Avaliação da resposta clínica e imunológica local de pacientes com neoplasia intra-epitelial cervical graus II e III tratadas com interferon alfa-2b intralesional.

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

Introduction: HPV is a DNA virus of tape double which can infect the lower genital tract. Its persistence, especially with oncogenic types is highly associated with the development of the high-grade squamous intraepithelial lesions. Treatment of these lesions is usually excisional (cold conization, laser conization, diathermic conization) and some studies have pointed the increase of the obstetric complications incidence in these women such as, preterm labor, low birth weight and premature rupture of the membranes in women previously submitted to these treatments. Conservative treatment with intralesional interferon can be among the therapeutical options of patients in fertile age since it does not alter the anatomy of the uterine cervix which is the greatest fact that causes complications during pregnancy. Objectives: Evaluate the clinical response of the patients with Cervical Intraepithelial Neoplasia (CIN) II and III treated with interferon--2b through colposcopy and biopsy; analyze alteration of the immunological parameters, such as cytokines present in the vaginal secretion, before, during and after the treatment, (cytokines IL 1, IL2, IL-4, IL6, IL8, IL-10, IL-12, TNF, INF); verify the presence of high-risk HPV and correlate viral load (before and after the treatment) with the clinical response.Material and Methods: The study group was made up by patients aged 18 to 50 years old, with a diagnosis of high-grade cervical intraepithelial neoplasia, not submitted to previous treatment. In this work it was used Intralesional Human recombinant Interferon--2b 3.000.000 (Blauferon B R-Blausiegel) (18 applications in alternate days).Before the first and at the last application patients were submitted to a colposcopy with the videocolposcopy. Vaginal secretion was collected during the treatment for cytokines analysis, what was done by Cytometric bead array (Flow cytometry 1 BD FACS Calibur TM, protocol suggested by Becton Dickinson (BDTM CBA). Typing HPV was performed by hybrid capture. Results: Initial diagnosis was 62,5% (n=5) of CIN II and 37,5% (n=3) of CIN III. Related to the treatment response: 62,5% (n=5) had response while 37,5% (n=3) had therapeutic failure, with these last ones with lesion occupying more than one quarter. Concentration average of IL-6 (picture 6) showed itself significantly high in the sixth application in the group of patients which had failure compared to the group of the ones who had response in the same application (p=0,357, Mann Whitney Test). Analyzing all the patients (picture 6.1) the range of the average concentration of this interleukin was significant (p=0,0274, Friedmans test). Related to the IL-1β (picture 9), the group of patients who had responses the concentrations continued lower and almost unchanged (p=0,5206, Friedmans test). Average TNF-α concentration (picture 12) was significantly higher in the sixth application in the group that presented therapeutic failure when compared to the group of responses for the same application (p=0,0357, Mann Whitneys test). Comparing the viral load, before and after the treatment in the group of patients who had failure and in the group of those with response (picture 13) it was observed a significant decrease of it in the patients with response (p=0, 0313, Wilcoxons test). Conclusions: High-grade CINs treatment with Intralesional Interferon--2b presented good clinical response in the majority of the patients. IL-6 and TNF-α concentration in the vaginal secretion, during the treatment, is higher in the group of patients that presented therapeutic failure when compared to the group that had response. TNF-α average concentration was significantly higher in the sixth application in the group that presented therapeutic failure when compared to the group with responses in the same application. There is a significant decrease of the high-grade HPV viral load in the patients with therapeutic responses.

ASSUNTO(S)

interferon cervix uteri imunoterapia colo do útero interferon anatomia patologica e patologia clinica immunotherapy

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