Aspects of Langerhans cells and TNF-α in the cutaneous immunity of anogenital warts

Abstract Background: Anogenital warts are the leading sexually transmitted infection in patients seeking care at specialized clinics. They may display a vast array of forms, according to the interaction of the virus with the host's immunity. Cellular immunity is the epithelium's main form of defense against the virus, involving an active participation of the Langerhans cells and pro-inflammatory cytokines such as TNF-α. Objective: To assess the epithelial immune response of anogenital warts in males, according to the number of lesions presented. Methods: This is a prospective, cross-sectional study carried out at the dermatology outpatient clinic in a tertiary hospital. We included male patients over 18 years of age without comorbidities who had anogenital condylomata and no previous treatments.In order to evaluate the local epithelial immunity, the lesions were quantified, then removed and employed in CD1a immunohistochemistry assays for assessing the morphometry and morphology of Langerhans cells; TNF-α; reaction was used for determining cytokine positivity in the epithelium. Results: 48 patients were included in the study. There was no statistically significant difference as to the number of Langerhans cells, in their morphology, or the presence of TNF-α. However, patients presenting with more Langerhans cells in the lesions had cells with a star-like and dendritic morphology, whereas in those with a lower cell count had cells with a rounded morphology and no dendrites (p < 0.001). Study limitations: Small number of patients analyzed. Conclusion: There was no difference in epithelial immunity between patients having few or many anogenital condyloma lesions as measured by the morphology and morphometry of Langerhans cells and TNF-α; positivity. Such an assessment employing immunity markers differing from the usual ones is expected to yield useful results.

Can quadrivalent human papillomavirus prophylactic vaccine be an effective alternative for the therapeutic management of genital warts? an exploratory study

ABSTRACT Objective: To evaluate the treatment effect of genital warts, we investigated the quadrivalent HPV vaccine injection compared with surgical excision. Materials and Methods: This prospective study included 26 patients (M:F = 24:2) who received HPV vaccine or surgical excision. After explanation of surgical excision or HPV vaccine, 16 patients underwent surgical excision and the others received HPV vaccine injections. Based on gross findings of genital warts, treatment outcomes were classified as complete response (no wart), partial response, and failed treatment. Results: Among enrolled patients, 42% (11 / 26) patients had recurrent genital warts. In vaccination group, complete response rates of genital wart were 60% following 3 times HPV vaccine. Partial response patients wanted to excise the genital lesions before the 3 times injection, because they worried about sexual transmission of disease to their sexual partners. One patient underwent surgical excision after 3 times injection. Excision sites included suprapubic lesions, but other sites including mid-urethra and glans showed complete response after injection. At a mean follow-up period of 8.42 ± 3.27 months, 10 patients (100%) who received HPV vaccine did not show recurrence. Conclusion: The response rates after HPV vaccine injection were 90% (complete and partial). Our results suggested that HPV vaccines could be effective in management of genital warts.

Morphometric analysis of dendritic cells from anal mucosa of HIV-positive patients and the relation to intraepithelial lesions and cancer seen at a tertiary health institution in Brazil / Análise morfométrica das células dendríticas da mucosa anal de pacientes HIV-positivos e relação com as lesões intraepiteliais e o câncer numa instituição de saúde terciária no Brasil

PURPOSE: To morphometrically quantify CD1a+ dentritic cells and DC-SIGN+ dendritic cells in HIV-positive patients with anal squamous intraepithelial neoplasia and to evaluate the effects of HIV infection, antiretroviral therapy and HPV infection on epithelial and subepithelial dendritic cells. METHODS: A prospective study was performed to morphometrically analyze the relative volume of the dendritic cells and the relationship between anal intraepithelial neoplasia and cancer in HIV-positive patients from the Tropical Medicine Foundation of Amazonas, Brazil. All patients were submitted to biopsies of anorectal mucosa to perform a classic histopathological and immunohistochemical analysis, employing antibodies against CD1a and DC-SIGN for the morphometric quantification of dendritic cells. RESULTS: HIV-negative patients displayed a CD1a DC density significantly higher than that of HIV-positives patients (3.75 versus 2.54) (p=0.018), and in patients with severe anal intraepithelial neoplasia had correlated between DC CD1a density with levels of CD4 + cells (p: 0.04) as well as the viral load of HIV-1 (p: 0.035). A not significant rise in the median density of CD1a+ DC was observed in the HIV positive/ HAART positive subgroup compared to the HIV positive/ HAART negative subgroup. The CD1a+ DC were also significantly increased in HIV-negative patients with anorectal condyloma (2.33 to 3.53; p=0.05), with an opposite effect in HIV-positive patients. CONCLUSIONS: Our data support an enhancement of the synergistic action caused by HIV-HPV co-infection on the anal epithelium, weakening the DC for its major role in immune surveillance. Notoriously in patients with severe anal intraepithelial neoplasia, the density of CD1a+ epithelial dendritic cells was influenced by the viral load of HIV-1. Our study describes for the first time the density of subepithelial DC-SIGN+ dendritic cells in patients with anal severe anal intraepithelial neoplasia and points to the possibility that a specific therapy for HIV induces the recovery of the density of epithelial DC.

OBJETIVO: Quantificar morfometricamente as células dendríticas DC CD1a+ e DC DC-SIGN+ em pacientes HIV positivos portadores de neoplasia escamosa intraepitelial anal e avaliar os efeitos da infecção pelo HIV, da terapia antirretroviral e da infecção pelo HPV sobre as células dendríticas epiteliais e subepiteliais. MÉTODOS: Um estudo prospectivo foi realizado para analisar morfometricamente o volume relativo das células dendríticas e as relações entre neoplasia intraepitelial anal e o câncer em pacientes HIV positivos da Fundação de Medicina Tropical do Amazonas, Brasil.Todos os pacientes foram submetidos a biópsia da mucosa retal para realizar uma análise clássica histopatológica e imunohistoquímica utilizando anticorpos contra anti-CD1a e anti-DC-SIGN, para a quantificação morfométrica das células dendríticas. RESULTADOS: Os pacientes HIV negativos apresentaram densidade das DC CD1a+ significativamente maior do que a dos pacientes HIV positivos (3,75 versus 2,54) (p:0,018), e os pacientes com severa apresentaram correlação das DC CD1a com os níveis de células TCD4(p:0,04) assim como a carga viral do HIV-1 (p:0,035). Observamos no subgrupo HIV-positivo/HAART positivo elevação não significativa na mediana da densidade das DC CD1a+ em relação ao grupo HIV-positivo/HAART negativo. As DC CD1a+ também se elevaram nos pacientes HIV negativo portadores de condiloma anorretal(2,33 para 3,53; p:0,05), com efeito inverso nos pacientes HIV positivos. CONCLUSÕES: Nossos dados confirmam a potencialização da ação sinérgica representada pela coinfecção HIV-HPV sobre o epitélio anal, fragilizando as DC em sua função primordial de vigilância imune. Notoriamente nos pacientes com neoplasia intraepithelial anal grave, a densidade das DC CD1a+ epiteliais sofreu influência da carga viral do HIV-1. Nosso estudo descreveu pela primeira vez a densidade das DC subepiteliais DC-SIGN+ em pacientes com neoplasia intraepithelial anal severa e apontamos para a possibilidade de que a terapia específica para o HIV induza a recuperação da densidade das DC epiteliais.

Estudio inmunohistoquímico de antígenos del condiloma y carcino embrionario en el cérvix uterino con infección por virus del papiloma humano y con neoplasia / Immunohistochemical study of condyloma and carcino embryonic antigens in uterine cervix infected with human papilloma virus and with neoplasim

Con la técnica de inmunoperoxidasa PAP se intentó demostrar antígeno carcinoembrionario (ACE) en 37 biopsias de cérvix divididas en 4 grupos: 1) condiloma solo, 2) condiloma con neoplasia intraepitelial cervical (NIC), 3) carcinoma epidermoide invasor solo y 4) cérvix normal y con inflamación crónica. De las 37 biopsias 22 correspondieron a condiloma solo y condiloma asociado a NIC de diversos grados, y en 20 de ellas o sea 90,9% se obtuvieron resultados positivos. En los 7 caos de carcinoma epidermoide in situ e infiltrante la reacción también resultó positiva para ACE. Con la misma técnica se estudiaron 20 biopsias de cérvix de los 4 grupos, para tratar de demostrar antígenos de condiloma: únicamente en las 5 muestras de condiloma solo y en 3 de 4 condiloma, con NIC las reacciones fueron positivas. En cambio, en el carcinoma invasor y en el cérvix y con inflamación crónica, la reacción resultó negativa. Se concluyó que los signos histomorfológicos de infección cervical por virus del papiloma tiene un alto grado de certeza, que aparentemente la infección por virus del papiloma provoca una alteración en la diferenciación celular que se manifiesta por reaparición de ACE, y que el virus del papiloma probablemente juega un papel muy importante en la oncogénesis del carcinoma cervicouterino