Evaluation of p16 Immunostaining to Predict High-Grade Cervical Intraepithelial Neoplasia in Women With Pap Results of Atypical Squamous Cells of Undetermined Significance
ABSTRACT p16 immunostaining has been examined to detect high-grade cervical intraepithelial neoplasia grade (CIN2+) in Pap cytology specimens. However, the utility of p16 in predicting CIN2+ in Pap specimens with atypical squamous cells of undetermined significance (ASC-US) or atypical squamous cells, cannot exclude high-grade squamous intraepithelial neoplasm (ASC-H), is controversial. In this study, we evaluated the utility of p16 immunostaining for predicting CIN2+ in 78 Pap specimens with ASC-US/ASC-H and compared the results in high-risk HPV DNA and the follow-up biopsies. p16 immunostaining was positive in 47% (37/78) of the Pap specimens. Of the 13 Pap specimens with follow-up biopsy results of CIN2+, 7 (54%) were positive for p16. p16 positivity in the Pap specimens was not significantly associated with a CIN2+ biopsy result (P = 0.76). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of p16 immunostaining for predicting CIN2+ were 54%, 52%, 19%, and 85%, respectively. High-risk HPV DNA was detected in 40% (31/78) of the Pap specimens. The sensitivity, specificity, PPV, and NPV of HPV DNA for predicting CIN2+ were 100%, 72%, 42%, and 100%, respectively. High-risk HPV genotypes were detected in six p16-negative specimens with follow-up biopsy results of CIN2+. Our findings suggest that the utility of p16 immunostaining for predicting CIN2+ in Pap specimens with ASC-US/ASC-H is limited. Scant abnormal cells in Pap specimens with ASC-US/ASC-H may have contributed to the low p16 sensitivity. Diagn. Cytopathol., 2011. © 2010 Wiley-Liss, Inc.
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ABSTRACT: The protein capsid L1 of the human papilloma virus (HPV) - a key factor in the cervical carcinogenesis - is considered, together with p16, EGFR and COX-2, a characteristic marker for the evaluation of the malignancy progression and prognostic, in terms of tumoral aggressiveness. The purpose of the present study was to make a comparative assessment between the immunohistochemical pattern of p16, EGFR and COX-2 and immunochemical expression of L1 HPV capsid protein, in low grade and high-grade cervical squamous intraepithelial lesions, in order to determine the relationship of these tumoral markers with the infection status of HPV, and their practical applicability in patients diagnosis and follow-up. The study group included 50 women with cytological and histopathological confirmed LSIL (low grade SIL) and HSIL (high-grade SIL). The immunoexpression of L1 HPV protein was assessed on conventional cervico-vaginal smears and EGFR, COX-2 and p16 were immunohistochemically evaluated on the corresponding cervical biopsies. From all cervical smears, the HPV L1 capsid protein was expressed in 52% of LSIL and 23% of HSIL. From all cervical biopsies, p16 was positive in 64% of LSIL, 82% of CIN2 and 100% of CIN3, EGFR was overexpressed in 67% of HSIL (56% CIN2 and 43% CIN3) and 32% LSIL. For COX-2, the Allred score was higher in HSIL when compared to LSIL. Our data revealed 33 cases belonging to both LSIL and HSIL categories with the same Allred score. Immunochemical detection of L1 capsid protein, on cervico-vaginal smears, indicates an immune status induced by the HPV infection and may offer prognosis information, mainly in LSIL lesions. The assessment of p16, EGFR, and COX-2 allows to an integrative approach for the progression of squamous intraepithelial lesion, associated or not with the HPV infection.Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 01/2011; 52(4):1187-94. · 0.72 Impact Factor
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ABSTRACT: While organized screening programs in industrialized countries have significantly reduced cervical cancer incidence, cytology-based screening has several limitations. Equivocal or mildly abnormal Pap tests require costly retesting or diagnostic work-up by colposcopy and biopsy. In low-resource countries, it has been difficult to establish and sustain cytology-based programs. Advances in understanding human papillomavirus biology and the natural history of human papillomavirus-related precancers and cancers have led to the discovery of a range of novel biomarkers in the past decade. In this article, we will discuss the potential role of new biomarkers for primary screening, triage and diagnosis in high-resource countries and their promise for prevention efforts in resource constrained settings.Future Microbiology 09/2011; 6(9):1083-98. DOI:10.2217/fmb.11.87 · 3.82 Impact Factor
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ABSTRACT: Biomarkers indicating the initiation of neoplastic transformation processes in human papillomavirus (HPV)-infected epithelial cells are moving into the focus of cancer prevention research, particularly for anogenital cancer, including cancer of the uterine cervix. Based on the in-depth understanding of the molecular events leading to neoplastic transformation of HPV-infected human cells, the cyclin-dependent kinase inhibitor p16(INK4a) turned out to be substantially overexpressed in virtually all HPV-transformed cells. This finding opened novel avenues in diagnostic histopathology to substantially improve the diagnostic accuracy of cervical cancer and its precursor lesions. Furthermore, it provides a novel technical platform to substantially improve the accuracy of cytology-based cancer early-detection programs. Here, we review the molecular background and the current evidence for the clinical utility of the p16(INK4a) biomarker for HPV-related cancers, and cervical cancer prevention in particular.Expert Review of Proteomics 04/2012; 9(2):149-63. DOI:10.1586/epr.12.13 · 3.54 Impact Factor