RESUMO
OBJECTIVE: To study the performance values of a set of five immunohistochemical markers involved in cell cycle regulation as a potential aid in the differential diagnosis between squamous intraepithelial lesions (SILs) and normal or benign conditions of the uterine cervix. STUDY DESIGN: Results from immunohistochemical evaluation of p16, cyclin D1, p53, Ki67, and ProEx C markers and human papillomavirus genotyping were collected from a previous study performed on 37 normal or benign cervices, 39 low grade SILs and 73 high grade SILs. A multivariate analysis was used to examine the specific diagnostic value of each marker and to ascertain those most relevant for SIL diagnosis. For markers with good data fit, sensitivity, specificity, accuracy, area under the receiver operating characteristic curve, and integrated discrimination improvement, were calculated. RESULTS: Among individual markers, ProEx C showed the best specificity; p16 displayed the highest sensitivity and area under receiver operating characteristic curve for SIL diagnosis. Integrated discrimination improvement demonstrated that the p16 plus ProEx C model has better discrimination capacity than p16 plus Ki67 or ProEx C plus Ki67. CONCLUSION: Use of ProEx C alone or in combination with p16 could provide useful information for SIL diagnosis.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Proteínas de Ciclo Celular/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Proteínas Nucleares/genética , Papillomaviridae/genética , Neoplasias do Colo do Útero/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Genótipo , Humanos , Imuno-Histoquímica , Componente 2 do Complexo de Manutenção de Minicromossomo , Proteínas Nucleares/metabolismo , Papillomaviridae/isolamento & purificação , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/metabolismoRESUMO
BACKGROUND: Human Papillomavirus (HPV) genotype distribution and co-infection occurrence was studied in cervical cytologic specimens from Murcia Region, (southeast Spain), to obtain information regarding the possible effect of the ongoing vaccination campaign against HPV16 and HPV18. METHODS: A total of 458 cytologic specimens were obtained from two outpatient gynecological clinics. These included 288 normal benign (N/B) specimens, 56 atypical squamous cell of undetermined significance (ASC-US), 75 low-grade squamous intraepithelial lesions (LSIL) and 39 high-grade squamous intraepithelial lesions (HSIL). HPV genotyping was performed using PCR and tube array hybridization. RESULTS: The most frequent genotype found was HPV16 (14.9% in N/B; 17.9% in ASC-US; 29.3% in LSIL and 33.3% HSIL). Distribution of other genotypes was heavily dependent on the cytologic diagnoses. Co-infections were found in 15.3% of N/B, 10.7% of ASC-US, 48% of LSIL and 25.6% of HSIL cases (significantly different at p < 0.001). Strikingly, in N/B diagnoses, genotypes from A5 species were found as coinfecting in all cases. Genotypes from A7 or A9 species appeared in co-infections in 56.5% and 54% respectively whereas genotypes from A6 species appeared in 25.1% of cases. CONCLUSION: HPV vaccination might prevent 34.6% and 35.8% of LSIL and HSIL, respectively. Co-infection rate is dependent on both cytologic diagnosis and HPV genotype. Moreover, genotypes belonging to A5, A7 and A9 species are more often found as co-infections than genotype pertaining to A6 species. This suggests that phylogenetically related genotypes might have in common similar grades of dependency for cervical epithelium colonization.
