1. p16INK4a immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis
- Author
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N. Wentzensen, Maria Kyrgiou, Evangelos Paraskevaidis, George Koliopoulos, I. Tsoumpou, Marc Arbyn, Pierre Martin-Hirsch, and Vasiliki Malamou-Mitsi
- Subjects
Biopsy ,Cyclin-Dependent Kinase Inhibitor p16/*analysis ,Uterine Cervical Neoplasms ,Uterine Cervical Dysplasia/metabolism/virology ,Neoplasm Proteins/analysis ,Cervix Uteri ,Alphapapillomavirus ,Uterine Cervical Dysplasia ,Prospective Studies ,Colposcopy ,medicine.diagnostic_test ,Uterine Cervical Neoplasms/*chemistry/diagnosis/virology ,Cytological Techniques/utilization ,Histological Techniques ,General Medicine ,Immunohistochemistry ,Neoplasm Proteins ,medicine.anatomical_structure ,Oncology ,Research Design ,Biomarker (medicine) ,Female ,medicine.medical_specialty ,Cytological Techniques ,Cervix Uteri/*chemistry/pathology/virology ,Cervical intraepithelial neoplasia ,Immunohistochemistry/utilization ,Article ,Predictive Value of Tests ,Histological Techniques/utilization ,medicine ,Biomarkers, Tumor ,Humans ,Radiology, Nuclear Medicine and imaging ,Cervix ,Cyclin-Dependent Kinase Inhibitor p16 ,Retrospective Studies ,Gynecology ,Vaginal Smears ,Tumor Markers, Biological/analysis ,business.industry ,Papillomavirus Infections ,Histology ,medicine.disease ,Uterine Cervicitis/*diagnosis/metabolism ,Uterine Cervicitis ,Papillomavirus Infections/*diagnosis/metabolism ,Biological Markers/analysis ,business ,Ascus ,Cervical Intraepithelial Neoplasia/chemistry/diagnosis ,Biomarkers - Abstract
BACKGROUND: P16(INK4a) is a biomarker for transforming HPV infections that could act as an adjunct to current cytological and histological assessment of cervical smears and biopsies, allowing the identification of those women with ambiguous results that require referral to colposcopy and potentially treatment. MATERIAL AND METHODS: We conducted a systematic review of all studies that evaluated the use of p16(INK4a) in cytological or histological specimens from the uterine cervix. We also estimated the mean proportion of samples that were positive for p16(INK4a) in cytology and histology, stratified by the grade of the lesion. RESULTS: Sixty-one studies were included. The proportion of cervical smears overexpressing p16(INK4a) increased with the severity of cytological abnormality. Among normal smears, only 12% (95% CI: 7-17%) were positive for the biomarker compared to 45% of ASCUS and LSIL (95% CI: 35-54% and 37-57%, respectively) and 89% of HSIL smears (95% CI: 84-95%). Similarly, in histology only 2% of normal biopsies (95% CI: 0.4-30%) and 38% of CIN1 (95% CI: 23-53%) showed diffuse staining for p16(INK4a) compared to 68% of CIN2 (95% CI: 44-92%) and 82% of CIN3 (95% CI: 72-92%). CONCLUSION: Although there is good evidence that p16(INK4a) immunostaining correlates with the severity of cytological/histological abnormalities, the reproducibility is limited due to insufficiently standardized interpretation of the immunostaining. Therefore, a consensus needs to be reached regarding the evaluation of p16(INK4a) staining and the biomarker needs to be assessed in various clinical settings addressing specific clinical questions. Cancer Treat Rev
- Published
- 2009