Juvenile Respiratory Papillomatosis Research Articles

Vaccination against human papillomavirus in aggressive juvenile respiratory papillomatosis

In recent years there has been an increase in cases of papillomatosis of the upper respiratory tract, including in childhood, which is a significant problem. More than 70 % of children have severe recurrent forms of the disease. It has been proven that the development of respiratory papillomatosis is associated with infection with human papillomavirus, more often HPV types 6 and 11. The development of respiratory papillomatosis in childhood may be a consequence of infection with the human papillomavirus of the respiratory tract at the time of birth, and HPV reactivation may occur after injury or infection. The treatment of this condition is a significant problem, since during surgical treatment, only the visible pathological process is excised, and no effect on the etiological factor is produced. Therefore, the most optimal can be considered to be vaccination against HPV with available vaccines at the stage of pregnancy planning in previously unvaccinated individuals, as well as vaccination against HPV in already infected individuals with existing respiratory papillomatosis. In our article, we present a case of successful vaccination of a 2-year-old child with an aggressive course of respiratory papillomatosis against HPV.

A Patient with Juvenile Recurrent Respiratory Papillomatosis Complicated by Laryngeal Stenosis after Laryngeal Microsurgery: A Clinical Case

BACKGROUND: The relevance of the problem of juvenile respiratory papillomatosis lies in the recurrent course of the disease in young children. This can lead to the development of respiratory stenosis, requiring repeated, in some cases, monthly surgical treatments for endolaryngeal removal of papillomas, which sometimes leads to persistent scar stenosis of the larynx. We present clinical case of achieving remission of recurrent juvenile papillomatosis of the larynx. CLINICAL CASE: Patient, 5 years old, who applied in February 2016, was hospitalized in the ENT department with severe dyspnea, laryngoscopy revealed laryngeal papillomatosis with 3–4 grade stenosis. Over the past 10 months, the patient has undergone laryngeal surgery 6 times using cold instruments and a CO2 laser due to papillomatosis. Taking into account the recurrent nature of the course of the disease, the patient is administered to consult an allergist-immunologist. Based on the anamnesis and the results of the tests, the immunologist-allergist diagnosed: Primary immunodeficiency, unspecified (insufficiency in the production of specific antibodies), persistent allergic rhinitis, in the stage of incomplete remission and prescribed treatment. The patient was operated twice from 2017 to 2018 for a developed post-operative complication – cicatricial stenosis of the larynx. With these surgical repairs, no recurrence of laryngeal papillomatosis was detected. Furthermore, in 2021, according to endovideolaryngoscopy, remission was confirmed. R In this clinical case, we managed to achieve remission of laryngeal papillomatosis in a patient after surgery and treatment by an immunologist. Allergen elimination and immunocorrection helped us achieve deep remission. Surgical treatment eliminated laryngeal stenosis, recovering breathing and voice quality. Furthermore, this clinical case demonstrates the importance of studying the immune status in patients with laryngeal papillomatosis. CONCLUSION: The results obtained by us show the need for the use of immunomodulators in these patients. All children with prolonged hoarseness should undergo laryngoscopy, which will allow diagnosing laryngeal papillomatosis at earlier uncomplicated stages of the disease. Treatment of laryngeal papillomatosis should be comprehensive and in addition to surgical treatment should include differential immune correction. RESULTS AND DISCUSSION: In the above clinical case, we managed to achieve remission of laryngeal papillomatosis in a patient after surgery and treatment by an immunologist. Allergen elimination and immunocorrection helped us achieve deep remission. Surgical treatment eliminated laryngeal stenosis, recovering breathing and voice quality. Furthermore, this clinical case demonstrates the importance of studying the immune status in patients with laryngeal papillomatosis. The results obtained by us show the need for the use of immunomodulators in these patients. All children with prolonged hoarseness should undergo laryngoscopy, which will allow diagnosing laryngeal papillomatosis at earlier uncomplicated stages of the disease. Treatment of laryngeal papillomatosis should be comprehensive and in addition to surgical treatment should include differential immune correction.

Hypercalcemia with invasive pulmonary papillomatosis and microinvasive squamous carcinoma

Juvenile respiratory papillomatosis is a rare pediatric disease in which benign papillomata develop in the respiratory tract, most commonly involving the larynx and tracheobronchial tree. Invasive pulmonary papillomatosis is an aggressive form in which the papillomata extend into the lung parenchyma. We report a case of a 22-year-old man with a long-standing juvenile respiratory tract papillomatosis, initially diagnosed at age 2, who subsequently developed invasive pulmonary papillomatosis and underwent partial surgical resection for his pulmonary disease. Hypercalcemia complicated the patient’s final hospitalizations. HPV typing performed on a laryngeal papilloma was positive for HPV 6/11. The lobectomy specimen revealed malignant transformation of invasive pulmonary papillomatosis characterized by the presence of microinvasive nests of squamous carcinoma. Immunohistochemical stain for parathyroid hormone on the invasive component was negative. Eventually, the patient succumbed to his disease and while the family refused post-mortem examination, Positron Emission Tomography (PET) performed during the patient’s terminal course suggested the possibility of metastasis to liver and periaortic lymph nodes. There was no evidence of bony metastasis.

Immunological aspects of the juvenile respiratory papillomatosis of the larynx

Immunological aspects of the juvenile respiratory papillomatosis of the larynx

Efficacy of cidofovir in recurrent juvenile respiratory papillomatosis

The efficacy of cidofovir in juvenile recurrent respiratory papillomatosis (JRRP) remains uncertain due to the lack of published case-control studies.AimTo establish factors affecting the progression of JRRP prognosis, and to evaluate cidofovir for eradicating JRRP.Study designRetrospective.Methods22 children with JRRP were evaluated at a referral center. All children underwent surgical debulking, followed by cidofovir injection (Group 2) or not (Group 1). Age at diagnosis was correlated with the Derkay score and disease outcome. Disease progression was compared between groups 1 and 2.Resultsfifteen children were considered disease-free; 8 were in Group 2 and 7 in Group 1. Age and total and clinical scores (P<0.05) were negatively correlated. The mean number of surgeries required to control the disease was identical in both groups; the duration of treatment until remission was significantly higher in Group 1 (P<0,05).ConclusionJRRP is more aggressive in earlier onset disease. The duration of treatment was significantly lower in patients treated with cidofovir until eradication of JRRP compared to patients treated with surgery only.

The role of the perinatal transmission and persistence of human papilloma virus in the development of juvenile respiratory papillomatosis

This review paper presents the results of the recent studies designed to elucidate the etiopathogenetic role ofhuman papilloma virus infection in the development of respiratory papillomatosis in the children. Special attention is given to the possible pathways and mechanisms of the mother-to-child transmission of papilloma virus, its frequency and risk factors during pregnancy and in the postnatal period. The results of investigations into the frequency of papilloma virus infection in the children are presented along withrisk factors contributing to its persistence and the development ofjuvenile respiratory papillomatosis. The possible approaches to the management of this condition are proposed.

Juvenile respiratory papillomatosis: Risk factors for severity

Juvenile recurrent respiratory papillomatosis is caused mainly by human papillomavirus genotypes 6 or 11, acquired at birth or during pregnancy from an infected mother. Recurrent respiratory papillomatosis is characterized by recurring warts growing most commonly in the larynx. Multiple surgical procedures and the risk of airway obstruction contribute to the devastating impact of this disease. Some children will go into remission after a few surgeries whereas others will require repeated interventions over several years. Further understanding of the risk factors associated with severity may contribute to tailored treatments. A retrospective study of cases diagnosed between January 1995 and December 2008 was conducted to study determinants of severe forms of juvenile recurrent respiratory papillomatosis. Demographic and clinical variables were abstracted from children's medical charts and mothers' delivery charts. Viral factors (HPV genotyping and viral load) were studied from archived biopsies. Specific HLA class II alleles and killer-cell immunoglobulin-like receptors genes were tested from saliva samples. Logistic regression was performed to identify risk factors for severity. Overall, 31 pediatric cases of recurrent respiratory papillomatosis were identified. The only significant factor associated with severe forms of recurrent respiratory papillomatosis was the maternal history of condylomas during pregnancy (OR: 12.05 [P=0.05]). The analysis failed to identify risk factors that could be used clinically to identify recurrent respiratory papillomatosis cases likely to take a severe course. Although too early to determine, vaccination against the HPV types involved most commonly in recurrent respiratory papillomatosis may provide the best hope to prevent severe forms of this disease.

The spectrum and clinical sequelae of human papillomavirus infection

Infection with the human papillomavirus (HPV) is the most common sexually transmitted disease afflicting approximately 80% of the population. HPV infection is an essential factor in cervical carcinogenesis and cervical carcinoma is the second most common cause of cancer among women worldwide. In addition to cervical cancer, other malignancies in both men and women such as esophageal, oropharyngeal, and anal cancer have been causally associated with this virus. Other gender-specific HPV-related cancers include penile, vulvar and vaginal cancer. HPV-16 is the most common HPV type associated with a malignant phenotype regardless of organ of origin. HPV-16 together with HPV-18 accounts for approximately 70% of cervical cancers. Other non-oncogenic HPV types including HPV types 6 and 11 are associated with over 90% of benign HPV-related lesions such as genital warts and juvenile respiratory papillomatosis.

Preliminary report of endolaryngeal and endotracheal laser surgery of juvenile-onset recurrent respiratory papillomatosis by Nd:YAG laser and a new fiber guidance instrument

Objectives Recurrent respiratory papillomatosis (RRP) caused by human papilloma virus (type 6 and 11) is the most common benign neoplasm of the larynx in children. Despite being a benign disease, treatment is very difficult and is characterized by frequent recurrence, spread throughout the respiratory tract, and malignant degeneration. Besides surgical resection and the established CO 2 laser treatment, laser surgery by fiber-guided Nd:YAG laser light promises to be a bloodless and effective treatment procedure. To improve this new method, a novel fiber guidance instrument has been developed to aid in endolaryneal laser surgery of RRP. Study design and setting The method described uses a specially designed instrument for fiber guidance that is equipped with a bendable distal tip to move the fiber end precisely. Moreover, the instrument includes an additional channel for the suction of smoke and pyrolysis products. Up to now, 5 patients (aged 4 to 8 years) with RRP were treated by Nd:YAG laser light (λ = 1064 nm; power, 10W; irradiance, 3.5 kW/cm 2, continuous wave) with a prototype version of the new instrument and were followed up for 12 months each. Results Because of the adequate length and the bendable distal tip with a range of –5° up to 45° to the optical axis of the fiber and less than 10% light loss at maximal deflection, RRP can be treated by Nd:YAG laser light easily and precisely. The continuous suctioning ensured an optimum view of the operating field and a minimal load of potential infectious laser plume and toxic pyrolysis products for the patient as well as for the physician. The laser treatment of RRP with the new fiber guidance instrument was only minimally traumatic. During 1-year follow-up visits, all Nd:YAG laser light-treated patients, showed a regression of the disease. Conclusions The new fiber guidance instrument enables a precise and easy treatment of the RRP with fiber-guided laser systems (eg, Nd:YAG-, diode-, and KTP-lasers) and an effective removal of infectious laser plume as well as toxic pyrolysis products. A follow-up period of 1 year revealed that Nd:YAG laser surgery seems to prevent a rapid recurrence of juvenile respiratory papillomatosis in the treated patients.

Topoisomerase Alpha II, Retinoblastoma Gene Product, and p53: Potential Relationships With Aggressive Behavior and Malignant Transformation in Recurrent Respiratory Papillomatosis

Recurrent respiratory papillomatosis (RRP) has a juvenile aggressive form and an adult more indolent form. Most cases of RRP are cytologically benign; however, some undergo malignant transformation. At present, there are no known markers that help identify patients at risk for aggressive disease. We investigated by immunohistochemistry expressions of topoisomerase alpha II, MIB-1, p53, p21, E-cadherin, retinoblastoma (RB) gene protein product, HER-2/neu, and steroid hormone receptors in a case of juvenile respiratory papillomatosis with malignant transformation to determine whether these markers are associated with malignant transformation. Histologic examination of the pulmonary lobectomy specimen revealed well-differentiated squamous carcinoma and invasive papillomatosis. Increased staining was found in areas of invasive papillomatosis for topoisomerase alpha II, p53, and MIB-1, with highest labeling indices in areas of squamous carcinoma. Staining intensity for RB gene protein product showed gradual decline from benign papilloma (3+) and invasive papillomatosis (2+) to squamous carcinoma (0-1+). Expression of p21 was similar in benign papilloma and invasive papillomatosis but showed reduction in squamous carcinoma. Expressions of E-cadherin, HER-2/neu, and steroid hormone receptors did not appear to correlate with biologic behavior. Increased topoisomerase alpha II and p53 expression along with reduced RB gene protein product and p21 expression may serve as markers of transformation to invasive papillomatosis and squamous carcinoma.

Expression of Ki-67, tumor suppressor proteins, growth factor, and growth factor receptor in juvenile respiratory papillomatosis: Ki-67 and p53 as predictors of aggressive disease

The enhanced proliferation of epithelial cells is a typical feature of respiratory papilloma. The mechanism or mechanisms leading to abnormal epithelial proliferation remain unclear. Overexpression of growth factors and their receptors and inactivation of tumor-suppressor proteins are known to cause cell transformation and proliferation. The objectives of this study were to evaluate the expression of these factors in juvenile respiratory papillomas with correlation to cellular proliferation activity, and to determine whether such expression is associated with the clinical course of the disease. The expression of transforming growth factor-α, epidermal growth factor receptor, p53 protein, retinoblastoma proteins and Ki-67 was quantified by immunohistochemistry in paraffin-embedded biopsy specimens taken at the initial surgical excision from children in whom respiratory papillomatosis was diagnosed. Clinical information regarding the number of disease sites, tracheobronchial spread, malignant transformation, and frequency of recurrences was reviewed. Thirty-five specimens were suitable for immunohistochemical evaluation. Ki-67 expression was significantly higher in patients with multiple sites of disease and frequent recurrences. High p53 expression was significantly associated with malignant transformation. We concluded that Ki-67 and p53 expression may be predictive of the clinical course in children with respiratory papillomatosis. (Otolaryngol Head Neck Surg 2000;122:378-86.)

High risk genital papillomavirus infections are not spread vertically

The Medline-indexed literature on risk factors for HPV infection and HPV transmission is critically reviewed. Principles for assay validation and interpretation, reliability of different study designs and principles for interpretation of conflicting reports are discussed. The conclusions arrived at can be summarised as: (1) There is overwhelming epidemiological evidence that the only quantitatively important mode of transmission of infection with oncogenic genital HPV types is sexual. (2) There is also evidence that benign genital HPV types can be transmitted sexually, but the epidemiological data on the benign virus types are less extensive and less clear. (3) Perinatal HPV transmission is unequivocally demonstrated only for the rare disease juvenile respiratory papillomatosis. Copyright © 1999 John Wiley & Sons, Ltd.

High risk genital papillomavirus infections are not spread vertically.

The Medline-indexed literature on risk factors for HPV infection and HPV transmission is critically reviewed. Principles for assay validation and interpretation, reliability of different study designs and principles for interpretation of conflicting reports are discussed. The conclusions arrived at can be summarised as: (1) There is overwhelming epidemiological evidence that the only quantitatively important mode of transmission of infection with oncogenic genital HPV types is sexual. (2) There is also evidence that benign genital HPV types can be transmitted sexually, but the epidemiological data on the benign virus types are less extensive and less clear. (3) Perinatal HPV transmission is unequivocally demonstrated only for the rare disease juvenile respiratory papillomatosis.

Significance of DNA ploidy and cell proliferation in juvenile respiratory papillomatosis.

The clinical course of recurrent respiratory papillomatosis (RRP) in children is variable and unpredictable. At present there is no way to identify patients at risk for aggressive disease. The objective of this study was to evaluate whether DNA ploidy and cell proliferation analyses can predict the clinical course in children with RRP. Two different methods of estimating proliferation activity were compared. Nonembedded papilloma biopsy specimens from 18 pediatric patients were analyzed by flow cytometry providing DNA content with cell cycle analysis. The expression of the proliferative marker Ki-67 in papilloma tissue was quantified by immunohistochemistry. The patients were prospectively observed for 12 to 18 months. DNA content analysis and Ki-67 expression were compared to clinical information regarding number of disease sites, distal tracheobronchial spread, number of recurrences, need for tracheostomy, and disease remission. High S-phase fraction, proliferative index, and Ki-67 expression correlated with an aggressive clinical course. DNA ploidy analysis and immunodetection of proliferative markers may assist in predicting prognosis in children with RRP.

S-phase fraction as a predictor of prognosis in juvenile respiratory papillomatosis.

To determine whether DNA ploidy and the S-phase fraction are predictive of the clinical course in children with recurrent respiratory papillomatosis. Masked compression of DNA analysis findings to the clinical course of the disease. Tertiary referral center. All pediatric patients treated for recurrent respiratory papillomatosis at our institution between 1989 and 1995 who had adequate follow-up and whose primary biopsy specimen was available for examination. Fifty-five patients met these criteria. Information was collected from the case notes on the patient's age at presentation, sex, sites of disease, duration of active disease, and frequency of operative interventions. Flow cytometric analysis was performed on the archival paraffin-embedded primary biopsy specimen obtained at the initial surgical excision, providing DNA content and percentages of S-phase cells. The investigators who performed the DNA analysis were masked to the clinical course. The age of the patients at presentation ranged from 3 months to 16 years. Thirty patients had involvement in more than 1 anatomical site. The disease in 10 patients had spread to the distal tracheobronchial tree. The patients underwent a total of 1124 procedures, with a frequency range of 7 to 27 per year. All cell populations studied were diploid. The percentage of S-phase cells was significantly higher in the primary biopsy specimen from patients with disease characterized by more frequent recurrences, multiple sites, and distal extension (P<.05). In multiple regression analysis, the S-phase fraction was found to be an independent and powerful prognostic factor for aggressive disease. The S-phase fraction may be predictive of the clinical course in patients with juvenile respiratory papillomatosis. Prospective studies are needed to assess the diagnostic and clinical value of our primary results and to determine whether DNA analysis can assist in identifying patients at increased risk for an aggressive clinical course.

Expressions of Ki67, Tumor Suppressor Proteins, Growth Factors and Their Receptors in Juvenile Respiratory Papillomatosis: Ki67 and p53 as Predictors of Aggressive Disease

Expressions of Ki67, Tumor Suppressor Proteins, Growth Factors and Their Receptors in Juvenile Respiratory Papillomatosis: Ki67 and p53 as Predictors of Aggressive Disease

Expressions of Ki67, tumor suppressor proteins, growth factors and their receptors in juvenile respiratory papillomatosis: Ki67 and p53 as predictors of aggressive disease

Expressions of Ki67, tumor suppressor proteins, growth factors and their receptors in juvenile respiratory papillomatosis: Ki67 and p53 as predictors of aggressive disease

Ribavirin treatment for juvenile respiratory papillomatosis

Juvenile respiratory papillomatosis involving the tracheo-bronchial tree imposes a significant management problem and is sometimes life threatening. The mainstay of treatment is repeated vapourization with a CO2 laser. To date, adjunctive medical treatments have been of limited value. A tracheostomized child with extensive laryngo-tracheo-bronchial papillomatosis who has required bronchoscopic lasering at two-weekly intervals for three years was treated with ribavirin, a broad spectrum anti-viral agent. The drug was administered in nebulized form using a small particle aerosol generator (S.P.A.G.) to the lower respiratory tract (6 gm/150 ml over nine hours) on three consecutive nights every two weeks over seven weeks and also administered orally (15 mg/kg/day). Endoscopic assessments were made every two weeks. At 14 days the papillomata were regressing and far less lasering was required. No further lasering was required up to 56 days. One month after stopping the ribavirin, however, a few sessile papillomata in the tracheo-bronchial tree had recurred and were treated with the laser. No adverse reactions were encountered. During the treatment period there was a significant reduction in the frequency of therapeutic endoscopies. This promising response requires further evaluation to define the role of ribavirin in the treatment of juvenile respiratory papillomatosis.

Juvenile respiratory papillomatosis: acyclovir reassessed

Four patients with aggressive respiratory papillomatosis have been treated with oral Acyclovir as adjuvant therapy while continuing to undergo regular endoscopy and laser treatment to the lesions. The duration of Acyclovir administration ranged from 2 weeks to 3 months. Two patients had papillomatosis confined to the larynx and two in addition had disease in the lower respiratory tract. One of the four patients had less aggressive disease during the treatment period. Acyclovir does not appear to significantly influence respiratory papillomatosis. Acyclovir's activity is dependent upon the presence of virally encoded thymidine kinase. This enzyme is not known to be encoded by papilloma viruses. Acyclovir is not recommended in the treatment of juvenile respiratory papillomatosis.