Laryngotracheal aspiration test reduce the false negative rate in patients with suspected SARS-COV-2 pneumonia despite a negative nasopharyngeal swab.

BACKGROUND: In the emergency department (ED) definitive diagnosis of SARS-COV-2 pneumonia is challenging as nasopharyngeal swab (NPS) can give false negative results. Strategies to reduce false negative rate of NPS have limitations. Serial NPSs (24-48 h from one another) are time-consuming, sputum can not be collected in the majority of patients, and bronchoalveolar lavage (BAL), the most sensitive test, requires specific expertise. Laryngotracheal aspiration (LTA) is easy to perform and showed a similar accuracy to BAL for diagnosis of other pulmonary diseases, however it was not studied to diagnose SARS-COV-2 pneumonia. OBJECTIVE: An observational cross-sectional study was performed to evaluate the negative predictive value of LTA in patients with suspected SARS-COV-2 pneumonia despite a negative NPS. METHODS: In the EDs of two university hospitals, consecutive patients with suspected SARS-COV-2 pneumonia despite a negative NPS underwent LTA performed with a nasotracheal tube connected to a vacuum system. Final diagnosis based on all respiratory specimen tests (NPS, LTA and BAL) and hospital data was established by two reviewers and in case of discordance by a third reviewer. RESULTS: 117 patients were enrolled. LTA was feasible in all patients and no patients experienced adverse events. Fifteen (12.7%) patients were diagnosed with community-acquired SARS-COV-2 pneumonia: 13 LTA positive and only 2 (1.7%) LTA negative. The negative predictive value of NPS and LTA was 87.3% (79.9% - 92.7%) and 98.1% (93.3%99.8%) respectively. CONCLUSIONS: LTA resulted feasible, safe and reduced false negative rate in patients with suspected SARS-COV-2 pneumonia despite a negative NPS.

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.

Novel biomarkers for the prediction of COVID-19 progression a retrospective, multi-center cohort study.

A pandemic designated as Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Up to date, there is no efficient biomarker for the timely prediction of the disease progression in patients. To analyze the inflammatory profiles of COVID-19 patients and demonstrate their implications for the illness progression of COVID-19. Retrospective analysis of 3,265 confirmed COVID-19 cases hospitalized between 10 January 2020, and 26 March 2020 in three medical centers in Wuhan, China. Patients were diagnosed as COVID-19 and hospitalized in Leishenshan Hospital, Zhongnan Hospital of Wuhan University and The Seventh Hospital of Wuhan, China. Univariable and multivariable logistic regression models were used to determine the possible risk factors for disease progression. Moreover, cutoff values, the sensitivity and specificity of inflammatory parameters for disease progression were determined by MedCalc Version 19.2.0. Age (95%CI, 1.017 to 1.048; P < 0.001), serum amyloid A protein (SAA) (95%CI, 1.216 to 1.396; P < 0.001) and erythrocyte sedimentation rate (ESR) (95%CI, 1.006 to 1.045; P < 0.001) were likely the risk factors for the disease progression. The Area under the curve (AUC) of SAA for the progression of COVID-19 was 0.923, with the best predictive cutoff value of SAA of 12.4 mg/L, with a sensitivity of 83.9% and a specificity of 97.67%. SAA-containing parameters are novel promising ones for predicting disease progression in COVID-19.

HPV infection and clinical profiles in laryngeal diseases. A preliminary study.

PURPOSE: The study analysed the presence of HPV in samples tissue from laryngeal chronic hyperplastic inflammation, with and without pre-neoplastic potential, and from squamous cell carcinoma of the larynx. The aim of this analysis was to evaluate the presence/absence of different types of HPV and their relationship to the clinical profile of the patients studied (habit of smoking and drinking). METHODS: Sixty cases were randomly selected from patients undergoing surgical treatment of the larynx for inflammatory/ neoplastic lesions and of neck nodes. Patients underwent standard clinical workup, comprising medical history and physical examination, panendoscopy, whole-body CT scan (in cancer patients), diagnostic or therapeutic microlaryngoscopy with laryngeal biopsy, and HPV evaluation. RESULTS: The HPV analysis showed an increased risk for heavy smokers of HPV positivity, as well as precancer lesions and cancer. Type 6 and 16 seem to be prevalent in all types of laryngeal mucosa disease, but pre-neoplastic conditions versus cancer seem to show a wider variety of HPV infections while cancer patients are invariably affected by types 6 and 66. Heavy smoking is related to HPV infection likewise alcohol in association with smoking. Advanced T is more associated with HPV positivity. CONCLUSIONS: These data impose a closer follow-up of smokers and pre-neoplastic cases and the utility of the broadspectrum polymerase chain reaction assay in laryngeal dysplastic and cancer lesions. This study may allow to develop biomarkers for early detection or recurrence surveillance, to identify therapeutic targets, and to begin individualization of treatment based on the biology of these tumours. KEY WORDS: HPV infection, Larynx, Laryngeal chronic hyperplastic inflammation, Squamous cell carcinoma.

Safety and clinical activity of PD-L1 blockade in patients with aggressive recurrent respiratory papillomatosis.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a human papillomavirus (HPV)-driven disorder that causes substantial morbidity and can lead to fatal distal airway obstruction and post-obstructive pneumonias. Patients require frequent surgical debridement of disease, and no approved systemic adjuvant therapies exist. METHODS: A phase II study was conducted to investigate the clinical activity and safety of programmed death-ligand 1 (PD-L1) blockade with avelumab in patients with RRP. RESULTS: Twelve patients were treated. All patients with laryngeal RRP displayed improvement in disease burden, and 5 of 9 (56%) displayed partial responses. None of 4 patients with pulmonary RRP displayed a response. Using each patient's surgical history as their own control, patients required fewer surgical interventions after avelumab treatment (p = 0.008). A subset of partial responders developed HPV-specific reactivity in papilloma-infiltrating T-cells that correlated with reduced HPV viral load and an increased Tissue Inflammation Signature. CONCLUSIONS: Avelumab demonstrated safety and clinical activity in patients with laryngeal RRP. Further study of immune checkpoint blockade for RRP, possibly with longer treatment duration or in combination with other immunotherapies aimed at activating antiviral immunity, is warranted. TRIAL REGISTRATION: NCT, number NCT02859454 , registered August 9, 2016.

Postoperative Systemic Acyclovir in Juvenile-Onset Recurrent Respiratory Papillomatosis: The Outcome.

A prospective observational study was conducted consisting of 21 patients of Juvenile-onset recurrent respiratory papillomatosis, attending the Department of Otorhinolaryngology and Head Neck Surgery at our institution, who underwent surgical excision of the papillomas followed by oral acyclovir postoperatively. The study was aimed to observe the effect of systemic acyclovir on postoperative outcomes in children having recurrent respiratory papillomatosis undergoing primary surgical excision. It was observed that the mean interval between surgeries as well as the number of surgical interventions required was significantly lesser when acyclovir was used as a postoperative adjuvant than when surgery was done alone. Hence, the interval between successive surgeries, or in other words, the time interval between relapse of the disease could be prolonged significantly with the use of postoperative systemic acyclovir. Thus, the disease could be controlled for longer periods and repeated surgeries avoided.

Human papillomavirus types causing recurrent respiratory papillomatosis in Zimbabwe.

OBJECTIVE: Recurrent respiratory papillomatosis (RRP) caused by human papillomavirus (HPV) is preventable through vaccination. This study was motivated by the recent thrust of the Zimbabwean government to reduce incidence of HPV related cervical cancer in Zimbabwe through vaccination against HPV. We therefore set out to type HPV genotypes causing RRP in Zimbabwe. We also describe for the first time, the demographics of Zimbabwean RRP patients, the characteristics of patients with different HPV types and possible risk factors of HPV infection in our setting. METHODS: We conducted a prospective, hospital based study were patients were recruited from two national otorhinolaryngology hospitals in Zimbabwe. All patients diagnosed with RRP during a twenty four month period were included in the study. A questionnaire was administered per patient to collect both demographic and clinical variables. HPV DNA was extracted from formalin fixed paraffin embedded laryngeal tissue. The extracted HPV DNA was amplified using polymerase chain reaction and next generation sequencing was used to genotype the HPV types. RESULTS: A total of 52 patients all aged 14 years and under were recruited into the study. Only Juvenile onset RRP cases were observed over the two year period and 64% of the patients were HPV positive. HPV types 6 and 11 were the dominant types observed constituting 85% of all HPV types. The remaining 15% constituted of HPV 16 and HPV 18. 27% of the patients had coinfection with at least two different HPV types. There were no statistically significant differences between the characteristics of HPV positive and HPV negative patients. No statistically significant risk factors were observed. CONCLUSION: HPV types 6 and 11 were the predominant genotypes causing RRP in Zimbabwe. Thus the use of quadrivalent or even nonavalent HPV vaccines may play an important role in the prevention and management of RRP in Zimbabwe.

[Prevalencia y genotipos del virus del papiloma humano en muestras de tejido laríngeo de pacientes con cáncer de laringe del noreste de México]. / Prevalence and genotypes of the human papillomavirus in laryngeal tissue samples of patients with laryngeal cancer from Northeastern Mexico.

ANTECEDENTES: El cáncer de laringe representa el 21.7% de las neoplasias malignas de vías aerodigestivas superiores. La prevalencia del virus del papiloma humano (VPH) en el cáncer de laringe oscila entre el 0 y el 80%. MÉTODO: Se incluyeron 112 muestras de tejido laríngeo de pacientes con cáncer de laringe. Se amplificó el ADN y se analizó la presencia y el genotipo del VPH mediante hibridación reversa (INNO-LiPA®). Se realizaron pruebas de ji cuadrada, Fisher y t de Student no pareada. RESULTADOS: Se incluyeron muestras de 107 hombres (95.5%) y 5 mujeres (4.5%), con una edad de 65.3 ± 10.1 años, con antecedente de tabaquismo 108 (96.4%), alcoholismo 9 (8.0%) y carcinoma epidermoide moderadamente diferenciado queratinizante 96 (85.7%). Se identificó VPH en 60 (53.5%), VPH-11 en 51 (45.5%), VPH-52 en 27 (24.1%), VPH-16 en 9 (8.0%), VPH-45 en 3 (2.6%) y coinfección por más de un genotipo en 31 (27.6%). No hubo diferencia entre pacientes con y sin infección por VPH en cuanto a edad, sexo, localización, diagnóstico histopatológico, tabaquismo ni alcoholismo (p > 0.05). CONCLUSIONES: La prevalencia de infección por VPH en el cáncer de laringe fue del 53.5%, con coinfección por más de un genotipo en el 27.6%. El genotipo más frecuente fue el VPH-11, tipo de bajo riesgo, seguido por el VPH-52, de alto riesgo oncogénico. BACKGROUND: Laryngeal cancer represents 21.7% of malignancies of the upper aerodigestive tract. The prevalence of the Human Papillomavirus (HPV) in laryngeal cancer ranges 0 to 80%. METHODS: We included 112 laryngeal tissue samples obtained from patients with laryngeal cancer. DNA was extracted and amplified by PCR. HPV presence and genotype were analyzed by the reverse hybridization INNO-LiPA® assay. Chi-square, Fisher's and unpaired Student t tests were used. RESULTS: Samples from 107 male (95.5%) and 5 female patients (4.5%) were evaluated, aged 65.3±10.1 years, 108 with smoking history (96.4%), 9 with alcoholism history (8.0%), and in 96 the histological diagnosis was moderately differentiated keratinizing squamous cell carcinoma (85.7%). HPV was detected in 60 samples (53.5%), HPV-11 in 51 (45.5%), HPV-52 in 27 (24.1%), HPV-16 in 9 (8.0%), HPV-45 in 3 (2.6%), and coinfection by more than one genotype in 31 (27.6%). There was no difference between patients with and without HPV infection with respect to age, sex, tumor location and histology, smoking and alcoholism history (p>0.05). CONCLUSIONS: The prevalence of HPV infection in laryngeal cancer was 53.5% with coinfection with more than one genotype in 27.6%. The most frequent genotype was HPV-11, an oncogenic low-risk genotype, followed by HPV-52, a high-risk genotype.

An optimized methodology for whole genome sequencing of RNA respiratory viruses from nasopharyngeal aspirates.

Over the last decade, the number of viral genome sequences deposited in available databases has grown exponentially. However, sequencing methodology vary widely and many published works have relied on viral enrichment by viral culture or nucleic acid amplification with specific primers rather than through unbiased techniques such as metagenomics. The genome of RNA viruses is highly variable and these enrichment methodologies may be difficult to achieve or may bias the results. In order to obtain genomic sequences of human respiratory syncytial virus (HRSV) from positive nasopharyngeal aspirates diverse methodologies were evaluated and compared. A total of 29 nearly complete and complete viral genomes were obtained. The best performance was achieved with a DNase I treatment to the RNA directly extracted from the nasopharyngeal aspirate (NPA), sequence-independent single-primer amplification (SISPA) and library preparation performed with Nextera XT DNA Library Prep Kit with manual normalization. An average of 633,789 and 1,674,845 filtered reads per library were obtained with MiSeq and NextSeq 500 platforms, respectively. The higher output of NextSeq 500 was accompanied by the increasing of duplicated reads percentage generated during SISPA (from an average of 1.5% duplicated viral reads in MiSeq to an average of 74% in NextSeq 500). HRSV genome recovery was not affected by the presence or absence of duplicated reads but the computational demand during the analysis was increased. Considering that only samples with viral load ≥ E+06 copies/ml NPA were tested, no correlation between sample viral loads and number of total filtered reads was observed, nor with the mapped viral reads. The HRSV genomes showed a mean coverage of 98.46% with the best methodology. In addition, genomes of human metapneumovirus (HMPV), human rhinovirus (HRV) and human parainfluenza virus types 1-3 (HPIV1-3) were also obtained with the selected optimal methodology.

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.

Prevalence of human papillomavirus in benign and malignant laryngeal lesions in Egyptian patients: Cross-sectional study.

OBJECTIVE: To assess the prevalence of human papillomavirus (HPV) in benign and malignant laryngeal lesions among Egyptian patients. DESIGN: Observational analytical cross-sectional study. SETTING: Ain Shams University hospital, Otorhinolaryngology department PARTICIPANTS: Formalin-fixed paraffin-embedded specimens of 126 patients (70 benign laryngeal lesions and 56 squamous cell carcinoma lesions) were assessed for the presence of HPV DNA using MY09/11 PCR-based DNA detection. MAIN OUTCOME MEASURES: Percentage of positive samples was calculated. RESULTS: All 70 benign laryngeal lesion specimens were negative for the HPV DNA, while 2 of the 56 squamous cell carcinoma lesions (3.6%) were positive. CONCLUSIONS: The presence of HPV DNA in only two specimens in our study suggests that the proportion of laryngeal squamous cell carcinomas attributable to infection by HPV seems to be very low in Egypt.

Low prevalence of human papillomavirus in head and neck squamous cell carcinoma in the northwest region of the Philippines.

BACKGROUND: Geographic heterogeneity of human papillomavirus (HPV) involvement in head and neck squamous cell carcinoma (HNSCC) has been observed over the last few years. This trend has not been evaluated in the Philippines. Hence, this study aims to provide for the first time a data on the prevalence of HPV in HNSCC in the northwestern region of the Philippines. METHODS: Two hundred one (201) biopsy samples (179 formalin fixed paraffin embedded and 22 fresh frozen) from 163 Filipino HNSCC cases (oral cavity = 88; larynx = 60; oropharynx = 15) diagnosed between 2003 to 2013 were initially included in this study. HPV DNA was detected by two methods: (1) BSGP5+/6+-PCR/ multiplex human papillomavirus genotyping and (2) TaqMan probes-based real-time qPCR. Presence of HPV type-specific transcripts were also analyzed by reverse transcription-PCR with subsequent hybridization to oligonucleotide probes coupled to Luminex beads. Co-amplification of the ß-globin and ubiquitin C genes served as internal positive controls for DNA and RNA analyses, respectively. RESULTS AND CONCLUSIONS: Of the 163, 82 (50.3%) cases had at least one tissue sample that was valid for molecular analysis. Only two of the DNA valid cases (2.4%) were HPV DNA-positive (HPV11 and HPV33). All HPV mRNA assays rendered negative results except for HPV11 transcripts. Results of this study may indicate that there is probably very low prevalence of HPV-associated HNSCC among Filipino adults living in a rural region of the Philippines. This study could serve as a benchmark for designing follow-up studies that would assess possible changes in trends of HNSCC among Filipinos in different ethnic regions of the country, especially urban areas in which the population is expected to adapt Western style sexual behavior. A prospective sampling of fresh frozen tissue is also highly recommended to ensure better molecular analyses.

Identifying Early Target Cells of Nipah Virus Infection in Syrian Hamsters.

BACKGROUND: Nipah virus causes respiratory and neurologic disease with case fatality rates up to 100% in individual outbreaks. End stage lesions have been described in the respiratory and nervous systems, vasculature and often lymphoid organs in fatal human cases; however, the initial target organs of Nipah virus infection have not been identified. Here, we detected the initial target tissues and cells of Nipah virus and tracked virus dissemination during the early phase of infection in Syrian hamsters inoculated with a Nipah virus isolate from Malaysia (NiV-M) or Bangladesh (NiV-B). METHODOLOGY/PRINCIPAL FINDINGS: Syrian hamsters were euthanized between 4 and 48 hours post intranasal inoculation and tissues were collected and analyzed for the presence of viral RNA, viral antigen and infectious virus. Virus replication was first detected at 8 hours post inoculation (hpi). Nipah virus initially targeted type I pneumocytes, bronchiolar respiratory epithelium and alveolar macrophages in the lung and respiratory and olfactory epithelium lining the nasal turbinates. By 16 hpi, virus disseminated to epithelial cells lining the larynx and trachea. Although the pattern of viral dissemination was similar for both virus isolates, the rate of spread was slower for NiV-B. Infectious virus was not detected in the nervous system or blood and widespread vascular infection and lesions within lymphoid organs were not observed, even at 48 hpi. CONCLUSIONS/SIGNIFICANCE: Nipah virus initially targets the respiratory system. Virus replication in the brain and infection of blood vessels in non-respiratory tissues does not occur during the early phase of infection. However, virus replicates early in olfactory epithelium and may serve as the first step towards nervous system dissemination, suggesting that development of vaccines that block virus dissemination or treatments that can access the brain and spinal cord and directly inhibit virus replication may be necessary for preventing central nervous system pathology.

Cell Type- and Tissue Context-dependent Nuclear Distribution of Human Ago2.

Argonaute-2 protein (Ago2), a major component of RNA-induced silencing complex (RISC), has been viewed as a cytoplasmic protein. In this study, we demonstrated by immunofluorescence confocal microscopy that Ago2 is distributed mainly as a nuclear protein in primary human foreskin keratinocytes in monolayer cultures and their derived organotypic (raft) cultures, although it exhibits only a minimal level of nuclear distribution in continuous cell lines such as HeLa and HaCaT cells. Oncogenic human papillomavirus type 16 (HPV16) or type 18 (HPV18) infection of the keratinocytes does not affect the nuclear Ago2 distribution. Examination of human tissues reveals that Ago2 exhibits primarily as a nuclear protein in skin, normal cervix, and cervical cancer tissues, but not in larynx. Together, our data provide the first convincing evidence that the subcellular distribution of Ago2 occurs in a cell type- and tissue context-dependent manner and may correlate with its various functions in regulation of gene expression.

Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice.

Chloroviruses (family Phycodnaviridae) are large DNA viruses known to infect certain eukaryotic green algae and have not been previously shown to infect humans or to be part of the human virome. We unexpectedly found sequences homologous to the chlorovirus Acanthocystis turfacea chlorella virus 1 (ATCV-1) in a metagenomic analysis of DNA extracted from human oropharyngeal samples. These samples were obtained by throat swabs of adults without a psychiatric disorder or serious physical illness who were participating in a study that included measures of cognitive functioning. The presence of ATCV-1 DNA was confirmed by quantitative PCR with ATCV-1 DNA being documented in oropharyngeal samples obtained from 40 (43.5%) of 92 individuals. The presence of ATCV-1 DNA was not associated with demographic variables but was associated with a modest but statistically significant decrease in the performance on cognitive assessments of visual processing and visual motor speed. We further explored the effects of ATCV-1 in a mouse model. The inoculation of ATCV-1 into the intestinal tract of 9-11-wk-old mice resulted in a subsequent decrease in performance in several cognitive domains, including ones involving recognition memory and sensory-motor gating. ATCV-1 exposure in mice also resulted in the altered expression of genes within the hippocampus. These genes comprised pathways related to synaptic plasticity, learning, memory formation, and the immune response to viral exposure.

Laryngeal papillomatosis associated dysplasia in the adult population: an update on prevalence and HPV subtyping.

OBJECTIVES: The objectives were to determine the prevalence of laryngeal dysplasia and associated human papilloma virus (HPV) subtypes in adult patients, 18 years or older, suffering from laryngeal papillomatosis at a tertiary care institution. STUDY DESIGN: Retrospective cohort study. METHODS: Patients with biopsy proven laryngeal papillomatosis were identified via chart review. All available pathology specimens were reviewed by a dedicated head and neck pathologist to confirm/refute the diagnosis of laryngeal dysplasia, and grade the level of dysplasia. Interrater agreement was compared using cross-tabulation methods. Specimens identified to be positive for dysplasia underwent further testing via in situ hybridization for low-risk (6/11) or high-risk (16/18) HPV subtypes. RESULTS: Of the 85 subjects identified to have laryngeal papillomatosis, 24(28%) demonstrated laryngeal dysplasia. There was good interrater agreement on the presence of dysplasia; however, there was only fair agreement on the grade of dysplasia. Of the pathology specimens tested for HPV subtype, the majority of patients (62%) were positive for HPV 6/11, including all high-grade dysplasia patients. Three (12%) dysplasia specimens were negative for both high- and low-risk HPV subtypes. CONCLUSIONS: We found a 28% prevalence of dysplasia in our patient population with the majority of patients positive for low-risk HPV subtypes indicating that high-risk HPV subtypes do not predispose laryngeal papilloma patients to dysplasia.