the clinical diagnosis. Antiviral therapy and corticosteroids possibly contributed to the prosperous evolution with complete healing.

The supplementary diagnostic power of selected immunohistochemical, molecular genetic and infective parameters in epithelial hyperplastic laryngeal lesions.

OBJECTIVES: MIB-1 and p53 protein expression, loss of heterozygosity (LOH), microsatellite instability (MSI) of di- and mononucleotide repeats, and HPV status were tested for their potential to characterize different stages of epithelial hyperplastic laryngeal lesions (EHLL). METHODS: Thirty-two EHLL were reclassified according to the Ljubljana classification into simple (SH), abnormal (AbH), atypical hyperplasia (AtH) and carcinoma in situ, and investigated by immunohistochemical methods, PCR and direct sequencing analysis. RESULTS: MIB-1 increased with progressive grades of EHLL, whereas p53 protein expression was distinctive only between SH and AbH. LOH showed increasing frequency with grades of the lesions, but the distribution of altered loci (9p, 9q, 10q, 11q, 17p) was not qualified to differentiate between the stages. MSI was detected in SH, AbH and AtH without clear correlation to histopathological grading. HPV infection occurred mostly in SH and AbH (both: 66.7%). CONCLUSION: MIB-1 labeling and allelic loss could assist histopathological diagnosis in the entire spectrum of EHLL, whereas the MSI results point to a genetic instability of the laryngeal mucosa in general and are therefore not helpful in the distinction of different stages of EHLL. However, future molecular genetic analyses should consider more late events of laryngeal carcinogenesis to improve their diagnostic potential. Furthermore, our results indicate that nonrisky and risky EHLL could probably be caused by different exogenous factors.

[Herpesviridae and laryngeal neoplasia].

OBJECTIVE: To investigate the relationship between herpesviridae and malignant or benign laryngeal diseases. METHOD: 128 paraffin-embedded laryngeal squamous cell carcinoma and laryngeal epithelium hyperplastic lesions were detected by polymerase chain reaction (PCR) and PCR-ISH for herpesviridae. RESULT: HSV-1 was detected in 10 cases by PCR, among them 3 were laryngeal squamous cell carcinoma (LSCC), 1 was carcinoma in situ(CIS), 4 were laryngeal polyps and 2 were laryngeal keratosis. Except 1 LSCC and 1 CIS 8 of 10 cases were positive while detected by PCR-ISH. In benign diseases, signals were shown from basal layer to superficial cell; in malignant lesions, the signals were scattered in the diseases. CONCLUSION: Most of laryngeal diseases were not related to herpesviridae, but HSV-1 may acts as initiator in the development of a few cases.

Juvenile onset recurrent respiratory papillomatosis: possibilities for successful antiviral therapy.

Recurrent respiratory papillomatosis (RRP) is a potentially devastating disease that can have significant morbidity, and can even result in mortality due to airway compromise or, less commonly, malignant transformation. Two distinct types of RRP exist: adult-onset RRP (AO-RRP) and juvenile-onset RRP (JO-RRP). Acquisition of human papillomavirus (HPV), the causative agent of RRP, is believed to occur in the peripartum period in the case of JO-RRP, with disease symptoms (primarily hoarseness) becoming apparent during the first several years of life. Treatment currently consists of surgical debulking of the papillomas to relieve airway obstruction. However, numerous antiviral therapies have also been evaluated, albeit primarily under uncontrolled settings. This article will review the biology, natural history and management of HPV infection, with particular emphasis on JO-RRP.

[Laryngeal herpes. A case report]. / Herpes laríngeo. A propósito de un caso.

An interesting case of laryngeal herpetic involvement simulating a neoplasm in its gross appearance and the production of paralysis is reported. The patient was diagnosed as thymoma three months later. The possibilities of differential diagnosis and relation with immunosuppression states are discussed.