Metilação genética, neoplasia intraepitelial cervical e câncer do colo uterino / Genetics methylation, cervical intraepithelial neoplasia and cervical cancer

O câncer de colo uterino é uma importante causa de morte entre as mulheres em países subdesenvolvidos. A infecção persistente pelo papilomavírus humano (HPV) oncogênico e o comprometimento da resposta imune são fatores de risco para o desenvolvimento da neoplasia intraepitelial cervical (NIC) e sua progressão para o câncer cervical invasivo. O diagnóstico precoce e o tratamento das lesões precursoras do câncer são de grande importância. Estudos epigenéticos estão sendo realizados com o objetivo de avaliar sua influencia nos processos de oncogênese, visto que alterações epigenéticas estão presentes em quase todos os tumores. A metilação de DNA e a acetilação de histonas são as duas mudanças epigenéticas mais estudadas. O melhor entendimento do perfil epigenético na neoplasia intraepitelial cervical e no câncer cervical invasor pode ser utilizado no diagnóstico e prognóstico deste câncer. O objetivo desta revisão consistiu em entender as mudanças epigenéticas encontradas até o momento nas pacientes com NIC e câncer de colo uterino. Foi realizada revisão da literatura de estudos indexados em banco de dados, como PubMed e LILACS. Verificou-se que, até o presente momento, não há um marcador de metilação que tenha o desempenho adequado para servir como indicador para as lesões precursoras do câncer, ou mesmo para o carcinoma cervical.

The cervical cancer is a major cause of death among women in developing countries. Persistent infection by human papillomavirus (HPV) and oncogenic involvement of the immune response are risk factors for the development of cervical intraepithelial neoplasia (CIN) and its progression to invasive cervical cancer. Early diagnosis and treatment of cancer precursor lesions are of great importance. Epigenetic studies are being conducted to evaluate its influence in the process of oncogenesis, since epigenetic alterations are present in almost all tumors. DNA methylation and histone acetylation are the two most studied epigenetic changes. An improved understanding of the epigenetic profile in CIN and invasive cervical cancer can be used in the diagnosis and prognosis of this cancer. The aim of this review was to understand the epigenetic changes found to date in patients with CIN and cervical cancer. We performed a literature review of studies indexed in databases such as PubMed and LILACS. It was found that, to our knowledge, there is no methylation marker with an adequate performance to serve as an indicator for cancer precursor lesions, or even for cervical carcinoma.

Prevalence and risk factors for cervical intraepithelial neoplasia among HIV-infected women

OBJECTIVES: To evaluate the prevalence and the risk factors for cervical intraepithelial neoplasia (CIN) among HIV-infected women. METHODS: Cross-sectional study of 494 HIV-infected women in Brazil, between 1998 and 2008. Gynecologic exam was performed, and samples were collected for cervical cytology and for HPV DNA detection. Cervical biopsy was carried out when indicated. HPV infection, CD4 T-lymphocyte count and HIV viral load were compared with cervical histopathology. Univariate and multivariate statistical analyses were performed to evaluate the statistical association of several risk factors. RESULTS: CIN prevalence detected by histopathology was 23.4% (6% of CIN2/3 and 17.4% cases of CIN1). Multivariate analysis confirmed an independent association of CIN with CD4 T-lymphocyte count below 200 cells/mm³ (OR 5.0, 95% CI 2.5-10.1), with a positive detection of HPV DNA (OR 2.0, 95% CI 1.2-3.5), and with age < 34 years old (OR 1.5, 95% CI 1.0-2.4). HIV viral load and antiretroviral use were not independent risk factors for CIN. CONCLUSIONS: Severity of immunosupression, presence of HPV infection and younger age are strong predictors of CIN among HIV-infected women.