Perfil de citocinas no soro e na secreção cervical de mulheres com lesão intraepitelial de baixo grau, lesão intraepitelial de alto grau e carcinoma epidermóide invasor.

Introduction: Infection with oncogenic types of human papillomavirus (HPV) is the most important factor for development of intraepithelial lesions and invasive squamous cell carcinoma. The immune response has an important role in the natural history of HPV infection in uterine cervix is involved in viral persistence and progression of lesions. Cytokines are molecules that regulate the transcription of HPV; the Th1 cytokine profile contributes to the development of cellular immunity against HPV infection and neoplasia, and is related to clearance of infection. The Th2 cytokine profile is associated with persistence of viral infection and the progression of lesions. Objectve: To evaluate the concentration of IL-2, IL-4, IL-6, IL10, IL-12, IFN-γ and TNF-α in cervical secretion and serum of women with low-grade squamous intraepithelial lesions (LSIL), high-grade intraepithelial lesion (HSIL) and invasive squamous cell carcinoma (EC). Patients and Methods: The study included 109 women with histological diagnosis of LSIL (n = 16), HSIL (n = 40), EC (n = 13) and 40 women with suspected of HPVinduced disease, but no pathological changes on cervix biopsy (control group) attending in the Colposcopy Clinic of the Botucatu Medical School (UNESP) and in the Preventive Gynecology, Hospital Amaral Carvalho, Jau, SP. During speculum examination cervical secretion was collected with cytobrush to determining the profile of cytokines. The peripheral blood of women enrolled in the study was collected by venipuncture in 10 mL volume and patterns of cytokines in serum and cervical secretion were assessed by enzyme immunoassay (ELISA). The search for HPV in the fragments of the biopsies were performed using the technique of polymerase chain reaction (PCR) using specific primers (MY9/11 and GP5+/GP6+) and genotyping was performed using the technique of PCR primers specific and confirmed by the analysis of restriction fragment polymorphism technique (RFLP). The socio-demographic and gynecological were obtained by interview at enrollment of patients in the study. Results: Regarding the characteristics of the patients, 78.9% were white, 60.5% reported stable, 23.8% completed the second degree, 37.6% were smokers, 57.8% had at least three sexual partners lifetime, 8.3% reported a history of previous STD and 36.7% used oral contraceptives. The median age of patients was significantly higher in EC compared to other groups. HPV DNA was detected in 90% of samples from the control group, 93.7% in LSIL, 100% in HSIL and 84.6% in the EC. The HPV type 16 was the prevalent in all studied groups. The levels of IL-4, IL-6 and IL-10 in cervical secretion were significantly increased in patients with EC when compared with control groups, LSIL and HSIL. In the serum, the level of IL-6 was significantly increased in patients with HSIL. Conclusion: These results corroborate the finding that the increase of Th2 cytokines in serum and cervical secretion of women with HSIL and EC is related to the progression of intraepithelial lesions.