Effectiveness of the AS04-adjuvanted HPV-16/18 vaccine in reducing oropharyngeal HPV infections in young females-Results from a community-randomized trial.

We studied effectiveness of the AS04-adjuvanted HPV-16/18 (AS04-HPV-16/18) vaccine against human papillomavirus (HPV) oropharyngeal infections associated with the increase of head/neck cancers in western countries. All 38,631 resident adolescents from 1994 to 1995 birth cohorts of 33 Finnish communities were invited in this community-randomized trial (NCT00534638). During 2008-2009, 11,275 girls and 6,129 boys were enrolled in three arms of 11 communities each. In Arm A, 90% of vaccinated girls/boys, and in Arm B, 90% of vaccinated girls received AS04-HPV-16/18 vaccine. Other Arm A/B and all Arm C vaccinated participants received control vaccine. All Arm A participants and Arm B female participants were blinded to vaccine allocation. Oropharyngeal samples were analyzed from 4,871 18.5-year-old females who attended follow-up visit 3-6 years postvaccination. HPV DNA prevalence was determined by SPF-10 LiPA and Multiplex type-specific PCR. Total vaccine effectiveness (VE) was defined as relative reduction of oropharyngeal HPV prevalence in pooled Arms A/B HPV-vaccinated females vs. all Arm C females. VE against oropharyngeal HPV-16/18, HPV-31/45 and HPV-31/33/45 infections were 82.4% (95% confidence intervals [CI]: 47.3-94.1), 75.3% (95%CI: 12.7-93.0) and 69.9% (95% CI: 29.6-87.1), respectively. In conclusion, the AS04-HPV-16/18 vaccine showed effectiveness against vaccine and nonvaccine HPV-types oropharyngeal infections in adolescent females up to 6 years postvaccination.

Oropharyngeal histoplasmosis: a report of 10 cases.

A wide differential diagnosis must be entertained in patients with unusual oral and pharyngeal ulcerations. A mucosal biopsy is essential. We retrospectively reviewed 10 cases from the Infectious Diseases Division at Mayo Clinic Rochester (MN, USA), in which the diagnosis proved to be Histoplasma capsulatum infection. Between 1995 and 2016, 10 patients were diagnosed with oropharyngeal histoplasmosis. Common presenting symptoms included weight loss, weakness and oropharyngeal pain with ulcerations. Despite specialty evaluation at other facilities, diagnostic delay occurred in six patients due to lack of biopsy or fungal staining. Yeast forms consistent with H. capsulatum were identified in the biopsy specimens of all our patients. Treatment included intravenous amphotericin B and prolonged courses of azoles. Oral histoplasmosis occurred in both immunocompetent and immunosuppressed patients, and was a manifestation of disseminated infection. Severe pain involving all areas of the mouth was typical. Diagnostic delay may be avoided by early biopsy using fungal stains.

Clinical Manifestations of IgG4-Related Disease in the Pharynx: Case Series and Review of the Literature.

OBJECTIVE: The objective of this report is to characterize IgG4-related disease (IgG4-RD) as it is manifested in the head and neck and describe a series of patients with a rarely described presentation in laryngopharyngeal subsites. METHODS: Here, we illustrate the presentation and clinical course of 3 patients with laryngopharyngeal manifestations of IgG4-RD, including the manner of diagnosis and effective treatment. RESULTS: Three patients with laryngopharyngeal lesions were ultimately diagnosed with IgG4-RD after lengthy work-up. The diagnostic criteria and treatment protocols are explained. CONCLUSION: IgG4-related disease is a fibroinflammatory disorder now described in almost every organ system. The head and neck regions are among the most common areas of involvement, however, reports of laryngopharyngeal involvement are rare. We also summarize current knowledge of this entity and discuss established diagnostic criteria and clinical findings.

Autoimmune disease as a risk factor for globus pharyngeus: a cross-sectional epidemiological study.

OBJECTIVE: To assess the prevalence and severity of globus-type symptoms in individuals who have a prior diagnosis of autoimmune disease. DESIGN: Cross-sectional questionnaire. PARTICIPANTS AND SETTING: One hundred and nine patients with autoimmune disease (rheumatoid arthritis, seronegative spondarthritis, connective tissue disease, systemic vasculitis) and 41 patients with non-autoimmune disease (osteoarthritis/osteoporosis) attending a rheumatology tertiary referral clinic at Norfolk & Norwich University Hospitals NHS Foundation Trust. The results from this study were compared to previous published figures in patients with globus pharyngeus (n = 105) and normal population (n = 174). MAIN OUTCOME MEASURES: Glasgow Edinburgh Throat Scale questionnaire; Reflux Symptom Index; Anxiety/Depression Scale. RESULTS: Patients with autoimmune disease demonstrate a significantly higher prevalence for 5/10 symptoms on the Glasgow Edinburgh Throat scale score when compared to the non-autoimmune control group (P ≤ 0.01). This significant difference increases to 9/10 symptoms when compared to published results for the normal population (P = 0.01). No significant difference was found when comparing the autoimmune and non-autoimmune control group reflux symptom index (P = 0.64) or anxiety depression scale (P = 0.71). CONCLUSION: Patients with autoimmune disease have a significantly increased prevalence of globus symptoms when compared to the healthy population. A further prospective study is required to decipher the effect of pharmacotherapy as a possible causative factor.

[Morphological and immunohistochemical studies of palatine tonsillar hypertrophy in children].

The paper presents the results of immunohistochemical and morphometric studies conducted to examine an association of the site, the expression of virus antigens, and the nature of morphological changes in the hypertrophic palatine tonsils in children. The distribution of CD3+ and CD20+ cells was explored in tonsillar tissue. The greatest changes were shown in the epithelium, the antigens of herpex simplex virus being more frequently detected than those of human papillomavirus. The presented data may be suggestive of the important role of viruses in the development of palatine tonsillar pathology, different protective reactions of various palatine tonsillar structures, which should be borne in mind during etiopathogenetic therapy.

Laryngopharyngeal reflux: diagnosis and treatment of a controversial disease.

PURPOSE OF REVIEW: Laryngopharyngeal reflux is a well-recognized and widely used term in ear, nose and throat practice. However, the symptoms and signs attributed to laryngopharyngeal reflux are non-specific and treatment is usually empirical. This review discusses current knowledge on diagnosis and treatment of laryngopharyngeal reflux. RECENT FINDINGS: Information is evolving regarding the implications of laryngopharyngeal reflux in the development of pathological conditions affecting the upper aerodigestive tract epithelium such as chronic laryngitis, otitis media with effusion and chronic sinusitis. However, there is still much to learn about the pathophysiologic mechanisms of laryngopharyngeal reflux and their role in its related disease conditions and there is still considerable controversy on diagnostic as well as therapeutic parameters for this condition. There is no consensus on the diagnosis and treatment of laryngopharyngeal reflux and the majority of clinicians depend mainly on clinical findings and empirical therapeutic tests rather than more specific investigations. SUMMARY: The concept of laryngopharyngeal reflux is still controversial. The current practice of empirical treatment with proton-pump inhibitors is based on weak evidence. However, this practice seems to be widely accepted and will not change until further clinical and laboratory studies improve our understanding of this common and well-recognized condition.

A prospective study of upper aerodigestive tract manifestations of mucous membrane pemphigoid.

We conducted a prospective study between 1995 and 2002 to investigate nose and throat (NT) manifestations of mucous membrane pemphigoid (MMP). One hundred ten consecutive patients with clinical, histologic, and immunologic criteria of MMP were seen in 2 referral centers for bullous diseases. They were systematically asked about the existence of persistent NT symptoms. Patients who had any were examined with a flexible nasopharyngolaryngoscope by the same otorhinolaryngologist. When possible, NT mucous membrane (MM) biopsies were taken for direct immunofluorescence (IF) assays to determine lesion specificity. Thirty-eight (35%) patients (23 F/15 M; mean age, 58.5 yr) had the following NT symptoms: 35 (92%) nasal, 19 (50%) pharyngeal, and 10 (26%) laryngeal. Five (13%) had acute dyspnea. Thirty-three (87%) of the 38 symptomatic patients had lesions at physical examination: 30 (79%) nasal, 6 (16%) pharyngeal, and 19 (50%) laryngeal. Laryngeal involvement was asymptomatic in 11 patients. Lesions were mainly atrophic rhinitis and oropharyngeal and epiglottal erosions. Nasal valves, choanae, pharynx, and/or larynx were severely scarred in 7 (18%) patients, causing the death of 3. Direct IF showed malpighian epithelium associated with linear immune deposits (IgG, IgA, or C3) along the chorioepithelial junction in all 18 biopsies performed, including those of 4 symptomatic patients without lesions at physical examination. The presence of severe ophthalmologic lesions (p = 0.02) and > or =3 sites involved other than NT (p = 0.02) were predictive of laryngeal involvement. In contrast, laryngeal symptoms, disease duration, HLA DQB1*0301, and smoking were not significantly associated with laryngeal lesions. In conclusion, at least 35% of MMP patients had NT involvement. Atrophic rhinitis was the most frequent lesion. The most severe were the laryngeal lesions that were significantly associated with severe ocular involvement and disseminated disease, and could be fatal. Our results highlight the necessity of a multidisciplinary approach to MMP management to assure early diagnosis of NT involvement, to guide therapeutic choices, and to improve patient survival and functional outcomes.

The host cytokine responses and protective immunity in oropharyngeal candidiasis.

Over the last three decades, the prevalence of oropharyngeal fungal infections has increased enormously, mainly due to an increasing population of immunocompromised patients, including individuals with HIV infection, transplant recipients, and patients receiving cancer therapy. The vast majority of these infections are caused by Candida species. The presence of cytokines in infected tissues ultimately dictates the host defense processes that are specific to each pathogenic organism. During oral infection with Candida, a large number of pro-inflammatory and immunoregulatory cytokines are generated in the oral mucosa. The main sources of these cytokines are oral epithelial cells, which maintain a central role in the protection against fungal organisms. These cytokines may drive the chemotaxis and effector functions of innate and/or adaptive effector cells, such as infiltrating neutrophils and T-cells in immunocompetent hosts, and CD8(+) T-cells in HIV(+) hosts. Epithelial cells also have direct anti-Candida activity. Several studies have provided a potential link between lower levels of certain pro-inflammatory cytokines and susceptibility to oral C. albicans infection, suggesting that such cytokines may be involved in immune protection. The exact role of these cytokines in immune protection against oropharyngeal candidiasis is still incompletely understood and requires further investigation. Identification of such cytokines with the ability to enhance anti-fungal activities of immune effector cells may have therapeutic implications in the treatment of this oral infection in the severely immunocompromised host.

Host pathogen interaction and the development of oral lesions.

The aetiologies of oral ulceration, disseminated interstitial lymphocytosis syndrome and oral lymphomas have been reviewed, with emphasis on the role of HIV infection in the primary causation or modification of the presentation of these entities. There is a paucity of evidence to explain why oral ulceration is so severe in HIV infection, and why major ulceration affects the oropharynx. A number of mechanisms have been proposed to account for the development of lymphomas in patients with HIV infection, including a genetic predisposition, decreased immunosurveillance due to HIV infection, alteration of endothelial cell function and dysregulation of cytokine networks. From this review, it was concluded that there is a need for a prospective multicentre study, to elucidate the aetiological mechanisms involved in lymphomas of the oral regions in this patient group. It was concluded that, although there is anecdotal evidence implicating tobacco use in the aetiology of the lesions reviewed, this is insufficient to allow definitive statements to be made and further systematic evaluation is indicated.

T cells augment monocyte and neutrophil function in host resistance against oropharyngeal candidiasis.

The purpose of this study was to identify the cell populations involved in recovery from oral infections with Candida albicans. Monoclonal antibodies specific for CD4+ cells, CD8+ cells, and polymorphonuclear leukocytes were used to deplete BALB/c and CBA/CaH mice of the relevant cell populations in systemic circulation. Monocytes were inactivated with the cytotoxic chemical carrageenan. Mice were infected with 10(8) C. albicans yeast cells and monitored for 21 days. Systemic depletion of CD4+ and CD8+ T lymphocytes alone did not increase the severity of oral infection compared to that of controls. Oral colonization persisted in animals treated with head and neck irradiation and depleted of CD4+ T cells, whereas infections in animals that received head and neck irradiation alone or irradiation and anti-CD8 antibody cleared the infection in a comparable fashion. The depletion of polymorphonuclear cells and the cytotoxic inactivation of mononuclear phagocytes significantly increased the severity of oral infection in both BALB/c and CBA/CaH mice. High levels of interleukin 12 (IL-12) and gamma interferon (IFN-gamma) were produced by lymphocytes from the draining lymph nodes of recovering animals, whereas IL-6, tumor necrosis factor alpha, and IFN-gamma were detected in the oral mucosae of both naïve and infected mice. The results indicate that recovery from oropharyngeal candidiasis in this model is dependent on CD4+-T-cell augmentation of monocyte and neutrophil functions exerted by Th1-type cytokines such as IL-12 and IFN-gamma.

Low levels of antigenic variability in fluconazole-susceptible and -resistant Candida albicans isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis.

Three serial isolates of Candida albicans were obtained by direct swab or by oral saline rinses from each of five human immunodeficiency virus-infected patients with recurrent oropharyngeal candidiasis. Genotyping techniques confirmed the presence of a persistent strain in multiple episodes from the same patient, which was different from the strains isolated from other patients. Fluconazole susceptibility was determined by both an agar dilution method and the National Committee for Clinical Laboratory Standards macrobroth procedure. In four of these patients the strains developed fluconazole resistance, and in one patient the strain remained susceptible. The different isolates were propagated as yeast cells on a synthetic medium, and their cell wall proteinaceous components were extracted by treatment with beta-mercaptoethanol. Protein and mannoprotein components present in the extracts were analyzed by electrophoresis, immunoblotting, and lectin-blotting techniques. The analysis showed a similar composition, with only minor qualitative and quantitative differences in the polypeptidic and antigenic patterns associated with the cell wall extracts from serial isolates from the same patient, as well as those from different strains isolated from different patients. Use of monospecific antibodies generated against two immunodominant antigens during candidiasis (enolase and the 58-kDa fibrinogen-binding mannoprotein) demonstrated their expression in all isolates tested. Overall, the antigenic makeup of C. albicans strains remained constant during the course of infection and was not affected by development of fluconazole resistance. In contrast to previous reports, the low degree of antigenic variability observed in this study may be due to the fact that the isolates were obtained from a highly homogeneous population of patients and to the uniformity in techniques used for the isolation, storage, and culture of the different strains, as well as extraction methodologies.

Pharyngeal edema caused by occupational exposure to cellulase enzyme.

Enzymes can cause allergic asthma and rhinitis. Although patients sometimes complain of symptoms in their throat, we have not been able to find any published report of pharyngeal edema caused by exposure to enzymes. We present the case of a maintenance foreman who worked in a factory producing enzymes, and who had pharyngeal edema, asthma, and rhinitis at work. Prick tests for cellulase enzyme and cellulase RAST were positive. The causal association between his pharyngeal symptoms and cellulase was demonstrated with inhalation provocation tests in an exposure chamber.

[Treatment of oropharyngeal and esophageal mycoses in immunodeficient patients with fluconazole (Diflucan, Pfizer)]. / Lécba orofaryngeální a jícnové mykózy u imunodeficitních nemocných Fluconazolem (Diflucan, Pfizer).

Thirteen patients with oropharyngeal and oesophageal mycosis were treated with a new triazole antimycotic, fluconazole. In the whole group in addition to the basic neoplastic disease as multifactorial predisposition to mycotic infection was revealed. After treatment a 100% clinical as well a laboratory effect was achieved. However, within one month a relapse developed in three of eight patients and reinfection in four of eight (renewal of laboratory evidence). The preparation was well tolerated by the patients, no laboratory signs of organ toxicity were revealed. In patients with cumulation of predisposing factors for mycotic infection the authors recommend long-term prophylactic protection with a small dose of fluconazole.

Rotavirus infection of the oropharynx and respiratory tract in young children.

Oropharyngeal aspirates were obtained from 89 infants hospitalized with respiratory illnesses accompanied or not by diarrhea and 33 control patients without the diseases. Rotavirus was detected from 25 of these patients by immunocytology, isolation of the virus in cultures of MA104 cells, or both. None of the control patients gave a positive result. The infection involves squamous cells and globlet cells probably originating from the oropharynx, and ciliated columnar epithelial cells from the respiratory tract. The virus from 2 specimens was propagated by repeatedly passaging in the cultures and found to have characteristic morphology of rotavirus. The electrophoretic patterns of the viral RNA extracted from them are closely similar to those obtained with the rotavirus genome extracted from the stool of the same patients. Repeated stool specimens were also obtained, and sera were paired from some of these subjects. All but one of the patients who gave a positive virology for their aspirates also showed a significant rise in the titres of common group A rotavirus antibody, neutralizing antibody against one or more of serotypes of rotavirus, or both. Patients who excreted rotavirus in their stools were younger and had significantly lower titres of rotavirus antibodies in their acute sera, than those who shedded the virus in the oropharynx but did not excrete the virus in repeated stool specimens. The prevalence of rotavirus in the oropharyngeal aspirates from these patients surpassed that of adenovirus, respiratory syncytial virus, influenza virus, and herpes simplex virus combined.

Immunity to mycoplasmal infection of the genital tract: a mouse model.

Thirty-three TO mice, 24 of which had received progesterone, were infected originally by Mycoplasma pulmonis given vaginally. Thirty-one of the mice were free of the organisms in the genital tract 236 days later at which time all of them were treated again with progesterone and rechallenged with M. pulmonis vaginally. All 31 mice were resistant. In contrast, of 21 TO mice of the same age that were not infected originally 15 (71%) became infected persistently after vaginal rechallenge. In similar experiments, 12 CBA mice, nine of which had received progesterone, were infected originally. Ten of these mice were free of the organisms genitally 2 years later, at which time all of them were rechallenged vaginally. Only two mice (20%) were reinfected, whereas six (86%) out of seven mice, not infected originally, were reinfected. Autopsy examination revealed that neither infection nor immunity was confined to the lower genital tract. Thus, M. pulmonis organisms were not detected in the upper tract of five TO mice that remained mycoplasma-free vaginally after rechallenge. The contribution of oropharyngeal M. pulmonis infection, which occurred in most of the mice, to the solid, long-lasting genital-tract resistance was difficult to assess, but in two mice, at least, immunity was not afforded by such infection.

Proliferation of T gamma cells with killer-cell activity in two patients with neutropenia and recurrent infections.

Two patients with severe granulocytopenia and recurrent infections of the skin and oropharynx had excess T lymphocytes with receptors for the Fc portion of IgG (T gamma cells) in blood and bone marrow. The abnormal T gamma cells killed antibody-sensitized target cells in vitro (killer-cell activity) but did not suppress immunoglobulin production by B lymphocytes (suppressor-cell activity). T gamma lymphocytes from normal persons showed both killer-cell activity and suppressor-cell activity. In the serum of one patient, granulocyte antibodies, possibly of an autoimmune nature, were detected. The clinical picture in conjunction with the hematologic and immunologic findings characterized the disease of both patients as a distinct entity among the chronic lymphoproliferative diseases of T-cell origin.

Otolaryngeal allergy in Wellington. 1971-1975.

Two thousand and twenty-nine patients received allergic therapy 1971-1975. Nine hundred and eighty-nine were followed up six to 24 months later. All received Rinkel's inhalant skin titration method. The first group 1971-1972 of 309 patients were investigated with Lee's food provocation method and useful relief of symptoms occurred in 27.6 per cent of patients. The second group 1973-1975 of 680 patients were investigated with Bryan's cytotoxic food test, 60 percent reported very good relief and 26 percent useful relief of symptoms. Successfully treated patients were able to curtail or abandon drug therapy and the frequency of surgery was decreased. The authors believe allergic symptoms are of common occurrence in patients frequently seeking medical attention.