Implications of continued upregulation of p16INK4a evolution from high-grade squamous intraepithelial lesion to invasive squamous carcinoma of the cervix

On integration into the host cervical keratinocyte genome, human papillomavirus (HPV) E7 protein binds pRB, releasing E2F from normally incompetent pRB-E2F complexes and allowing propagation of G1-S transition by the E2F. p16 INK4a, a tumour suppressor protein, increases in refl ex response to counter this. 29 histologically re-confi rmed low-grade squamous intraepithelial lesions (LSIL), 27 high-grade squamous intraepithelial lesions (HSIL) and 30 invasive cervical squamous carcinoma (SCC) were immunohistochemically stained for p16INK4a expression using the CINtec Histology Kit (REF 9511, mtm laboratories AG, Heidelberg, Germany) to re-affi rm the notion that integration of HPV occurs predominantly in SCC and possibly HSIL and less in LSIL and normal squamous epithelium (NSqE). Implicit was also the attempt to understand the role of E2F, as indicated by p16INK4a, in evolution of SCC from HSIL. No ethnic predilection was noted for LSIL, HSIL or SCC. Patients with SCC were signifi cantly older by about 14-years compared with HSIL (p<0.05) while there was no signifi cant age difference between HSIL and LSIL. p16INK4a expression was signifi cantly increased (p<0.05) in both HSIL (88.9%) and SCC (83.3%) compared with LSIL (3.4%) and NSqE (0%); the NSqE being normal squamous epithelium noted in 17 of the LSIL, 19 HSIL and 5 SCC. From these fi ndings there is suggestion that fundamental upstream events viz HPV integration, E7 upregulation followed by E2F activation occurs at point of transformation to HSIL and continues unrelentingly for another one to two decades before hitherto unclear factors convert a non-invasive lesion into an overtly invasive malignant counterpart. Interestingly, the occurrence of HSIL and LSIL in almost the same age group could mean that alteration from episomal to integrated form of HPV may not incur a prolonged incubation period, unlike from HSIL to SCC

Detección del virus papiloma humano: influencia del tipo de muestra y la severidad de la lesión intraepitelial cervical / Detection of human papillomavirus: the influence os sample type and severity od cervical intraepithelial lesion

Identificar la influencia del tipo de muestra y la severidad de la lesión, en la detección del ácido desoxirribonucleico del virus papiloma humano mediante reacción en cadena de polimerasa. Entre octubre 2008 y enero 2009, se seleccionaron 68 pacientes con diagnóstico histológico de lesión intraepitelial. Se realizó la detección del ácido desoxirribonucleico de virus papiloma humano a través de reacción en cadena de polimerasa, en muestra citológica e histológica de cuello uterino. Se analizaron los resultados agrupados según tipo de muestra (citológica o histológica) y tipo de lesión intraepitelial (alto o bajo grado). Servicio de Ginecología de la Maternidad "Concepción Palacios" La sensibilidad de la reacción en cadena de polimerasa para la detección del ácido desoxirribonucleico del virus papiloma humano en muestra histológica fue 92,98 por ciento, mayor que la citológica 72,06 por ciento (P < 0,05). La severidad de la lesión no afectó la capacidad global de detección de la prueba (P > 0,05). En lesiones de bajo grado la sensibilidad del extendido fue de 65 por ciento y la de la biopsia fue de 97,2 por ciento; mientras que en las lesiones de alto grado fue de 82,14 por ciento (extendidos) y 85,71 por ciento (biopsias). La severidad de la lesión intraepitelial (alto o bajo grado) no afecta la eficacia de la prueba para detectar el ácido desoxirribonucleico del virus papiloma humano. La detección fue más efectiva en muestras histológicas que en citológicas

Identify the influence of the kind of sample and the severity of the injury, to detect the desoxyribonucleic acid of the human papilloma virus using polymerase chain reaction. Between October 2008 and January 2009, 68 patients with histological diagnosis of intraepithelial lesion were selected, making detection of human papilloma virus desoxyribonucleic acid in polymerase chain reaction, in both, histological and cytological cervical sample. Analysed the results grouped by type specimen (cytological and/or histological) and type of lesion (high or low grade). Service of Gynecology of the Maternidad "Concepcion Palacios", The sensitivity of the polymerase chain reaction for the detection of human papilloma virus desoxyribonucleic acid in histological sample was 92.98 percent, higher than the cytological 72.06 percent (P < 0.05). The severity of the lesions didn’t afect the detection capability of polymerase chain reaction. (P>0.05). The sensitivity of the extended in low grade lesions was 65 percent and the biopsy was 97.2 percent; while in high-grade lesions was 82.14 percent (extended) and 85.71 percent (biopsies). The severity of intraepithelial lesion (high or low grade) does not affect the effectiveness to detect human papilloma virus desoxyribonucleic acid. Detection was more effective in histological samples than in cytological