Absence of Nuclear p16 Is a Diagnostic and Independent Prognostic Biomarker in Squamous Cell Carcinoma of the Cervix.

The tumor-suppressor protein p16 is paradoxically overexpressed in cervical cancer (CC). Despite its potential as a biomarker, its clinical value and the reasons for its failure in tumor suppression remain unclear. Our purpose was to determine p16 clinical and biological significance in CC. p16 expression pattern was examined by immunohistochemistry in 78 CC cases (high-grade squamous intraepithelial lesions (HSILs) and squamous cell carcinomas of the cervix -SCCCs). CC cell proliferation and invasion were monitored by real-time cell analysis and Transwell® invasion assay, respectively. Cytoplasmic p16 interactors were identified from immunoprecipitated extracts by liquid chromatography-tandem mass spectrometry, and colocalization was confirmed by double-immunofluorescence. We observed that SCCCs showed significantly more cytoplasmic than nuclear p16 expression than HSILs. Importantly, nuclear p16 absence significantly predicted poor outcome in SCCC patients irrespective of other clinical parameters. Moreover, we demonstrated that cytoplasmic p16 interacted with CDK4 and other unreported proteins, such as BANF1, AKAP8 and AGTRAP, which could sequester p16 to avoid nuclear translocation, and then, impair its anti-tumor function. Our results suggest that the absence of nuclear p16 could be a diagnostic biomarker between HSIL and SCCC, and an independent prognostic biomarker in SCCC; and explain why p16 overexpression fails to stop CC growth.

Prevalencia de virus del papiloma humano en mujeres españolas de un programa de cribado poblacional / Prevalence of human papillomavirus in Spanish women from a population screening program

Introducción. El virus del papiloma humano (VPH), es causa necesaria para el desarrollo de cáncer de cuello uterino. El objetivo del estudio fue estimar la prevalencia de mujeres con infección por VPH, adheridas al Programa de Prevención y Detección precoz de Cáncer de cuello de útero de Castilla y León (España). Material y métodos. Se han evaluado los resultados del análisis de VPH en las muestras de las mujeres incluidas en el programa de cribado poblacional. El estudio incluye un total de 120.326 muestras de frotis de cérvix, recogidas en el periodo comprendido entre enero de 2012 y diciembre de 2014. Resultados. Se obtuvieron 12.183 muestras con detección positiva de ADN de VPH, correspondiendo a una prevalencia de 9,6‰ (IC 95% 9,5%-9,8%), en la población femenina. Los VPH asociados a un alto riesgo de transformación celular se encuentran en mayor proporción que los de bajo riesgo (5,9% vs 2,23%). La prevalencia está inversamente relacionada con la edad de las mujeres del cribado. La presencia de infecciones múltiples de VPH se demuestra en un tercio de las mujeres analizadas. Conclusiones. Estos resultados son los primeros y más amplios de un programa de cribado poblacional estructurado en España y deben servir como referencia para futuros estudios y medir el impacto futuro de la vacunación (AU)

Introduction. The human papillomavirus (HPV), is necessary to cause a woman developing cervical cancer. The aim of the study was to estimate the prevalence of women with HPV infection, covered by the program of prevention and early detection of cervical cancer of Castile and León (Spain). Material and methods. Samples of women included in the screening program were analyzed. Including a total of 120,326 cervical swab samples, collected in the period from January 2012 to December 2014. Results. 12,183 HPV positive samples were detected, representing a prevalence of 9.6 ‰, (IC 95% 9.5%-9.8%) in the female population. High-risk HPV were found in higher proportion that HPV low-risk genotypes. HPV prevalence correlates inversely with women age. Coinfections of multiple genotypes were found in one third of screened women population. Conclusions. Data showed in this study are the first and wider Spanish results from a cervical cancer screening program population non opportunistic based on HPV detection. These results would serve as a reference for future prevalence studies and to evaluate the future impact of HPV vaccination campaigns (AU)