Juvenile-onset Recurrent Respiratory Papillomatosis Research Articles

Age of onset of recurrent respiratory papillomatosis: a distribution analysis.

Distribution of age of onset of recurrent respiratory papillomatosis (RRP) is generally described to be bimodal, with peaks at approximately 5 years and 30 years. This assumption has never been scientifically confirmed, and authors tend to refer to an article that does not describe distribution. Knowledge of the distribution of age of onset is important for virological and epidemiological comprehension. The objective of this study was to determine the distribution of age of onset of RRP in a large international sample. Cross-sectional distribution analysis. Laryngologists from 12 European hospitals provided information on date of birth and date of onset of all their RRP patients treated between 1998 and 2012. Centers that exclusively treated either patients with juvenile onset RRP or patients with adult onset RRP, or were less accessible for one of these groups, were excluded to prevent skewness. A mixture model was implemented to describe distribution of age of onset. The best fitting model was selected using the Bayesian information criterion. Six hundred and thirty-nine patients were included in the analysis. Age of onset was described by a three component mixture distribution with lognormally distributed components. Recurrent respiratory papillomatosis starts at three median ages 7, 35 and 64 years. Distribution of age of onset of RRP shows three peaks. In addition to the already adopted idea of age peaks at paediatric and adult age, there is an additional peak around the age of 64.

Effectiveness of the human papillomavirus (types 6, 11, 16, and 18) vaccine in the treatment of children with recurrent respiratory papillomatosis

ObjectiveTo evaluate whether the quadrivalent human papillomavirus (HPV) (types 6, 11, 16, and 18) vaccine influences the clinical course of juvenile-onset recurrent respiratory papillomatosis (RRP) when administered to a group of patients with this condition. MethodsUncontrolled intervention study of patients with juvenile-onset RRP examined at the Pediatric Otorhinolaryngology Clinic, Federal University of São Paulo, where nine patients between the ages of nine and 17 received three doses of the prophylactic quadrivalent HPV vaccine (Gardasil®) and were followed for one year. Disease staging, intervals between relapses, intervals between surgeries, and the number of surgeries during the year prior to vaccination and during the first year after vaccination were compared. ResultsEight patients were infected with HPV-6 and one with HPV-11. There were no statistically significant differences in the clinical scores (p=0.083), anatomical scores (p=0.257), intervals between relapses (p=0.062), intervals between surgeries (p=0.357), or the numbers of surgeries (p=0.180) when the years before and after vaccination were compared. All patients had relapses following vaccination. ConclusionPatients with juvenile-onset RRP experienced a similar clinical course in the year after versus the year before vaccination with Gardasil®.

Role of bevacizumab in juvenile onset recurrent respiratory papillomatosis

Role of bevacizumab in juvenile onset recurrent respiratory papillomatosis

Risk Factors for Dysplasia in Recurrent Respiratory Papillomatosis in an Adult and Pediatric Population.

Recurrent respiratory papillomatosis (RRP) is classically described as a benign neoplasm of the larynx caused by the low-risk human papillomavirus (HPV) viral subtypes. Nevertheless, transformation to dysplasia and invasive carcinoma can occur. We aimed to assess the prevalence of dysplasia and carcinoma-ex-papilloma in both adult-onset and juvenile-onset RRP and identify patient risk factors for this dysplastic transformation. Ten-year retrospective chart review of a tertiary otolaryngology referral center. Patients with papilloma were identified from a review of a pathology database and clinical records. Patient demographics, pathologic data, and treatment history, including use of cidofovir as an adjunctive therapy for papilloma, were extracted from electronic medical records. One hundred fifty-nine RRP patients were identified, 96 adult-onset (AORRP) and 63 juvenile-onset (JORRP) cases. Of this cohort, 139 (87%) had only benign papilloma as a pathologic diagnosis. In the AORRP cohort, 10 patients (10%) were diagnosed with dysplasia or carcinoma in situ in addition to papilloma, and 5 patients (5%) had malignant transformation to invasive carcinoma-ex-papilloma. There was a significantly higher age of disease onset for those with dysplasia or carcinoma versus those without dysplasia or carcinoma (56 vs 45 years old; P = .0005). Of the 63 JORRP patients, there were no cases of dysplasia but 3 (5%) cases of invasive carcinoma-ex-papilloma, all involving pulmonary disease. The JORRP patients with carcinoma-ex-papilloma had a younger average disease onset (2 vs 6 years old; P = .009) and a higher rate of tracheal involvement than those without carcinoma. Gender, smoking history, number of operations, or use of cidofovir showed no association with the development of dysplasia or carcinoma-ex-papillomatosis in either the AORRP or JORRP population. In a large series of RRP, age of disease onset is the strongest predictor of dysplastic transformation in the adult and pediatric population. Carcinoma-ex-papillomatosis was uniformly associated with pulmonary disease in the JORRP population in this series. No other demographic or behavioral factors, including adjunctive therapy with cidofovir, were statistically associated with dysplasia or carcinoma-ex-papilloma.

O16.4 The estimated impact and cost-effectiveness of nonavalent hpv vaccination in the united states

Introduction The objective of this study was to assess the health impact and cost-effectiveness of human papillomavirus (HPV) vaccination strategies in the United States. Specifically, we examined the incremental costs and benefits of the 9-valent HPV vaccine (9vHPV) compared to the quadrivalent HPV vaccine (4vHPV). Like 4vHPV, 9vHPV protects against HPV types 6, 11, 16, and 18. 9vHPV also protects against 5 additional HPV types 31, 33, 45, 52, and 58. Methods We adapted a previously published model of the impact and cost-effectiveness of 4vHPV to include the five additional HPV types in 9vHPV. The vaccine strategies we examined were (1) 4vHPV for males and females; (2) 9vHPV for females and 4vHPV for males; and (3) 9vHPV for males and females. In the base case, we assumed 9vHPV cost $13 more per dose than 4vHPV. Our model included a wide range of HPV-associated health outcomes that could potentially be averted by vaccination: cervical intraepithelial neoplasia; genital warts; juvenile-onset recurrent respiratory papillomatosis; and cervical, vaginal, vulvar, anal, oropharyngeal, and penile cancers Results Compared to no vaccination, 4vHPV for both sexes cost $5,100 to $22,300 (in 2013 US dollars) per quality-adjusted life year (QALY) depending on assumptions regarding vaccine coverage and 4vHPV cross-protection against HPV 31, 33, 45, 52, and 58. Providing 9vHPV for females instead of 4vHPV was cost-saving in most scenarios we examined. The cost per QALY gained by providing 9vHPV to males instead of 4vHPV varied substantially depending on assumptions such as vaccine coverage and cross-protection of 4vHPV. However, the strategy of 9vHPV for both sexes (compared to the strategy of 4vHPV for both sexes) was cost-saving under most scenarios. Conclusion A vaccination program of 9vHPV for both sexes can save money and improve health outcomes compared to a vaccination program of 4vHPV for both sexes. Disclosure of interest statement The authors have no conflicts to declare. No pharmaceutical grants were received in the development of this study.

Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis

A significant proportion of recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus type 6 (HPV-6). The long control region (LCR) contains cis-elements for regulation of transcription. Our aim was to characterize LCR HPV-6 variants in RRP cases, compare promoter activity of these isolates and search for cellular transcription factors (TFs) that could explain the differences observed. The complete LCR from 13 RRP was analyzed. Transcriptional activity of 5 variants was compared using luciferase assays. Differences in putative TFs binding sites among variants were revealed using the TRANSFAC database. Chromatin immunoprecipation (CHIP) and luciferase assays were used to evaluate TF binding and impact upon transcription, respectively. Juvenile-onset RRP cases harbored exclusively HPV-6vc related variants, whereas among adult-onset cases HPV-6a variants were more prevalent. The HPV-6vc reference was more transcriptionally active than the HPV-6a reference. Active FOXA1, ELF1 and GATA1 binding sites overlap variable nucleotide positions among isolates and influenced LCR activity. Furthermore, our results support a crucial role for ELF1 on transcriptional downregulation. We identified TFs implicated in the regulation of HPV-6 early gene expression. Many of these factors are mutated in cancer or are putative cancer biomarkers, and must be further studied.

The incidence and prevalence of juvenile-onset recurrent respiratory papillomatosis in the Free State province of South Africa and Lesotho

Background and objective: Although the estimated incidence and prevalence of juvenile-onset recurrent respiratory papillomatosis (JORRP) has been determined in countries in North America and Europe and in Australia, no studies have attempted to determine the incidence or prevalence of JORRP in African countries. The aim of this study is to determine the incidence and prevalence of JORRP in the Free State province of South Africa and Lesotho. MethodsThis was a retrospective study in which the records of all patients with JORRP from the Free State province of South Africa or Lesotho treated at Universitas Academic Hospital or by otorhinolaryngologists in private practice between 1 January 2011 and 31 December 2013 were reviewed. ResultsThe estimated incidence and prevalence of JORRP in the Free State were 1.34 and 3.88 per 100,000 population respectively while the estimated incidence and prevalence in Lesotho were 0.49 and 1.04 per 100,000 population respectively. However, these figures are probably an underestimation. ConclusionThe incidence and prevalence calculated for the Free State were generally higher than those found in other studies, while those calculated for Lesotho was similar to those obtained in other studies.

Estimating the incidence and prevalence of juvenile-onset recurrent respiratory papillomatosis in publicly and privately insured claims databases in the United States.

Juvenile-onset recurrent respiratory papillomatosis (JORRP) is a chronic disease caused by human papillomavirus types 6 and 11. It is associated with significant morbidity that places intense physical, psychological, and financial strain on patients and their families. Few studies have assessed the incidence and prevalence of JORRP in the United States. This retrospective, longitudinal cohort study was performed using data from a pair of large insurance claims databases in the United States. The Optum Clinformatics and Truven MarketScan Medicaid databases represent a sample of privately and publicly insured children, respectively. Cohorts of children aged 0 to 17 years were created within each database to estimate the incidence and prevalence of JORRP in 2006. Claims-based algorithms were designed to capture as many potential cases as possible. To improve the accuracy of the incidence and prevalence estimates, chart validation was performed to estimate the positive predictive value (PPV) of the claims-based algorithms. The overall PPV-adjusted incidence of JORRP in 2006 was 0.51 per 100,000 in Optum and 1.03 per 100,000 in the MarketScan Medicaid population. Peak incidence was observed among 0- to 4-year-olds in both databases. The PPV-adjusted prevalence of JORRP in 2006 was 1.45 and 2.93 per 100,000 in the Optum and MarketScan Medicaid cohorts, respectively. Although relatively uncommon, JORRP represents a disease with significant morbidity. The incidence and prevalence of JORRP in publicly insured children were consistently higher than those covered by private insurance plans, suggesting an increased burden of illness among those with lower socioeconomic status.

A Case for Immunization of Human Papillomavirus (HPV) 6/11-Infected Pregnant Women With the Quadrivalent HPV Vaccine to Prevent Juvenile-Onset Laryngeal Papilloma

Juvenile-onset recurrent respiratory papillomatosis (JORRP) is a rare disease caused by intrapartum or perinatal transmission of human papillomavirus (HPV) types 6 and 11 from an infected mother to the newborn. Immunization of a pregnant woman who has condyloma or HPV-6/11 infection with the quadrivalent HPV vaccine will result in a high neutralizing antibody response to HPV 6 and HPV 11 in her serum, and these antibodies transferred to the newborn will likely protect the child against the development of JORRP. Because of the low incidence of disease in at-risk children, it may be difficult to test the effectiveness of maternal immunization for prevention of JORRP.

Clinical efficiency of quadrivalent HPV (types 6/11/16/18) vaccine in patients with recurrent respiratory papillomatosis

The aim of the study was to assess the clinical efficiency of quadrivalent HPV (types 6/11/16/18) vaccine in patients with recurrent respiratory papillomatosis (RRP). This was a prospective study of patients with RRP treated from January 2009 to July 2012 at the Ear, Nose and Throat Department of the Emergency County Hospital of Cluj-Napoca, Romania. Demographic characteristics, onset of RRP, HPV typing, use and number of cidofovir injections, number of surgeries for RRP per year, and use of human papillomavirus vaccine (types 6, 11, 16, 18) (recombinant, adsorbed)/Silgard® were considered from all the patients included in the study. Charts were reviewed for follow-up after diagnosis, after cidofovir, and after Silgard; all the statistical tests were applied at a significance level of 5%. The recurrences were observed within 27.53 ± 11.24 days after intralesional cidofovir injection. Thirteen patients with recurrence after cidofovir agreed and received Silgard® vaccine. 85% [54.44–99.41] of patients had no recurrences during 1-year follow-up. The recurrence of papillomas was observed in two patients (15%, 95% CI [0.59–45.56]), one with adult-onset RRP and one with juvenile-onset RRP. Both recurrences appeared after the first Silgard dose; one month after the third vaccine dose each patient underwent a new surgery for remaining papillomas with no recurrences at 1-year follow-up visit. Silgard® vaccination had a good effect and proved to be efficient in the treatment of our patients with RRR without appearance of recurrence in 85% of the patients during 1-year follow-up.

Nawracająca brodawczakowatość układu oddechowego – epidemiologia i charakterystyka infekcji HPV u dzieci

Recurrent respiratory papillomatosis (RRP) is the most common non-malignant neoplastic respiratory tract disease in children. Main symptoms are related to the periods of recurrent growth of multiple exophytic nodules covering the surface of the mucosa interfering with the patency of the airways. The connection between juvenile onset recurrent respiratory papillomatosis (JORRP) and human papillomavirus (HPV) infection is undisputable and clearly confirmed.Actual epidemiological studies display the relationship between the disease in a child and a low socio-economic status of a family, mother's young age, sexual activity of parents measured by the number of sexual partners before a child's birth and clinically obvious HPV infections in mother or father.RRP in children may be mild and self-limiting or aggressive in character, with a poor prognosis. The papillomas may spread throughout the entire respiratory tree, but most often involve the larynx. Recurrent respiratory papillomatosis causes hoarseness (that may progress to aphonia) and upper respiratory obstruction. The chronic curse of the disease always unfavourably affects the patient's quality of life.Laboratory diagnosis of HPV infections is dependent upon molecular techniques such as DNA hybridization or nucleic acid amplification. Routine application of molecular techniques such as PCR for detection and analysis of HPVs in patients with RRP has diagnostic and prognostic significance.

Integration of HPV6 and Downregulation of AKR1C3 Expression Mark Malignant Transformation in a Patient with Juvenile-Onset Laryngeal Papillomatosis

Juvenile-onset recurrent respiratory papillomatosis (RRP) is associated with low risk human papillomavirus (HPV) types 6 and 11. Malignant transformation has been reported solely for HPV11-associated RRP in 2–4% of all RRP-cases, but not for HPV6. The molecular mechanisms in the carcinogenesis of low risk HPV-associated cancers are to date unknown. We report of a female patient, who presented with a laryngeal carcinoma at the age of 24 years. She had a history of juvenile-onset RRP with an onset at the age of three and subsequently several hundred surgical interventions due to multiple recurrences of RRP. Polymerase chain reaction (PCR) or bead-based hybridization followed by direct sequencing identified HPV6 in tissue sections of previous papilloma and the carcinoma. P16INK4A, p53 and pRb immunostainings were negative in all lesions. HPV6 specific fluorescence in situ hybridization (FISH) revealed nuclear staining suggesting episomal virus in the papilloma and a single integration site in the carcinoma. Integration-specific amplification of papillomavirus oncogene transcripts PCR (APOT-PCR) showed integration in the aldo-keto reductase 1C3 gene (AKR1C3) on chromosome 10p15.1. ArrayCGH detected loss of the other gene copy as part of a deletion at 10p14-p15.2. Western blot analysis and immunohistochemistry of the protein AKR1C3 showed a marked reduction of its expression in the carcinoma. In conclusion, we identified a novel molecular mechanism underlying a first case of HPV6-associated laryngeal carcinoma in juvenile-onset RRP, i.e. that HPV6 integration in the AKR1C3 gene resulted in loss of its expression. Alterations of AKR1C gene expression have previously been implicated in the tumorigenesis of other (HPV-related) malignancies.

Impediments to clinical diagnosis and management of juvenile-onset recurrent respiratory papillomatosis in Ilorin, Nigeria

Background: To report the impediments to the diagnosis and management of children with JuvenileOnset Recurrent Respiratory Papillomatosis as seen in a teaching hospital in West Africa. Methods: Retrospectively analysed study of participants requiring surgical intervention for histologically confirmed juvenile onset recurrent respiratory papillomatosis managed at the Department of Otorhinolaryngology, University of Ilorin Teaching Hospital, Ilorin over a 10-year period (2002-2011) using prospectively collated database. Results: Juvenile-Onset Recurrent Respiratory Papillomatosis constituted 8.8% of 307 laryngeal pathologies seen during the study period. 18 (66.7%) were males and 9 (33.3%) females with a sex ratio (M:F) of 2:1. Age ranged from 1 year 4 months to 12 years with a mean age of 6.1 years (SD = 2.78), with the 6 - 10 age group constituting the largest categories in 51.9% of patients seen. Patients from low socioeconomic class constituted slightly over half of the patients studied (51.9%). 55.5% of the patients presented late (>13 months). All patients presented with hoarseness, stridor and difficulty in breathing. Misdiagnosis made by the referring clinician included Asthma, Laryngo-tracheo-bronchitis, Foreign body aspiration and Laryngomalacia. Involvement of the glottis occurred in 70.4% of cases seen, while bilateral involvement was present in 91.3% of cases operated. Recurrence was seen in 63.0% of the patients and the best attendance at follow-up clinic was during the first three months post surgical extirpation. Emergency tracheostomy was done to relieve airway obstruction in 17 (63.0%) patients. Conclusion: Impediments to diagnosis and management of JORRP are multifactorial. Misdiagnosis, late presentation and poor follow-up clinic attendance of patients with JORRP is still a common occurrence among the physicians. Recommendations on how to improve management and outcome of JORRP were made.

Juvenile recurrent respiratory papilloma: Variable intersurgical intervals

To analyze the patterns of surgical frequency in pediatric patients undergoing surgery with CO(2) laser ablation for juvenile onset recurrent respiratory papillomatosis (JORRP). The hypothesis is that over time there is a high variability in surgical frequency independent of the use of an adjuvant therapy. Retrospective case review. All pediatric patients treated surgically with the CO(2) laser for JORRP by two senior surgeons at a tertiary pediatric hospital over an 11-year period were evaluated. Regression analysis was performed. An online survey was conducted of the American Academy of Pediatric Otolaryngology membership on their practice patterns regarding JORRP. Twenty-nine patients were identified, and of those, 20 were included in regression analysis. Several distinct patterns were noted. Only five of the 20 patients (25%) had a constant rate of procedures throughout the observation period. Three (15%) of the patients had continual decrease and one (5%) of the patients had a continual increase in the surgical rate throughout the study period. Eleven (55%) had a fluctuation in the pattern of their recurrences. When queried on how they approach when to repeat intervention for JORRP patients, more than 16 responses were given, and the most common determinants included standard set interval, previous operative findings, and previous interval. The natural fluctuation in intersurgical intervals without the use of any adjuvant therapy confounds the use of intersurgical interval as an outcome measure for the success of adjuvant therapy. Accelerations and decelerations were noted but cannot be explained.

Operative management of juvenile-onset recurrent respiratory papillomatosis

Juvenile-onset recurrent respiratory papillomatosis is a devastating illness of children who develop obstruction of the airway from neoplastic growths of infectious origin. The disease is caused by human papillomavirus (HPVs), types 6 and 11, incorporating itself into the genome of the respiratory mucosa. The consequence of this genetic piracy is a morphologic change from an airway lining that is flat and smooth to an irregular "mulberry like" hyperplasia. The growths seem to have a predilection for the glottic mucous membranes but can involve any part of the aerodigestive tract. The most common symptom is hoarseness, and children can have an alarming degree of obstruction with this as their only symptom. When hoarseness progresses to stridor, respiratory distress is impending. The dynamics of disease recurrence vary widely, with the more severe, rapidly recurring disease requiring frequent operative excisions to maintain airway patency. Surgery has been the mainstay of management but is not curative. Adjuvant therapies are elusively effective, unpredictably decreasing the disease activity and increasing the duration between surgeries. The quadrivalent HPV vaccine (Gardisil; Merck, NJ) is promising to reduce the HPV infection rate in young women, with the hope that by eliminating this reservoir of disease, the incidence of HPV-related illnesses, juvenile-onset including recurrent respiratory papillomatosis, will dramatically drop.

Molecular detection and incidence of human papillomavirus in neonates: Methodology and a pilot study in a medical center

Human papillomavirus (HPV) infection can cause laryngeal papillomas in children. Vertical transmission has been confirmed. This study aimed to establish a sensitive molecular diagnostic method and understand the incidence of the HPV-6 and HPV-11 in neonates with intubation. We enrolled 108 newborns between October 2007 and January 2010. All neonates were intubated due to underlying disease. The specimens were collected via endotracheal aspiration. DNA of HPV types 6 and 11 was detected by real-time PCR and nested PCR. HPV-DNA was detected in eight of the 108 newborns studied. Seven respiratory specimens tested positive for HPV-11 and one was positive for HPV-6. The HPV 6/11 detection rate in neonates was 7.4% (8/108). A rapid, sensitive, specific, and reproducible RT-PCR method and nest PCR were developed for the detection and differentiation of HPV-6 and HPV-11 genomic variants in a single PCR reaction. The assays are of great value for clinical and epidemiologic studies of HPV-6 and HPV-11 infections. Neonatal HPV colonization may be related to juvenile-onset recurrent respiratory papillomatosis. The transmission route may be from mother to child. The clinical significance of neonatal carriage of HPV-6 or HPV-11 warrants further study.

Remission in juvenile-onset recurrent respiratory papillomatosis

Background: Juvenile-onset recurrent respiratory papillomatosis (JORRP) is a distressing disease due to relentless recurrence and progression. In JORRP, recurrence is a rule, but remission can be considered if the disease-free period after a particular treatment modality is more than one year. Objective : The present study was undertaken with the aim to address this dilemma of remission in JORRP. Materials and Methods: A total of 30 patients of JORRP presenting over 2 years were included. Detailed history, aggressiveness of disease, number of surgical interventions, and surgical modality used were elicited. Videolaryngostroboscopy was performed in all patients using Kays RLS 9100B stroboscope. Papilloma excision was done using CO 2 laser and all patients were followed up three monthly for 1 year, then were kept on yearly follow-up. Results: It was observed that majority of the patients (83%) underwent recurrent excision of papillomas for 1 to 5 times. Of the 30 patients, 15 (50%) showed remission. Eleven of the 30 patients (36.67%) had minimal papillomas and symptomatic recurrence of papilloma was seen in four of the 30 patients (13.33%) and required further surgeries. Nine of the 30 patients who showed remission were diagnosed and managed within 1- to 15-year age group. Six of the 30 patients who presented with recurrence and minimal papillomas were in the age group 31 to 45 years. These patients had transition of JORRP to adult papilloma. Conclusion: The present study shows that the chance of remission is higher in children who had an early onset of JORRP. Remission was more when surgical excision was done only with CO2 laser.

Virological failure of intralesional cidofovir therapy in recurrent respiratory papillomatosis is not associated with genetic or epigenetic changes of HPV11: Complete genome comparison of sequential isolates

Five sequential human papillomavirus type 11 (HPV11) positive samples collected from an aggressive juvenile onset recurrent respiratory papillomatosis before, during and after intralesional cidofovir therapy leading to virological failure after initial response were analyzed. Sequencing of the complete genome as well as methylation analysis by bisulfate modification and sequencing of the long control region (LCR) were performed to seek for genetic and epigenetic changes as a possible background for therapy failure. Single-strand conformation polymorphism of E1, E2, E6, E7 and LCR was used to exclude the presence of multiple HPV11 infection. All five complete genomes were identical and all four E2 binding sites in the LCR were uniformly unmethylated in all five genomes. Thus the virological failure was not due to virological factors suggesting that cidofovir action may depend more heavily on the host.

The cost-effectiveness of male HPV vaccination in the United States

The objective of this study was to estimate the cost-effectiveness of adding human papillomavirus (HPV) vaccination of 12-year-old males to a female-only vaccination program for ages 12-26 years in the United States. We used a simplified model of HPV transmission to estimate the reduction in the health and economic burden of HPV-associated diseases in males and females as a result of HPV vaccination. Estimates of the incidence, cost-per-case, and quality-of-life impact of HPV-associated health outcomes were based on the literature. The HPV-associated outcomes included were: cervical intraepithelial neoplasia (CIN); genital warts; juvenile-onset recurrent respiratory papillomatosis (RRP); and cervical, vaginal, vulvar, anal, oropharyngeal, and penile cancers. The cost-effectiveness of male vaccination depended on vaccine coverage of females. When including all HPV-associated outcomes in the analysis, the incremental cost per quality-adjusted life year (QALY) gained by adding male vaccination to a female-only vaccination program was $23,600 in the lower female coverage scenario (20% coverage at age 12 years) and $184,300 in the higher female coverage scenario (75% coverage at age 12 years). The cost-effectiveness of male vaccination appeared less favorable when compared to a strategy of increased female vaccination coverage. For example, we found that increasing coverage of 12-year-old girls would be more cost-effective than adding male vaccination even if the increased female vaccination strategy incurred program costs of $350 per additional girl vaccinated. HPV vaccination of 12-year-old males might potentially be cost-effective, particularly if female HPV vaccination coverage is low and if all potential health benefits of HPV vaccination are included in the analysis. However, increasing female coverage could be a more efficient strategy than male vaccination for reducing the overall health burden of HPV in the population.

Papillomatose laryngée sévère évoluant vers un carcinome bronchopulmonaire associé à HPV 11 chez une enfant de 15 ans : à propos d’un cas

Malignant transformation of juvenile-onset recurrent respiratory papillomatosis (RRP) is a rare event and the cases reported have been mainly observed in adults. We report the case of a 15-year-old girl with a history of severe RRP who died of a HPV 11-associated bronchopulmonary squamous cell carcinoma with pericardial invasion. HPV 11 was identified in nasopharyngeal and tracheal papillomas, as well as in the pericardial fluid. HPV 11 isolate was further analyzed by amplification and sequencing of the E1, E2, E4, E6, and E7 genes. Only one amino acid substitution in E4 due to natural polymorphism was observed. Exons 5-9 of the patient's tumor protein 53 (TP53) gene were sequenced and no mutations were identified. This observation confirms that malignant conversion of juvenile-onset RRP associated with HPV 11 to squamous cell carcinoma may arise in children. HPV 11-induced carcinogenesis needs to be further investigated.