How Enhancing Immunity to Low-Risk HPV Could Cure Recurrent Respiratory Papillomatosis.
Ontology highlight
ABSTRACT:
SUBMITTER: Bai K
PROVIDER: S-EPMC8363585 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Human papillomavirus (HPV) types 6 and 11 can infect the squamous epithelium of the respiratory tract. Up to 8·9% of patients with HPV-associated recurrent respiratory papillomatosis (RRP) have pulmonary involvement. Pulmonary manifestations of HPV infection are associated with considerable morbidity, in part because treatment options and management guidelines are lacking. Patients with pulmonary RRP have a 32-times increased lifetime risk of malignant transformation compared with the overall RRP population. We review the clinical and radiographic presentation, pathological features, and genetics of pulmonary RRP, and we provide management algorithms based on our clinical experience with this complex patient population. In patients with suspected pulmonary involvement, tissue-sparing procedures to address growing lesions might be warranted given the chronicity and multifocality of the disease over a patient's lifetime. However, malignant transformation of pulmonary lesion(s) warrants standard-of-care treatment for primary lung squamous cell carcinoma. Large cohort studies are needed to understand the clinical course of pulmonary RRP and to identify molecular markers of increased risk of malignant transformation in order to develop guidelines for optimal and standardised surveillance and treatment.
| S-EPMC10634185 | biostudies-literature
Project description:In this cohort study we examined whether gender, age at onset, observation time or human papillomavirus (HPV) genotype are risk factors for an aggressive clinical course in Recurrent Respiratory Papillomatosis (RRP). Clinical data from patient records comprised gender, age at onset, date of first endolaryngeal procedure with biopsy, date of last follow-up, total number of endolaryngeal procedures, and complications during the observation period. Disease was defined as juvenile (JoRRP) or adult onset (AoRRP) according to whether the disease was acquired before or after the age of 18. Aggressive disease was defined as distal spread, tracheostomy, four surgical operations annually or >10 surgeries in total. DNA was extracted from formalin-fixed paraffin-embedded tissue. HPV genotyping was performed by quantitative PCR assay identifying 15 HPV genotypes. The study included 224 patients. The majority were males (141/174 in AoRRPs and 31/50 in JoRRPs; p = 0.005). The median follow-up from initial diagnosis was 12.0 years (IQR 3.7-32.9) for JoRRPs and 4.0 years (IQR 0.8-11.7) for AoRRPs. The disease was more aggressive in juveniles than adults (p<0.001), a difference that disappeared after 10 years' observation. JoRRPs with aggressive disease were younger at onset (mean difference 4.6 years, 95%CI [2.4, 6.8], p = 0.009). HPV6 or -11 was present in all HPV-positive papillomas. HPV11 was more prevalent in aggressive disease, and HPV6 in non-aggressive disease (p<0.001). Multiple logistic regression revealed that only age at onset (OR = 0.69, 95% CI [0.53, 0.88], p = 0.003) was associated with aggressive disease in juveniles, while HPV11 (OR = 3.74, 95% CI [1.40, 9.97], p = 0.008) and observation time >10 years (OR = 13.41, 95% CI [5.46, 32.99[, p<001) were risk factors in adults. In conclusion, the only significant risk factor for developing aggressive disease in JoRRPs was age at onset, but both HPV11 and observation time >10 years were risk factors for an aggressive disease course in AoRRPs.
| S-EPMC4242649 | biostudies-other
Project description:ObjectiveDespite recent advancement recurrent respiratory papillomatosis (RRP) remains a rare but challenging benign airway neoplasm. In recent years there has been significant shifts in incidence of this disease due to changes in vaccination and prevention for human papilloma virus (HPV) and its related pathology. This review will highlight the epidemiology, prevention and treatment of RRP.MethodsThe PubMed database was searched using relevant MeSH terms including "recurrent respiratory papillomatosis." The titles and abstracts were reviewed to assess relevance and unrelated articles were excluded. A full-text review for select articles was performed, the data and discussions were interpreted and synthesized to create a concise update on the management of RRP.ResultsWith the increasing utilization of the 9-valent and quadrivalent HPV vaccine in Australia, we have seen a significant decrease in the incidence of RRP. Preliminary data in the US shows a similar trend of decreased incidence after implementation of vaccination. Single dose Gardasil in developing countries has shown sustained immunization for at least 7 years. Preliminary clinical trials and retrospective studies have shown the HPV vaccine may have benefit as a treatment method in addition to prevention for HPV related diseases. Bevacizumab (Avastin), a VEGF monoclonal antibody, has shown promise as a systemic treatment for RRP. The Corona Virus Disease 2019 (COVID-19) pandemic has affected perioperative management of RRP.ConclusionRRP continues to decline in incidence since the implementation of HPV vaccination. Advancement in the medical management including Bevacizumab show promise as an additional option for the management of RRP.
| S-EPMC8035938 | biostudies-literature
Project description:Recurrent respiratory papillomatosis (RRP) is a rare disease caused by human papillomavirus. Aggressive forms of RRP require repeated cytoreductive surgery to restore airway patency. Tracheal disease is even less common and lung parenchyma is involved in less than 1% of patients. We present reports of three cases of RRP with progressive lung disease in adult patients.
| S-EPMC6214881 | biostudies-literature
Project description:The micromilieu within respiratory papillomas supports persistent human papillomavirus (HPV) infection and disease recurrence in patients with recurrent respiratory papillomatosis (RRP). These patients show polarized (TH2-/Treg) adaptive immunity in papillomas and blood, enriched immature Langerhans cell (iLC) numbers, and overexpression of cyclooxygenase-2/prostaglandin E2 (PGE2) in the upper airway. Blood monocyte-derived, and tissue-derived iLCs from RRP patients and controls were now studied to more fully understand innate immune dysregulation in RRP. Patients' monocytes generated fewer iLCs than controls, due to a reduced fraction of classical monocytes that generated most but not all the iLCs. Prostaglandin E2, which was elevated in RRP plasma, reduced monocyte-iLC differentiation from controls to the levels of RRP patients, but had no effect on subsequent iLC maturation. Cytokine/chemokine responses by iLCs from papillomas, foreskin, and abdominal skin differed significantly. Freshly derived tissue iLCs expressed low CCL-1 and high CCL-20 mRNAs and were unresponsive to IL-36γ stimulation. Papilloma iLCs uniquely expressed IL-36γ at baseline and expressed CCL1 when cultured overnight outside their immunosuppressive microenvironment without additional stimulation. We conclude that monocyte/iLC innate immunity is impaired in RRP, in part due to increased PGE2 exposure in vivo. The immunosuppressive papilloma microenvironment likely alters iLC responses, and vice versa, supporting TH2-like/Treg HPV-specific adaptive immunity in RRP.
| S-EPMC7076114 | biostudies-literature
Project description:IntroductionHuman papillomavirus (HPV) causes juvenile-onset recurrent respiratory papillomatosis (JORRP). Although HPV is common in children, the prevalence of JORRP is low. It is likely that other factors contribute to the pathogenesis of JORRP, during either activation or reactivation of a latent HPV infection. There is evidence that laryngopharyngeal reflux (LPR) might be such a risk factor for adult-onset recurrent respiratory papillomatosis. This study investigated if LPR might also be a risk factor for JORRP.Materials and methodsChildren with JORRP of the larynx that required microlaryngoscopy at a tertiary referral hospital were included in this prospective case-series study from November 2015 to November 2017. Using immunohistochemistry, HPV infection and pepsin associated with LPR were diagnosed from laryngeal biopsies.ResultsEleven children (aged 4-14 years) were analyzed. No patient had a history of immunodeficiency or tobacco smoke exposure. All patients underwent at least three previous surgeries due to JORRP and had been vaccinated against HPV in the past. Five children were treated using antivirotics and immunomodulators. The only known maternal risk factor was that three mothers were primiparous. All 11 samples were infected with HPV (type 6 or 11). Pathologic LPR was diagnosed in 5/11 children (45.5%).ConclusionLPR may be a risk factor for JORRP, contributing to its development by activating or reactivating a latent HPV infection. Results are in accordance with those from our previous study in adults.
| S-EPMC6387692 | biostudies-literature
Project description:ObjectivesRecurrent respiratory papillomatosis (RRP) is a chronic disease of the respiratory tract that occurs in both children and adults. It is caused by the human papillomavirus (HPV), in particular low-risk HPV6 and HPV11, and aggressiveness varies among patients. RRP remains a chronic disease that is difficult to manage. This review provides perspectives on current and future management of RRP.ResultsThe current standard of care is surgical excision, with adjuvant therapies as needed. Surgical management of RRP has evolved with the introduction of microdebriders and photoangiolytic lasers; the latter can now be used in the office setting. Numerous adjuvant pharmacologic therapies have been utilized with some success. Also, exciting preliminary data show that HPV vaccines may prolong the time to recurrence in the RRP population. There is also optimism that wide-spread HPV vaccination could reduce RRP incidence indirectly by preventing vertical HPV transmission to newborns.ConclusionTo date, the biology of RRP is not well understood, although it has been noted to become more aggressive in the setting of immune suppression. Additional research is needed to better understand immune system dysfunction in RRP such that immunomodulatory approaches may be developed for RRP management.Level of evidence4.
| S-EPMC5824106 | biostudies-literature
Project description:Recurrent respiratory papillomatosis (RRP) is characterised by multiple laryngeal papillomas. Left untreated, the lesions enlarge, spread, and endanger the airway. Medical treatments are unsatisfactory, and repeated surgery remains the mainstay of therapy. RRP is caused by human papillomavirus (HPV) infection. However, since oral HPV infection is common and RRP is rare, other host and/or viral factors may contribute to pathogenesis. In an attempt to identify such factors, we have investigated 60 patients. The patients were HLA class I, II, and tumor necrosis factor TNF typed by sequence-specific primer PCR, and the results compared to those for 554 healthy controls by using Fisher's exact test. Peripheral blood mononuclear cell proliferative responses of 25 controls and 10 patients to HPV-11 L1 virus-like particles (VLP) were compared. Short-term VLP-specific T-cell lines were established, and recognition of L1 was analyzed. Finally, the L1 open reading frames of HPV isolates from four patients were sequenced. Susceptibility to RRP was associated with HLA DRB1*0301 (33 of 60 patients versus 136 of 554 controls, P < 0.0001). The three most severely affected patients were homozygous for this allele. A range of T-cell proliferative responses to HPV-11 VLP were observed in DRB1*0301-positive healthy donors which were comparable to those in DRB1*0301-negative controls. Individuals with juvenile-onset RRP also mounted a range of VLP responses, and their magnitude was negatively correlated with the clinical staging score (P = 0.012 by the Spearman rank correlation). DRB1*0301-positive patients who responded to L1 recognized the same epitope as did matched controls and produced similar cytokines. Sequencing of clinical isolates excluded the possibility that nonresponsiveness was the result of mutation(s) in L1.
| S-EPMC140867 | biostudies-literature
Project description:ObjectiveRecurrent respiratory papillomatosis (RRP) is a rare disease for which a limited number of information sources for patients exist. The role of the Internet in the patient-physician relationship is increasing. More and more patients search for online health information, which should be of good quality and easy readable. The study aim was to investigate the quality and readability of English online health information about RRP.Study designQuality and readability assessment of online information.MethodsRelevant information was collected using three different search engines and seven different search terms. Quality was assessed with the DISCERN instrument. The Flesch Reading Ease Score (FRES) and average grade level (AGL) were determined to measure readability of the English websites.ResultsFifty-one English websites were included. The mean DISCERN score of the websites is 28.1 ± 9.7 (poor quality); the mean FRES is 41.3 ± 14.9 (difficult to read); and the mean AGL is 12.6 ± 2.3.ConclusionThe quality and readability of English websites about RRP is alarmingly poor.Level of evidenceNA. Laryngoscope, 127:2293-2297, 2017.
| S-EPMC5638064 | biostudies-literature
Project description:Activation of antigen-specific T-lymphocyte responses may be needed to cure disorders caused by chronic infection with low-risk human papillomavirus (lrHPV). Safe and effective adjuvant therapies for such disorders are needed. The safety and efficacy of a novel gorilla adenovirus vaccine expressing a protein designed to elicit immune responses directed against HPV6 and HPV11, PRGN-2012, was studied using in vitro stimulation of T lymphocytes from patients with recurrent respiratory papillomatosis, in vivo vaccination studies, and therapeutic studies in mice bearing tumors expressing lrHPV antigen. PRGN-2012 treatment induces lrHPV antigen-specific responses in patient T lymphocytes. Vaccination of wild-type mice induces E6-specific T-lymphocyte responses without toxicity. In vivo therapeutic vaccination of mice bearing established HPV6 E6 expressing tumors results in HPV6 E6-specific CD8+ T-lymphocyte immunity of sufficient magnitude to induce tumor growth delay. The clinical study of PRGN-2012 in patients with disorders caused by chronic infection with lrHPV is warranted.
| S-EPMC8213691 | biostudies-literature