Although several studies have evaluated the role of p16INK4a as a diagnostic marker of cervical intraepithelial neoplasia (CIN) and its association with disease progression, studies regarding the role of p16INK4a in human immunodeficiency virus (HIV)-infected patients remain scarce. The present study was designed to determine the potential utility of p16INK4a as a diagnostic marker for CIN and invasive cervical cancer in HIV-positive and negative cervical specimens. An immunohistochemical analysis of p16INK4a was performed in 326 cervical tissue microarray specimens. Performance indicators were calculated and compared using receiving operating characteristics curve (ROC)/area under the curve. In HIV-1-negative women, the percentage of cells that was positive for p16INK4a expression was significantly correlated with the severity of CIN (p < 0.0001). A ROC curve with a cut-off value of 55.28% resulted in a sensitivity of 89%, a specificity of 81%, a positive predictive value of 91% and a negative predictive value of 78%. HIV-seropositive women exhibited decreased expression of p16INK4a in CIN2-3 specimens compared with HIV-negative specimens (p = 0.031). The ROC data underscore the potential utility of p16INK4a under defined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. HIV-1 infection, however, is associated with relatively reduced p16INK4a expression in CIN 2-3.

INTRODUÇÃO: O câncer de colo uterino é um grave problema de saúde pública no Brasil. Em pacientes com colpocitologias sugestivas de lesão intra-epitelial escamosa de alto grau (HSIL) e colposcopia insatisfatória sem lesão visível, a recomendação nacional é repetir a colpocitologia após três meses. Nosso objetivo foi medir a prevalência de HSIL e câncer em pacientes com a primeira colpocitologia sugestiva de HSIL e colposcopia insatisfatória sem lesão visível, no intuito de contribuir para a discussão sobre uma conduta clínica mais efetiva e que diminua a probabilidade de perdas de acompanhamento antes do diagnóstico e tratamento adequados. TIPO DE ESTUDO E LOCAL: Estudo transversal no Ambulatório de Colposcopia do IFF/Fiocruz. MÉTODO: Pacientes recebidas no período de dezembro de 1989 a abril de 2007 com diagnóstico citológico de HSIL sem lesão visível em colposcopias insatisfatórias foram submetidas a conização do colo uterino. RESULTADOS: Foram incluídas 65 pacientes na situação descrita e encontrados 33,8% de HSIL e 4,6% de câncer confirmados histologicamente. Os demais casos apresentaram lesão intra-epitelial escamosa de baixo grau (26,1%), displasia glandular (1,5%) e ausência de doença (33,8%). CONCLUSÃO: A prevalência de HSIL ou câncer encontrada não parece suficiente para defender a conduta de encaminhar as pacientes de imediato para conização a fim de investigar o canal cervical. Os achados sugerem que a recomendação de repetir a citologia após uma primeira com HSIL sem lesão visível e colposcopia insatisfatória é apropriada no nosso cenário. Devem ser implementados esforços para adesão às recomendações de acompanhamento e reduzir a chance de perdas.

CONTEXT AND OBJECTIVE: Cervical cancer is a serious public health problem in Brazil. For patients with unsatisfactory colposcopic examinations without visible lesions, but with cervical cytological tests suggesting high-grade squamous intraepithelial lesion (HSIL), the national recommendation is to repeat cervical cytological tests after three months. Our aim was to assess the prevalence of HSIL and cancer among patients with initial cervical cytological tests suggestive of HSIL but with unsatisfactory colposcopic examinations without visible lesions, in order to contribute towards the discussion regarding a more effective clinical approach that might diminish the likelihood of patient abandonment of follow-up before appropriate diagnosis and treatment. DESIGN AND SETTING: Cross-sectional study in Colposcopy Clinic of IFF/Fiocruz. METHOD: Patients admitted between December 1989 and April 2007 with cytological diagnoses of HSIL but with unsatisfactory colposcopic examinations without visible lesions underwent cervical cone biopsy. RESULTS: Sixty-five such patients were included, comprising 33.8% with HSIL and 4.6% with cancer, confirmed histologically. The other patients presented low-grade squamous intraepithelial lesion (26.1%), glandular dysplasia (1.5%) and absence of disease (33.8%). CONCLUSION: The observed prevalence of cancer and HSIL does not seem to be enough to justify immediate referral for cone biopsies to investigate the cervical canal in these cases. The findings suggest that the recommendation of repeated cytological tests following an initial one with HSIL, among patients with unsatisfactory colposcopic examinations without visible lesions, is appropriate in our setting. Efforts are needed to ensure adherence to follow-up protocols in order to reduce the chances of losses.