Análise multimodal da citologia, colposcopia, teste do HPV e DNA-ICM no prognóstico da neoplasia intraepitelial cervical

Abstract

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Médicas, Florianópolis, 2020.Introdução: o tratamento da lesão precursora diminui a incidência de câncer do colo uterino, mas, em contrapartida, aumenta riscos obstétricos, ansiedade e custos. O arsenal diagnóstico existente não oportuniza o prognóstico da neoplasia intraepitelial cervical (NIC). Objetivo: avaliar o papel da aneuploidia como biomarcador de lesão de pior evolução em conjunto com o perfil epidemiológico e comparar a sensibilidade e a especificidade dos achados de citometria do DNA com os de outros métodos diagnósticos e os destes entre si. Método: estudoobservacional prospectivo de coorte contendo 254 mulheres com colpocitologia alterada.Coleta citológica em solução ThinPrep® PreservCyt® dessas pacientes foram realizadas para execução de citometria de DNA e pesquisa de HPV, além de colposcopia com biópsia quando indicada. Após a aplicação da conduta adequada, observacional ou cirúrgica, as participantes foram avaliadas a cada seis meses e a coorte dividida em dois grupos, conforme o comportamento da doença. No grupo ?casos? foram incluídas pacientes com: progressão da NIC; recidiva de NIC 2+ após EZT; persistência de NIC 1, durante 2 anos; e as com menos de 25 anos com NIC 2 que se manteve ou evoluiu. No grupo ?não casos?, aquelas com: examesnormais; alteração de baixo grau na citologia sem correspondência na colposcopia; e NIC 1 não persistente. A regressão logística e o modelo multivariado de COX foram utilizados para identificação dos fatores de risco independentes para diagnóstico e prognóstico de NIC de alto grau e curva ROC para avaliar sensibilidade e especificidade dos métodos. Resultados: a coorte foi composta por 153 mulheres, pois 82 participantes não compareceram ao retorno e 19 tiveram diagnóstico de câncer no atendimento inicial. A análise dos resultados demonstrou: que asvariáveis ?idade maior ou igual a 30 anos? (OR=3,6), ?tamanho da lesão maior que 20%? (OR=6,49), ?aneuploidia? (OR=12,04) e ?HPV 16? (OR=7,47) tiveram associação com o diagnóstico de NIC 2+ (pAbstract: Introduction: treatment of precursor lesion decreases the incidence of cervical cancer, but, on the other hand, increases obstetric risks, anxiety and costs. The existing diagnostic arsenal does not provide an opportunity for prognosis of cervical intraepithelial neoplasia (CIN). Objective: to assess the role of aneuploidy as a biomarker of the worst-evolving lesion in conjunction with epidemiological profile and to compare sensitivity and specificity of DNA cytometry results with those of other diagnostic methods and those of each other. Method: prospective observational cohort study with 254 women with altered colpocytology. Colpocytological collection in ThinPrep® PreservCyt® solution from these patients was performed to perform DNA cytometry and HPV research, in addition to colposcopy with biopsy when indicated. After applying the appropriate conduct, observational or surgical, participants were evaluated every six months and the cohort divided into two groups, according to the disease's behavior. The ?cases? group included patients with: progression of CIN; recurrence of CIN 2+ after EZT; persistence of CIN 1 for 2 years; and those under 25 years old with CIN 2 that remained or evolved. In the ?non-cases? group, those with: normal exams; low-grade change in cytology with no match in colposcopy; and non-persistent CIN 1. Logistic regression and multivariate COX model were used to identify the independent risk factors for diagnosis and prognosis of high-grade CIN, and ROC curve to assess sensitivity and specificity of the methods. Results: the cohort consisted of 153 women, as 82 participants did not attend the return visit and 19 were diagnosed with cancer at the initial visit. The analysis of the results showed: that the variables ?age greater than or equal to 30 years? (OR = 3.6), ?lesion size greater than 20%? (OR = 6.49), ?aneuploidy? (OR = 12 , 04) and ?HPV 16? (OR = 7.47) were associated with the diagnosis of CIN 2+ (p <0.05) and ?aneuploidy? (HR = 4.34) and ?having HIV? (HR = 6.47) (p <0.05) with lesions with a worse prognosis; and that the strength of agreement (p <0.001) for colposcopy, using Kappa test, was good, with a sensitivity of 79.3% (95% CI, 71.0-85.6) and specificity of 94.4% ( 95% CI, 88.3-97.4); DNA cytometry and oncotic cytology, moderate (p <0.001), respectively with sensitivity of 74.6% (95% CI, 66.2-81.4) and 72.3% (95% CI, 63.9 -79.4) and specificity of 85.3% (95% CI, 77.4-90.7) and 76.1% (95% CI, 67.3-83.1); and high-risk HPV and HPV 16 tests, weak, with sensitivity of 75.0% (95% CI, 63.1-84.0) and 43.75% (95% CI, 32.2-55, 9) and specificity of 50.0% (95% CI, 35.8-64.1) and 88.64% (95% CI, 76.0-95.0). Conclusion: research results indicate that detection of aneuploidy by DNA-ICM, a painless and non-invasive method, is promising for prediction of more severe cervical lesions, as well as the fact of having HI