Human papilloma virus in the etiopathogenesis of allergic nasal polyposis: A prospective study.

PURPOSE: To evaluate and compare the prevalence of high-risk HPV and low-risk HPV types in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) and healthy controls. MATERIALS AND METHODS: A prospective cohort study was conducted in a tertiary care hospital on the patients of CRSwNP undergoing surgical management. All patients underwent preoperative endoscopic evaluation and radiological assessment using NCCT of the nose and paranasal sinuses. The severity of the disease was graded using the Lund-Mackay score on NCCT. All patients underwent endoscopic polypectomy and the sample of tissues was sent for HPV DNA detection using Hybrid Capture II® technique. The clinicopathological characteristics of HPV positive and negative patients were compared. RESULTS: Sixty cases and 20 controls were included in the study. All controls were negative for HPV DNA. 27 patients (45%) had the presence of HPV DNA, out of which 23 had only LR-HPV and 1 had only HR-HPV types. Three patients had both HR-HPV and LR-HPV subtypes. There was a significant difference between the cases and controls for the presence of HPV DNA (p < 0.001). However, the patients with HPV-positive DNA in the nasal specimen did not differ significantly from HPV-negative patients in age, gender, or severity of the disease. CONCLUSIONS: Human papillomaviruses may play a significant role in the etiopathogenesis of CRSwNP, however, do not impact the degree of sinus involvement.

Squamous Cell Carcinoma In Situ Originating From Nasal Polyps With Human Papillomavirus 51 Infection: A Case Report.

Malignant transformation of nasal polyps is extremely rare in cases without background inverted papilloma. Human papillomavirus (HPV) is a sexually transmitted infection believed to be associated with oropharyngeal carcinoma via oro-genital sexual contact. We present a case of focal squamous cell carcinoma in situ that occurred on the surface of nasal polyps and was associated with HPV 51. The patient was successfully treated with endoscopic sinus surgery. Clinicians should be aware of the potential for hidden malignancies, and pathologic assessment of tissue specimens must be performed even in simple nasal polyp cases.

Investigation of Human Papillomavirus (HPV) and Epstein-Barr Virus (EBV) in antrochoanal polyps.

OBJECTIVES/HYPOTHESES: This study aimed to investigate the presence of HPV (HPV types 11 and 16) and EBV in antrochoanal polyps and to contribute to the current literature in this regard. STUDY DESIGN: A case-control study. METHODS: A total of 100 patients (including 43 patients undergoing surgery for antrochoanal polyp, 27 patients undergoing surgery for nasal polyp, and 30 patients undergoing surgery for hypertrophic inferior turbinate) were included in this study. DNA was isolated from formalin-fixed, paraffin-embedded samples with the aid of the Bioneer's AccuPrep Genomic DNA Extraction Kit. In the obtained genomic DNAs, while the detection of HPV DNA was performed using the nested-PCR method, the detection of HPV types 11/16 and EBV DNA was performed using the RT-PCR method. RESULTS: The mean age of the patients with antrochoanal polyp was 26.7 ±â€¯15.4 years (range 7-70). There were 20 (46.5%) women and 23 (53.5%) men in the antrochoanal polyp group. HPV DNA was positively detected using the nested-PCR method in 14 (32.6%) of the patients with antrochoanal polyp and in 3 (11.1%) of the patients with nasal polyp. HPV DNA was not detected in the hypertrophic inferior turbinate group (control group). There was a statistically significant difference between all groups in terms of HPV DNA positivity. In the antrochoanal polyp group, 2 patients had HPV 11 positivity and 12 patients had HPV 16 positivity. In the nasal polyp group, 1 patient had HPV 11 positivity and 2 patients had HPV 16 positivity. EBV DNA was positively detected in 16 (37.2%) of the patients with antrochoanal polyp, in 11 (40.7%) of the patients with nasal polyp and in 8 (26.7%) of the patients with hypertrophic inferior turbinate, respectively. There was no statistically significant difference between the groups in terms of EBV DNA positivity. CONCLUSIONS: This study demonstrates that there is a need for further studies investigating the presence of viruses in antrochoanal polyps.

H3N2 influenza virus infection enhances oncostatin M expression in human nasal epithelium.

Tight junctions (TJs) alteration is commonly seen in airway inflammatory diseases. Oncostatin M (OSM) is an inflammatory mediator associated with chronic rhinosinusitis with nasal polyps (CRSwNP). We have previously shown that human nasal epithelial cells (hNECs) are highly permissive cells for influenza A virus (IAV). However, its role in TJs alteration and the effects of IAV on inducing OSM expression in nasal epithelium remains to be further investigated. In this study, OSM and TJs expression was measured and compared between inferior turbinate from healthy controls and nasal polyps from CRSwNP. Additionally, hNECs cultured at air-liquid interface (ALI) were infected with H3N2 influenza virus to study the role of influenza virus in inducing epithelial OSM expression as a possible means of exacerbation. The expression of ZO-1, claudin-1, and occludin was markedly decreased and correlated negatively with that of OSM in CRSwNP. By using the in vitro hNEC model, H3N2 infection resulted in significantly increased OSM expression (2.2-, 4.7- and 3.9-fold higher at 8, 24, and 48 h post-infection vs. mock infection). Furthermore, OSM is found to co-localize with ciliated and goblet cells in hNECs infected with H3N2 influenza virus. Our findings demonstrated that increased OSM expression is implicated in CRSwNP as a possible mechanism of TJs' impairment, which can be further augmented following influenza infection via epithelial OSM expression, possibly contributing to exacerbations.

[The relationship between viral infection and nasal polyps:A Meta-analysis].

Objective:The relationship between viral infection and the occurrence of nasal polyps was explored to help us understand the etiology and pathogenesis of nasal polyps, and to provide scientific basis for the prevention and treatment of nasal polyps through a Meta-analysis. Method:By searching Pubmed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang Database, and VIP Database, time starts from database building until January 1, 2018, a comprehensive case-control study on the relationship between human papillomavirus, Epstein-Barr virus (EBV), respiratory virus infection and nasal polyps published at home and abroad has been conducted. At the same time, relevant literature references have been included and the full texts have been obtained. Stata 12.0 analysis software was used to perform statistical processing on each original data.Odds ratios (OR) and their 95% confidence interval (CI) were adopted to assess the strength of association. Result:21 articles with 24 studies were included on the relationship between HPV, EBV, respiratory viral infection and nasal polyps. The Meta-analysis results showed that the OR of HPV infection and nasal polyps was 6.74, 95%CI was 2.50－18.20, P<0.001, the OR of EBV and nasal polyps was 5.15, 95%CI was 1.66－16.02, P=0.005, the OR of respiratory viruses and nasal polyps was 1.68, 95%CI was 0.93－3.03, P=0.087.There was no significant publication bias in all of the comparisons. Conclusion:HPV and EBV infection were closely associated with the nasal polyps. Respiratory viral infection was not associated with the nasal polyps. Viral infection may be one of the etiologies of nasal polyps. It plays an important role in the pathogenesis of nasal polyps. The prevention and treatment of the virus infection should be targeted at early intervention.

Herpes viruses and human papilloma virus in nasal polyposis and controls / Herpesvírus e vírus do papiloma humano na polipose nasal e controles

ABSTRACT INTRODUCTION: Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. OBJECTIVE: To compare the prevalence of human herpes viruses (1-6) and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. METHODS: Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. RESULTS: Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4%) versus controls (4/38; 10.5%), but the difference did not reach significance (p = 0.06). Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29%) versus controls (10/38; 26.32%,p = 0.13). In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%), and another was cytomegalovirus-positive (1/91; 1.1%), versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and low-risk-human papilloma viruses (6, 11). CONCLUSION: Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis.

RESUMO INTRODUÇÃO: A rinossinusite crônica com pólipos é uma doença multifatorial de etiopatogênese ainda não definida. Existem dados contraditórios na literatura sobre a implicação potencial de elementos virais na etiologia de pólipos nasossinusais. OBJETIVO: Comparar a prevalência de herpes vírus humanos (1-6) e papiloma vírus humano em pacientes adultos com rinossinusite crônica com pólipos nasais (CRwNP) e controles saudáveis. MÉTODO: A presença de DNA viral foi avaliada por PCR em tempo real, em amostras de pólipos nasais de 91 pacientes com CRwNP e na mucosa das conchas nasais de 38 controles saudáveis. RESULTADOS: A positividade do EBV foi maior nos pólipos nasais (24/91; 26,4%) do que nos controles (4/38; 10,5%), mas a diferença não foi significante (p = 0,06). O HHV-6 apresentou positividade menor nos pólipos nasais (13/91; 14,29%) do que os controles (10/38; 26,32%), (p = 0,13). No grupo CRwNP, uma amostra foi positiva para o vírus herpes simples (HSV-1) (1/91; 1,1%), e uma para citomegalovírus (CMV) (1/91; 1,1%); e nenhuma amostra foi positiva no grupo controle. Não houve amostra positiva para HSV-2, VZV, HR-HPV (16,18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) e LR-HPV (6,11). CONCLUSÃO: Diferenças de positividade do EBV e HHV-6 entre pacientes com CRwNP e controles saudáveis não são estatisticamente significantes, enfraquecendo a probabilidade de sua implicação na patogênese da CRwNP.

Herpes viruses and human papilloma virus in nasal polyposis and controls.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. OBJECTIVE: To compare the prevalence of human herpes viruses (1-6) and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. METHODS: Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. RESULTS: Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4%) versus controls (4/38; 10.5%), but the difference did not reach significance (p=0.06). Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29%) versus controls (10/38; 26.32%, p=0.13). In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%), and another was cytomegalovirus-positive (1/91; 1.1%), versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and low-risk-human papilloma viruses (6, 11). CONCLUSION: Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis.

Evidence and role of autoantibodies in chronic rhinosinusitis with nasal polyps.

In this study, we review our current knowledge of the autoimmune etiopathogenesis of chronic rhinosinusitis with nasal polyps including bacterial infections, viral infections and immunomediated mechanisms and to discuss pathogenesis with relevance for pharmacotherapy. Relevant publications on the etiopathogenesis and treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) from 1977 to 2013 were analyzed. The characteristic signs and symptoms include appearance of relapsing nasal polyps, with typical symptoms such as nasal obstruction, nasal discharge and, usually, loss of the sense of smell. The etiology and pathogenesis remain unknown. Proposed theories of causation include bacterial or viral infections and immunomediated mechanisms. The autoimmune aetiology of unknown origin or failure to respond to classic pharmacological treatments with nasal and oral steroids is now suspected. At present, the nature of the antigen trigger, the exact role played by B/T cells and anti-dsDNA autoantibodies in the pathogenesis of nasal polyposis remains unclear. Corticosteroids and surgery are the first line of treatment in CRSwNP. In the case of corticosteroid treatment failure, other drugs can be used such as rituximab, belimumab or omalizumab which have demonstrated clinical efficacy in the treatment of nasal polyposis with comorbid asthma. Immunosuppressive drugs such as methotrexate, and cyclophosphamide have also been used with varying degrees of success.

Detection of herpesviruses 1-6 and community-acquired respiratory viruses in patients with chronic rhinosinusitis with nasal polyposis.

OBJECTIVE: To evaluate the prevalence of human herpesviruses (HHV) 1-6 and community-acquired respiratory viruses (CARVs) in specimens from patients with nasal polyposis undergoing functional endoscopic sinus surgery (FESS) and investigate the potential clinical role. METHODS: Viral occurrence was evaluated by molecular methods in polyp, turbinate mucosa, and pre- and postoperative scraping specimens from 35 consecutive patients at different time points in relation to FESS. RESULTS: Overall, 21 patients (60%) were positive to at least one virus in at least one specimen; in particular, 12.1% of all specimens for HHV-6 (3/35 polyps, 11/31 turbinates, 1 presurgical scraping) and 10.5% for Epstein-Barr virus (EBV) (8/35 polyps, 3/31 turbinates, 1/29 pre- and 1/29 postsurgical scraping), followed by CMV and HSV-1 (both 1.6%; 1/35 polyps, 1/29 postsurgical scraping and 2/35 polyps, respectively). EBV positivity tended to be higher in polyps, as well as HHV-6 in adjacent healthy turbinate mucosa, although no significant association was found. Only one preoperative cytological specimen was positive to parainfluenza virus-1. CONCLUSION: No association between the development of nasal polyps, herpesviruses and CARVs seems to exist. However, the higher EBV frequency in polyps could suggest a causative role or persistence in the inflammatory lymphoid tissue.

Prevalence of human papillomavirus, Epstein-Barr virus, p21, and p53 expression in sinonasal inverted papilloma, nasal polyp, and hypertrophied turbinate in Hong Kong patients.

BACKGROUND: The purpose of this study of human papillomavirus (HPV), Epstein-Barr virus (EBV), p21, and p53 in sinonasal inverted papilloma (IP) was to help elucidate its pathogenesis. METHODS: Seventy-three IPs, 48 nasal polyps, and 85 hypertrophied turbinates were subjected to HPV polymerase chain reaction (PCR) study. Seventy-three IPs, 30 nasal polyps, and 32 hypertrophied turbinates were subjected to EBV in situ hybridization (ISH), p21, and p53 immunohistochemical (IHC) studies. RESULTS: HPV was positive in 3 of 73 IPs (4.1%). All specimens were EBV negative. In all, 99% of IPs showed strong and diffuse p21 nuclear reactivity. Most nasal polyps and hypertrophied turbinates showed weak to moderate immunoreactivity of the basal and parabasal cells. Only focal p53 immunoreactivity of the basal and parabasal cells was found in 19% of IPs and 40% of nasal polyps. CONCLUSIONS: HPV prevalence of our IP is low. EBV is not present in IP. High p21 and low p53 expression in IP suggests a non-p53-dependent regulation pathway.

Levocetirizine inhibits rhinovirus-induced up-regulation of fibrogenic and angiogenic factors in nasal polyp fibroblasts.

BACKGROUND: Up-regulation of matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and transforming growth factor (TGF) beta, may contribute to the formation of nasal polyps (NPs). Rhinovirus (RV) infection enhances expression of MMP-2, MMP-9, and VEGF in NP fibroblasts and of TGF-beta in respiratory epithelial cells. We investigated the inhibitory effects of levocetirizine (LCT) on the RV-induced expression of (1) fibrogenic (MMPs and TGF-beta) and (2) angiogenic (VEGF and TGF-beta) factors in NP fibroblasts. METHODS: NP fibroblasts obtained from 11 male patients with chronic rhinosinusitis with NPs (CRSwNPs), were infected with RV serotype 16 (RV-16) for 4 hours. Cells were treated with 50 nM of LCT 24 hours before infection and for 48 hours thereafter. Expression of MMP-2, MMP-9, VEGF, and TGF-ß mRNA and protein were determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. RESULTS: LCT significantly inhibited RV-induced increases in MMP-2, MMP-9, VEGF, and TGF-beta mRNA, and protein expression, in NP fibroblasts (p < 0.05 for each comparison). CONCLUSION: LCT inhibits RV-induced up-regulation of fibrogenic and angiogenic factors in NP fibroblasts, suggesting that LCT may prevent NP formation in patients with CRSwNP caused by RV infection.

Human papillomavirus infection in nasal polyps in a Chinese population.

In order to determine the prevalence and genotype distribution of human papillomavirus (HPV) infection in patients with nasal polyps, a total of 204 patients with nasal polyps and 36 healthy controls were recruited for this study. Genomic DNA was extracted from paraffin-embedded tissue sections. HPV DNA genotyping was achieved by a flow-through hybridization and gene-chip method. HPV-positive infection was identified in 82 of 204 (40.2 %) patients, while HPV DNA was not found in healthy controls (P<0.05). Genotyping analysis showed that low-risk HPV genotype 11 was the most prevalent type of HPV in nasal polyps (45.28 %). Both single and multiple HPV genotype infections were found in these HPV-positive cases, although most (74.39 %) were infected with a single genotype. In addition, there was no correlation between HPV infection or HPV subtypes and the clinicopathological characteristics of patients, such as age, gender, number of surgery and disease course. The data from our study clearly demonstrated that HPV infection was associated with nasal polyps. Both high-risk HPV and low-risk HPV (LR-HPV) genotypes were identified in nasal polyp tissues, and LR-HPV-11 was the most prevalent type. Future research will explore the association of HPV infection with the development and progression of nasal polyps.

Is chronic rhinosinusitis caused by persistent respiratory virus infection?

BACKGROUND: Many chronic rhinosinusitis (CRS) patients recall an upper respiratory tract infection as the inciting event of their chronic illness. Viral infections have been shown to cause obstruction of the osteomeatal complex, which is likely to be a critical step in the development of CRS. There is clear overlap between the pathogenesis of CRS and asthma. Infections with respiratory viruses in childhood increase the risk of subsequently developing asthma. Viral infections in established asthmatics are associated with acute exacerbations. We sought to determine whether respiratory viruses could be detected within the sinonasal mucosa of CRS patients using polymerase chain reaction (PCR) techniques. METHODS: Sinus mucosa was sampled from 13 patients with CRS and 2 patients with normal sinuses. PCR was used to look for common respiratory viruses (parainfluenza 1, 2, and 3; respiratory syncytial virus [RSV]; human metapneumovirus [hMPV]; adenovirus [ADV]; rhinovirus; coronavirus; bocavirus [BoV]; cytomegalovirus [CMV]; and influenza A and B). RESULTS: No respiratory viruses were detected in any of the samples. CONCLUSION: Persistence of respiratory viruses within the sinonasal mucosa is unlikely to be a cause of ongoing inflammation in CRS. The possibility remains that a transient viral infection provides the initial inflammatory stimulus.

Enhanced susceptibility of nasal polyp tissues to avian and human influenza viruses.

BACKGROUND: Influenza viruses bind and infect respiratory epithelial cells through sialic acid on cell surface. Differential preference to sialic acid types contributes to host- and tissue-tropism of avian and seasonal influenza viruses. Although the highly pathogenic avian influenza virus H5N1 can infect and cause severe diseases in humans, it is not efficient in infecting human upper respiratory tract. This is because of the scarcity of its receptor, α2,3-linked sialic acid, in human upper airway. Expression of sialic acid can be influenced by various factors including inflammatory process. Allergic rhinitis and nasal polyp are common inflammatory conditions of nasal mucosa and may affect expression of the sialic acid and susceptibility to influenza infection. METHODOLOGY/PRINCIPAL FINDING: To test this hypothesis, we detected α2,3- and α2,6-linked sialic acid in human nasal polyp and normal nasal mucosal tissues by lectin staining and infected explants of those tissues with avian influenza viruses H5N1 and seasonal influenza viruses. We show here that mucosal surface of nasal polyp expressed higher level of α2,3- and α2,6-linked sialic acid than normal nasal mucosa. Accordingly, both H5N1 avian influenza viruses and seasonal influenza viruses replicated more efficiently in nasal polyp tissues explants. CONCLUSIONS/SIGNIFICANCE: Our data suggest a role of nasal inflammatory conditions in susceptibility to influenza infection, especially by avian influenza viruses, which is generally inefficient in infecting human upper airway. The increased receptor expression may contribute to increased susceptibility in some individuals. This may contribute to the gradual adaptation of the virus to human population.

[The role of infection in the development of polypous rhinosinusitis in patients with bronchial asthma].

At present, many authors accept the many-factor theory of development of polypous rhinosinusitis associated with bronchial asthma according to which this condition should be regarded as an inflammatory syndrome in subjects predisposed to a specific tissue reaction. Inflammation induced by an infection is accompanied by the release of protease-inhibiting enzymes that turn inflammation into a chronic process thereby contributing to tissue disintegration, remodeling of mucous membranes, and development of polyps.

Rhinovirus-infected nasal polyp epithelial cells: effect on the activation and migration of eosinophils by airborne fungi.

BACKGROUND: Rhinovirus and fungi are common environmental factors able to induce airway inflammation. They are associated with the production of chemical mediators by direct activation of epithelial cells. OBJECTIVE: To evaluate the effect of fungal stimulation of rhinovirus-infected nasal polyp epithelial cells (NPECs) on the activation and migration of eosinophils. METHODS: Rhinovirus-infected NPECs were stimulated with Alternaria and Aspergillus for 48 hours. Then, epithelial cells were co-cultured with freshly isolated eosinophils. An eosinophil migration study was performed with epithelial cell-conditioned media. Interleukin 6, interleukin 8, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor levels were measured to determine the activation of cells. RESULTS: Airborne fungi enhanced the production of cytokines from rhinovirus 16-infected NPECs compared with fungi stimulation or rhinovirus 16 infection alone. Rhinovirus 16-infected NPECs were co-cultured with eosinophils, and cytokine production was not significantly increased except tumor necrosis factor-alpha production by Aspergillus. Epithelial cell-conditioned media, which were stimulated with fungi, enhanced the migration of eosinophils. CONCLUSIONS: There was some synergism between rhinovirus 16 infection and airborne fungal exposure, enhancing the inflammatory response of airway epithelial cells.

Prevalence of human papilloma virus and human herpes virus types 1-7 in human nasal polyposis.

This study aimed to investigate the prevalence of human papilloma virus (HPV), herpes simplex virus-1/-2 (HSV-1/-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6/-7 (HHV-6/-7) in 23 human nasal polyps by applying PCR. Two types of control tissues were used: adjacent inferior/middle turbinates from the patients and inferior/middle turbinates from 13 patients undergoing nasal corrective surgery. EBV was the virus most frequently detected (35%), followed by HPV (13%), HSV-1 (9%), and CMV (4%). The CMV-positive polyp was simultaneously positive for HSV-1. HPV was also detected in the adjacent turbinates (4%) and the adjacent middle turbinate (4%) of one of the HPV-positive patients. EBV, HSV, and CMV were not detected in the adjacent turbinates of the EBV-, HSV- or CMV-positive patients. All mucosae were negative for the VZV, HHV-6, and HHV-7. This is the first study to deal with the involvement of a comparable group of viruses in human nasal polyposis. The findings support the theory that the presence of viral EBV markedly influences the pathogenesis of these benign nasal tumors. The low incidence of HPV detected confirms the hypothesis that HPV is correlated with infectious mucosal lesions to a lesser extent than it is with proliferative lesions, such as inverted papilloma. The low incidence of HSV-1 and CMV confirms that these two herpes viruses may play a minor role in the development of nasal polyposis. Double infection with HSV-1 and CMV may also play a minor, though causative, role in nasal polyp development. VZV and HHV-6/-7 do not appear to be involved in the pathogenesis of these mucosal lesions.

Infection rate and virus-induced cytokine secretion in experimental rhinovirus infection in mucosal organ culture: comparison between specimens from patients with chronic rhinosinusitis with nasal polyps and those from normal subjects.

OBJECTIVE: To investigate the difference in susceptibility to rhinovirus (RV) infection and RV-induced inflammatory response between the nasal mucosae from patients with chronic rhinosinusitis with nasal polyps (CRS/NP) and subjects without CRS/NP (hereinafter, normal subjects). DESIGN: In vitro study. SETTING: Tertiary care rhinology clinic. PATIENTS: We conducted RV infection experiments on the organ cultures of NPs and inferior turbinate mucosae from 16 patients with CRS/NP and sphenoid sinus and inferior turbinate mucosae from 19 patients who underwent transsphenoidal pituitary surgery. MAIN OUTCOME MEASURES: Successful RV-16 infection was determined by positive identification of RV on the surface fluid of organ culture using seminested reverse transcriptase-polymerase chain reaction. Effects of RV on interleukin 6 (IL-6) and IL-8 secretion were measured by enzyme-linked immunosorbent assay. RESULTS: The successful RV infection was achievable in 9 of 16 NP samples (56.3%) and 9 of 16 turbinate samples (56.3%) from patients with CRS/NP compared with 11 of 19 sphenoid sinus samples (57.9%) and 15 of 19 turbinate samples (78.9%) from normal subjects. The RV infection increased IL-6 and IL-8 secretion 236% and 173%, respectively, in NP samples, and 218% and 178%, respectively, in turbinate samples from patients with CRS/NP; compared with 231% and 145%, respectively, in sphenoid mucosa samples, and 181% and 148%, respectively, in turbinate samples from normal subjects. However, there were no statistical differences among the 4 groups. CONCLUSION: These in vitro findings suggest that subjects with CRS/NP mucosa might not be more susceptible to RV infection, and did not secrete more cytokines in response to rhinovirus infection, than those with normal mucosa.

Detection of human papillomavirus DNA in benign and malignant sinonasal neoplasms.

Infections with human papillomaviruses are divided basically into three different infection types: those producing specific clinically visible lesions, those remaining subclinical, and those being latent. The assumed infection type thought to be present in tissue specimens has influence on the conclusions that can be made from an analysis, i.e. whether or not the HPV infection has a causal relationship with other epidemiological or molecular investigation observations. To determine whether HPV DNA detection in different entities of the upper aerodigestive tract represents a coincidental, persistent/latent or specific infection, 20 clinically intact mucosa specimens of the upper aerodigestive tract, 20 sinonasal polyps, 26 inverted papillomas, and 20 squamous cell carcinomas of the paranasal sinuses were investigated. HPV DNA was not detectable in specimens derived from clinically intact mucosa or in nasal polyps. Yet, three out of 26 inverted papillomas were HPV-positive, each showing double infection with HPV6 and 11. Four out of 20 squamous cell carcinomas were HPV16 positive. To our knowledge, we are presenting the first study contemporaneously analyzing benign as well as malignant non-proliferative and proliferative mucosal entities whilst applying identical methodical standards. The data corroborate the hypothesis that HPV DNA demonstration in tissue specimens represents a specific infection of the mucosa of the upper aerodigestive tract. It can thus be assumed that there is a causative involvement of HPV infections in the alteration of cell proliferation and in the case of infection with high risk HPV types even on progression to malignant transformation.