RESUMO
The aim of this study on a series of biopsies diagnosed as normal, metaplastic, low-grade squamous intraepithelial lesions (LSILs), and high-grade squamous intraepithelial lesions (HSILs) was dual: to determine the chronology of cell cycle and proliferation abnormalities after human papillomavirus infection during the development of squamous intraepithelial lesions and to determine the best diagnostic indicator(s) linked to the appearance of an HSIL. Ninety-nine cervical biopsies, 18 normal, 9 with metaplastic changes, 29 LSIL, and 43 HSIL (23 cervical intraepithelial neoplasia 2 and 20 cervical intraepithelial neoplasia 3), were analyzed by image cytometry for DNA ploidy and p16INK4A determination, AgNOR counting, MIB-1, and ICBP90 immunostaining quantification. The human papillomavirus status had been previously determined on corresponding cytological smears with the Hybrid Capture II test. Suspect DNA profile and p16INK4A staining were the first significant events that preceded the increase of cell proliferation. Indeed, these markers were the best tests for the detection of a lesion, whatever its grade (positive predictive values of 90% and 100%, respectively). The presence of MIB-1- or ICBP90-positive cells in the upper two thirds of the epithelium was a very accurate feature to select HSIL (sensitivity, 100% for MIB-1) but with a low specificity. The sensitivity of a suspect DNA profile associated with a positive MIB-1 or ICPB90 immunostaining for the detection of an HSIL was, respectively, 92.8% and 92.7%; their specificities were 54.2% and 44%; their positive predictive values were 78% and 73%; their negative predictive values were 81.2% and 78.6%; and the global values were 78.8% and 74.3%. Thus, the most accurate test to distinguish an LSIL from an HSIL was the association of a suspect DNA profile and the presence of MIB-1- or ICBP90-positive cells in the upper two thirds of the epithelium.
Assuntos
Ciclo Celular , Proliferação de Células , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Anticorpos Antinucleares/metabolismo , Anticorpos Monoclonais/metabolismo , Antígenos Nucleares/análise , Biomarcadores Tumorais , Biópsia , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Distribuição de Qui-Quadrado , Inibidor p16 de Quinase Dependente de Ciclina/análise , Inibidor p16 de Quinase Dependente de Ciclina/genética , Sondas de DNA de HPV/genética , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Proteínas Nucleares/análise , Papillomaviridae/genética , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Ploidias , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Ubiquitina-Proteína Ligases , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/metabolismo , Displasia do Colo do Útero/cirurgia , Displasia do Colo do Útero/virologiaRESUMO
To improve the positive predictive value (PPV) for high-risk human papillomavirus (HR-HPV) in primary screening, DNA ploidy was measured on the same liquid-based sample by image cytometry in 984 cases showing discrepancies between cytology and HR-HPV testing. Of the conflicting results, 14.5% corresponded to a cytologic lesion (from atypical squamous cells of undetermined significance to high-grade squamous intraepithelial lesion [HSIL]) without HPV detected, and 85.5% of smears were within normal limits but revealed an HR-HPV infection. A suspect DNA profile was associated significantly with a lesion. In 497 patients who underwent repeated HPV testing, a normal DNA profile at the first smear predicted the clearance of HPV infection (sensitivity, 81.5%; specificity, 45.4%; PPV, 69%; negative predictive value, 62.4%). In persistent HR-HPV infection, a suspect DNA profile at the first smear increased the PPVfrom 10.8% to 22.7% for the detection of a histologically proven HSIL with a sensitivity of 95.2%. DNA ploidy can be used to select smears with high risk of HSIL, especially in cases of persistent HR-HPV infection.
