scholarly journals HPV Strain Predicts Severity of Juvenile-Onset Recurrent Respiratory Papillomatosis with Implications for Disease Screening

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2556
Author(s):  
Mary C. Bedard ◽  
Alessandro de Alarcon ◽  
Yann-Fuu Kou ◽  
David Lee ◽  
Alexandra Sestito ◽  
...  
Keyword(s):  
Gene Expression ◽  
Disease Severity ◽  
Disease Onset ◽  
Tissue Bank ◽  
Benign Neoplasm ◽  
Recurrent Respiratory Papillomatosis ◽  
Clinical Severity ◽  
Viral Gene ◽  
Juvenile Onset ◽  
Severity Scores

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is the most common benign neoplasm of the larynx in children, presenting with significant variation in clinical course and potential for progression to malignancy. Since JoRRP is driven by human papillomavirus (HPV), we evaluated viral factors in a prospective cohort to identify predictive factors of disease severity. Twenty children with JoRRP undergoing routine debridement of papillomas were recruited and followed for ≥1 year. Demographical features, clinical severity scores, and surgeries over time were tabulated. Biopsies were used to establish a tissue bank and primary cell cultures for HPV6 vs. HPV11 genotyping and evaluation of viral gene expression. We found that patients with HPV11+ disease had an earlier age at disease onset, higher frequency of surgeries, increased number of lifetime surgeries, and were more likely to progress to malignancy. However, the amplitude of viral E6/E7 gene expression did not account for increased disease severity in HPV11+ patients. Determination of HPV strain is not routinely performed in the standard of care for JoRRP patients; we demonstrate the utility and feasibility of HPV genotyping using RNA-ISH for screening of HPV11+ disease as a biomarker for disease severity and progression in JoRRP patients.

scholarly journals Alpha, Beta, and Gamma HPV Infection in Juvenile Onset Recurrent Respiratory Papillomatosis

2021 ◽  
Author(s):  
Martina Bertinazzi ◽  
Tarik Gheit ◽  
Jerry Polesel ◽  
Sandrine McKay-Chopin ◽  
Cesare Cutrone ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Hpv Infection ◽  
Recurrent Respiratory Papillomatosis ◽  
Small Sample ◽  
Clinical Severity ◽  
Laser Vaporization ◽  
Double Infection ◽  
Juvenile Onset ◽  
Hpv Dna ◽  
Alpha Beta

Abstract Purpose The aim of our study is to evaluate the prevalence of different HPV genera – alpha, beta and gamma – in Juvenile onset Recurrent Respiratory Papillomatosis (JoRRP) and examine the association of type and genus-specific viral features with the clinical outcome of disease. Methods This retrospective observational study includes consecutive patients with JoRRP who were treated in a referral centre between October 2000 and October 2020. All patients underwent cold excision and laser vaporization of papillomatous lesions. Samples were analysed for the presence of 120 viral genotypes (22 alpha-HPV, 46 beta-HPV, 52 gamma-HPV) using a highly sensitive multiplex genotyping assay. Results Twenty patients with JoRRP, aged 0.3–11 years old, were included, with a median follow-up of 13.5 years. All samples were HPV DNA positive: 20 (100%) for alpha-HPV DNA; 7 (35%) for beta – HPV DNA; 0 for gamma-HPV DNA. Three groups were defined according to the number of infections: seven cases (35%) with HPV mono-infection; ten cases (50%) with HPV double-infection; three cases (15%) with ≥ 3 HPV infections. At diagnosis, patients with ≥ 3 HPV infections reported higher median Derkay’s score than those with mono-infection (21 vs 14, P = 0.018). Number of HPV infections was also associated with clinical outcomes, with an average of 0.5 surgical procedures/year in patients with mono-infection, 1.2 for double-infection, 2.6 for ≥ 3 infections (P = 0.006). Conclusion Despite the small sample size, these preliminary data support an association between the number of different alpha and beta HPV co-infections and the clinical severity of the disease.

Distribution Characteristics of Juvenile-Onset Recurrent Respiratory Papillomatosis at First-Time Surgery

2021 ◽  
pp. 014556132110498
Author(s):  
Xiaoli Qu ◽  
Yang Xiao ◽  
Lijing Ma ◽  
Jun Wang
Keyword(s):  
Vocal Cord ◽  
Disease Severity ◽  
Recurrent Respiratory Papillomatosis ◽  
Age At Diagnosis ◽  
Juvenile Onset ◽  
Vocal Cords ◽  
Younger Age ◽  
False Vocal ◽  
The Impact ◽  
First Time

Objectives The lesion distribution of juvenile-onset recurrent respiratory papillomatosis (JORRP) during first-time surgery has been rarely reported. The purpose of this study was to describe the anatomical distribution of papilloma across 25 Derkay sites during initial surgery and to assess the impact of the lesion distribution on disease severity. Methods Surgical videos and medical records of 106 patients with JORRP (27 aggressive and 79 nonaggressive cases) were retrospectively reviewed. Lesion locations were recorded using Derkay anatomical sites. Logistic regression was used to analyze the effect of the lesion distribution on disease severity. Results Among the 106 patients, the true vocal cords (90.6% left, 84.0% right) were the most frequently involved site, followed by the false vocal cords (39.6% left, 35.8% right) and the anterior commissure (26.4%). Two patients (1.9%) had tracheal involvement. Patients with false vocal cord involvement (odds ratio [OR] = 3.425, 95% confidence interval [CI] [1.285, 9.132], P = .014) and a younger age at diagnosis (OR = .698, 95% CI [.539, .905], P = .007) were more likely to require more than 4 procedures in the year following first-time surgery. Conclusions Lesions were most common on the true vocal cords. False vocal cord involvement and a younger age at diagnosis were risk factors for disease severity.

scholarly journals Type 1 FSHD with 6–10 Repeated Units: Factors Underlying Severity in Index Cases and Disease Penetrance in Their Relatives Attention

2020 ◽  
Vol 21 (6) ◽  
pp. 2221
Author(s):  
Emmanuelle Salort-Campana ◽  
Farzad Fatehi ◽  
Sadia Beloribi-Djefaflia ◽  
Stéphane Roche ◽  
Karine Nguyen ◽  
...  
Keyword(s):  
Disease Severity ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Clinical Severity ◽  
Cross Sectional ◽  
Repeat Array ◽  
D4z4 Repeat ◽  
Severity Scores ◽  
Group 2 ◽  
Group 1

Molecular defects in type 1 facioscapulohumeral muscular dystrophy (FSHD) are caused by a heterozygous contraction of the D4Z4 repeat array from 1 to 10 repeat units (RUs) on 4q35. This study compared (1) the phenotype and severity of FSHD1 between patients carrying 6–8 vs. 9–10 RUs, (2) the amount of methylation in different D4Z4 regions between patients with FSHD1 with different clinical severity scores (CSS). This cross-sectional multicenter study was conducted to measure functional scales and for genetic analysis. Patients were classified into two categories according to RUs: Group 1, 6–8; Group 2, 9–10. Methylation analysis was performed in 27 patients. A total of 99 carriers of a contracted D4Z4 array were examined. No significant correlations between RUs and CSS (r = 0.04, p = 0.73) and any of the clinical outcome scales were observed between the two groups. Hypomethylation was significantly more pronounced in patients with high CSS (>3.5) than those with low CSS (<1.5) (in DR1 and 5P), indicating that the extent of hypomethylation might modulate disease severity. In Group 1, the disease severity is not strongly correlated with the allele size and is mostly correlated with the methylation of D4Z4 regions.

Is intralesional cidofovir worthwhile in juvenile recurrent respiratory papillomatosis?

2006 ◽  
Vol 120 (7) ◽  
pp. 561-565 ◽  
Author(s):  
P Sheahan ◽  
S Sexton ◽  
J D Russell
Keyword(s):  
Disease Severity ◽  
Severity Score ◽  
Prospective Observational Study ◽  
Recurrent Respiratory Papillomatosis ◽  
Prolonged Treatment ◽  
Disease Remission ◽  
Treatment Regimes ◽  
Severity Scores ◽  
Surgical Debulking ◽  
Reduce Disease Severity

Objective: To investigate the efficacy of intralesional cidofovir in the treatment of recurrent respiratory papillomatosis (RRP) in children.Methods: Prospective observational study of four consecutive children with RRP treated at an academic tertiary children's hospital. Laryngo-bronchoscopy was performed at three- to five-weekly intervals. Photodocumentation was obtained and disease severity assessed using an anatomical RRP severity score. Surgical debulking of large papillomas was then performed, and cidofovir (5 mg/ml) injected into any remaining papillomas as well as submucosally at the sites of resected papillomas. The efficacy of cidofovir was assessed by the change in papilloma severity score over the course of the treatment.Results: Complete disease remission was obtained in one patient, with a partial response seen in two others. One patient showed no significant response. The greatest beneficial effect was seen after the fourth cidofovir injection; however, two patients demonstrated a deterioration in severity scores after treatment was withheld at this point. Both responded well to further cidofovir injections. However, a clear plateau in the response to cidofovir was seen in all patients by the eighth injection.Conclusion: Intralesional cidofovir may help control papilloma regrowth and reduce disease severity in many children with RRP. In most cases, cidofovir would appear to be less efficacious in causing disease eradication. There appears to be little evidence to support prolonged treatment regimes (i.e. more than eight treatments).

Gene expression in canine atopic dermatitis and correlation with clinical severity scores

2009 ◽  
Vol 55 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Shona H. Wood ◽  
Dylan N. Clements ◽  
William E. Ollier ◽  
Tim Nuttall ◽  
Neil A. McEwan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Atopic Dermatitis ◽  
Clinical Severity ◽  
Canine Atopic Dermatitis ◽  
Severity Scores

Comparison of Cidofovir and the Measles, Mumps, and Rubella Vaccine in the Treatment of Recurrent Respiratory Papillomatosis

2017 ◽  
Vol 96 (2) ◽  
pp. 69-74 ◽  
Author(s):  
Ryan Kent Meacham ◽  
Jerome W. Thompson
Keyword(s):  
Disease Severity ◽  
Demographic Data ◽  
Recurrent Respiratory Papillomatosis ◽  
Adjunctive Treatment ◽  
Mmr Vaccine ◽  
Severity Scores ◽  
Remission Rates ◽  
Study Population ◽  
Group 3 ◽  
Disease Severity Scores

We conducted a retrospective study of the use of cidofovir and the measles, mumps, and rubella (MMR) vaccineas adjunctive treatments to lesion debridement in patients with recurrent respiratory papillomatosis (RRP). Our study population was made up of 15 children—7 boys and 8 girls, aged 1 to 16 years at diagnosis (mean: 6.2)—with pathologically confirmed RRP who had been followed for at least 1 year. In addition to demographic data, we compiled information on disease severity, the type of adjunctive treatment administered to each patient, the frequency of debridements, the length of observation, and remission rates. Of the 15 patients, 5 had been treated with cidofovirafter debridement (cidofovir-only group), 6 were treated with MMR vaccine after debridement (MMR-only group), 3 were treated with one and later switched to the other based on parental preference, and 1 received neither treatment, only debridement. The initial mean Derkay disease severity scores were 12.6 for the cidofovir-only group and 11.0 for the MMR-only group (p = 0.61). The cidofovir-only patients underwent an average of 11.8 adjunctive treatments and the MMR-only patients an average of 17.7 (p = 0.33). The average duration of observation was 44.0 months in the cidofovir-only group and 64.7 months in the MMR-only group (p = 0.29). Remission rates were 20% in the cidofovir-only group and 50% in the MMR-only group (p = 0.54). Our study found insufficient evidence of any significant differences between cidofovir and the MMR vaccinein terms of the number and frequency of adjunctive treatments and the rates of remission.

scholarly journals P.007 Onset of facial weakness correlated with muscle strength in infantile facioscapulohumeral dystrophy (FSHD)

2016 ◽  
Vol 43 (S2) ◽  
pp. S23-S23
Author(s):  
JK Mah ◽  
J Feng ◽  
C Carty ◽  
Y Chen ◽  
T Duong ◽  
...  
Keyword(s):  
Muscle Strength ◽  
Disease Severity ◽  
Age At Onset ◽  
Clinical Severity ◽  
Manual Muscle Testing ◽  
Shoulder Abduction ◽  
Facial Weakness ◽  
Muscle Involvement ◽  
Muscle Testing ◽  
Severity Scores

Background: We investigated motor function associations with age, gender, and D4Z4 fragment size among participants with infantile FSHD. Methods: We collected standardized motor assessments including goniometry, manual muscle testing (MMT), quantitative muscle testing (QMT), and FSHD clinical severity scores (CSS) at 12 CINRG sites. To measure associations, we used linear regression models adjusted for age at enrollment, onset of weakness, gender, and D4Z4 repeats. Results: 53 participants (59% female, mean age 23.1±14.6 years) were enrolled. Weakness was most pronounced at the shoulder girdle and rectus abdominis (median MMT 30-38% of normal). Older enrollment age was associated with greater CSS (p=0.005) and reduced range of motion in shoulder abduction, shoulder flexion, elbow flexion, and ankle dorsiflexion (all p<0.01). Females and participants with larger D4Z4 repeats had milder shoulder/arm weakness and lesser disease severity (all p<0.05). Increased age at onset of facial weakness was significantly associated with greater total muscle strength, as measured by QMT and MMT (both p=0.002). Conclusions: We confirm the descending pattern of muscle involvement and milder disease severity in females or those with larger D4Z4 repeats. Furthermore, earlier age at onset of facial weakness was associated with greater muscle weakness. Future longitudinal assessments will describe rates of disease progression in this population.

scholarly journals Clinical implications of alpha, beta, and gamma HPV infection in juvenile onset recurrent respiratory papillomatosis

2021 ◽  
Author(s):  
Martina Bertinazzi ◽  
Tarik Gheit ◽  
Jerry Polesel ◽  
Sandrine McKay-Chopin ◽  
Cesare Cutrone ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Hpv Infection ◽  
Recurrent Respiratory Papillomatosis ◽  
Small Sample ◽  
Clinical Severity ◽  
Double Infection ◽  
Juvenile Onset ◽  
Hpv Dna ◽  
Alpha Beta ◽  
Severity Of The Disease

Abstract Purpose The aim of our study was to evaluate the prevalence of different HPV genera—alpha, beta and gamma—in Juvenile onset Recurrent Respiratory Papillomatosis (JoRRP) and examine the association of type and genus-specific viral features with the clinical outcome of disease. Methods This retrospective observational study included consecutive patients with JoRRP who were treated in a referral centre between October 2000 and October 2020. All patients underwent cold excision and laser vaporisation of papillomatous lesions. Samples were analysed for the presence of 120 viral genotypes (22 alpha-HPV, 46 beta-HPV, 52 gamma-HPV) using a highly sensitive multiplex genotyping assay. Results Twenty patients with JoRRP, aged 0.3–11 years, were included, with a median follow-up of 13.5 years. All samples were HPV DNA positive: 20 (100%) for alpha-HPV DNA; 7 (35%) for beta—HPV DNA; 0 for gamma-HPV DNA. Three groups were defined according to the number of infections: seven cases (35%) with HPV mono-infection; ten cases (50%) with HPV double-infection; three cases (15%) with ≥ 3 HPV infections. At diagnosis, patients with ≥ 3 HPV infections reported higher median Derkay’s score than those with mono-infection (21 vs 14, P = 0.018). Number of HPV infections was also associated with clinical outcomes, with an average of 0.5 surgical procedures/year in patients with mono-infection, 1.2 for double-infection, 2.6 for ≥ 3 infections (P = 0.006). Conclusion Despite the small sample size, these preliminary data support an association between the number of different alpha and beta HPV co-infections and the clinical severity of the disease.

scholarly journals Patient-Derived Organotypic Epithelial Rafts Model Phenotypes in Juvenile-Onset Recurrent Respiratory Papillomatosis

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 68
Author(s):  
Mary C. Bedard ◽  
Marion G. Brusadelli ◽  
Adrean Carlile ◽  
Sonya Ruiz-Torres ◽  
Hannah Lodin ◽  
...  
Keyword(s):  
Viral Gene Expression ◽  
Recurrent Respiratory Papillomatosis ◽  
Model Systems ◽  
Viral Gene ◽  
Cell Contact ◽  
Basal Cells ◽  
Disease Pathogenesis ◽  
Juvenile Onset ◽  
Monolayer Cultures ◽  
Shed Light

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is driven by human papillomavirus (HPV) low-risk strains and is associated with significant morbidity. While previous studies of 2D cultures have shed light on disease pathogenesis and demonstrated the utility of personalized medicine approaches, monolayer cultures lack the 3D tissue architecture and physiology of stratified, sequentially differentiated mucosal epithelium important in RRP disease pathogenesis. Herein we describe the establishment of JoRRP-derived primary cell populations that retain HPV genomes and viral gene expression in culture. These were directly compared to cells from matched adjacent non-diseased tissue, given the known RRP patient-to-patient variability. JoRRP papilloma versus control cells displayed decreased growth at subconfluency, with a switch to increased growth after reaching confluency, suggesting relative resistance to cell-cell contact and/or differentiation. The same papilloma cells grown as 3D organotypic rafts harbored hyperproliferation as compared to controls, with increased numbers of proliferating basal cells and inappropriately replicating suprabasal cells, mimicking phenotypes in the patient biopsies from which they were derived. These complementary model systems provide novel opportunities to elucidate disease mechanisms at distinct stages in JoRRP progression and to identify diagnostic, prognostic and therapeutic factors to personalize patient management and treatment.

scholarly journals Mortality prediction in sepsis via gene expression analysis: a community approach

2016 ◽  
Author(s):  
Timothy E Sweeney ◽  
Thanneer M Perumal ◽  
Ricardo Henao ◽  
Marshall Nichols ◽  
Judith A Howrylak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Risk Stratification ◽  
Unmet Need ◽  
Predictive Performance ◽  
Mortality Prediction ◽  
Clinical Severity ◽  
Prognostic Models ◽  
Improve Risk Stratification ◽  
Severity Scores ◽  
Community Onset

AbstractImproved risk stratification and prognosis in sepsis is a critical unmet need. Clinical severity scores and available assays such as blood lactate reflect global illness severity with suboptimal performance, and do not specifically reveal the underlying dysregulation of sepsis. Here three scientific groups were invited to independently generate prognostic models for 30-day mortality using 12 discovery cohorts (N=650) containing transcriptomic data collected from primarily community-onset sepsis patients. Predictive performance was validated in 5 cohorts of community-onset sepsis patients (N=189) in which the models showed summary AUROCs ranging from 0.765-0.89. Similar performance was observed in 4 cohorts of hospital-acquired sepsis (N=282). Combining the new gene-expression-based prognostic models with prior clinical severity scores led to significant improvement in prediction of 30-day mortality (p<0.01). These models provide an opportunity to develop molecular bedside tests that may improve risk stratification and mortality prediction in patients with sepsis, improving both resource allocation and prognostic enrichment in clinical trials.

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