P16INK4A Immunohistochemistry as a Gold Standard for Cervical Cancer and Precursor Lesions Screening (original) (raw)
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Evaluation of P16INK4A as a Biomarker in Cervical Intraepithelial Neoplasia
2015
Introduction: Cervical screening would benefit from a test based on a disease-specific biomarker that identifies high grade lesions, which could also indicate the presence of early precancerous lesions that have a high risk of progression to cancer. One such potential biomarker is p16INK4A. Objective of the study was to study the biomarker p16INK4A expression by immunostaining in cervical intraepithelial neoplasia. Material and method: Experimental study conducted from November 2009 to April 2011. 1500 women were screened for cancer cervix using conventional Pap test, VIA and VILI. Women having positive results underwent colposcopy and biopsy if required. P16INK4A expression in biopsy samples was studied using immunohistochemistry. Results: All test positive cases n= 235, underwent colposcopy. Colposcopic abnormalities were detected in n=83 and biopsy proven cervical intraepithelial neoplasia(CIN) in n=15. P16INK4A expression was seen in eight of 15 CIN cases. The strength of positi...
… -Research and Practice, 2006
An immunohistochemical analysis with monoclonal antibody p16 INK4a was performed in formalin-fixed, paraffinembedded samples of 60 cases. The aim was to investigate in biopsies the expression of p16 INK4a of normal uterine cervical tissue, pre-cancerous and cancerous lesions, and their relation with human papilloma virus (HPV) and HIV status. Three parameters were evaluated: percentage of p16 INK4a positive cells, reaction intensity, and cell staining pattern. All of these parameters were statistically different when compared among different histological groups. However, logistic regression model showed that the reaction intensity was the best indicator of the expression of p16 INK4a . This expression increases from normal to invasive squamous carcinoma. Sixty-six percent of the patients with CIN grade 1 (CIN1) expressed p16 INK4a (all these cases were infected with high risk HPV). Our study supports the hypothesis that p16 INK4a expression in pre-cancerous lesions and cancers can be used to identify HPV-transformed cells. Of great interest for routine diagnostic use is the fact that immunohistochemical testing for p16 INK4a seems to be capable of identifying HPV-positive cells and potentially recognizing those lesions with an increased risk of progression to high-grade lesions.
European Journal of Cancer, 2006
A total of 91 cervical archival biopsy series were analysed for the presence and viral load of 'high-risk' types of human papillomavirus (HR-HPV), and p16(INK4a) expression. The women had various degrees of CIN (cervical intraepithelial neoplasia). HPV 16 was the most prevalent type found, at 47% frequency. The frequency of HPV 16 increased with increasing immunoreactivity to p16(INK4a), from 39% to 44% at cases scored low to medium, to 65% at high reactivity. Thirty (33%) of the samples had negative p16(INK4a) analysis results, but were positive for HR-HPV. There was no significant correlation between viral load and the level of p16(INK4a) expression, while the grade of CIN correlated to such expressions. Thus, p16(INK4a) expression analysis yielded information which is consistent with results from the histopathology and might complement the HPV analysis in a clinical prognostic procedure in order to find women at risk for cervical cancer.
Evaluation of p16INK4a Overexpression in a Large Series of Cervical Carcinomas
International Journal of Gynecological Pathology, 2014
The aims of this study were to assess the overexpression of p16 INK4a in formalin-fixed paraffin-embedded cervical carcinoma tissue blocks and to determine its concordance with the human papillomavirus (HPV) status using the SPF 10-LiPA 25 polymerase chain reaction System and its correlation with the histologic type of invasive cervical cancer (ICC) and individual HPV genotypes. A total of 205 retrospectively collected ICC cases were analyzed by p16 INK4a immunohistochemistry. HPV detection was performed by polymerase chain reaction using SPF10 broad-spectrum primers, followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse hybridization line probe assay (LiPA 25). Of 205, 188 analyzed (91.7%) ICC cases showed p16 INK4a overexpression, whereas 181 (83.3%) cases were HPV positive using HPV LiPA testing. One hundred and seventy four (84.9%) cases were both p16 INK4a and HPV LiPA positive, indicating a positive concordance of 89.9% between both techniques (k index agreement of 0.43; Po0.001), and no statistically significant difference (McNemar test, P40.05). Squamous cell carcinomas were strongly positive compared with the adenocarcinomas (93.6% vs. 75% of the cases, respectively). When performed on formalin-fixed paraffin-embedded cervical tissue specimens, the higher positivity rate of p16 INK4a immunohistochemistry as compared with HPV DNA testing may allow identifying HPV-related ICC cases in which HPV testing was negative. Key Words: p16 INK4a-HPV-Cervical cancer-SPF 10-LiPA 25 PCR.
European Scientific Journal, ESJ, 2015
Introduction :The overexpression of p16INK4a is considered to be strong and consistent in HPV-induced cancers. The objective of this study was to investigate the presence of HPV DNA in cervical biopsies, and to study the overexpression of p16INK4a as a marker of precancerous and cancerous lesions of the cervix. Material and methods :A total of 75 cervical biopsies were included in this study involving cervicitis (n = 11), mild dysplasia (n = 17), severe dysplasia (n = 30) and invasive carcinomas (n = 17). The presence of HPV was assessed using an examination in situ hybridization (CSA). p16INK4a protein expression was investigated by immunohistochemistry. Results: p16INK4a expression was very low in benign cervical lesions, while 18.8% of these lesions showed positivity for HPV DNA detection. Forty seven percent of mild dysplastic lesions presented overexpression of p16INK4a protein, and 76.4% were HPV positive. Strong signal of p16INK4a was observed in 100% of severe dysplastic les...
Cureus
Introduction Cervical cancer is the fourth most frequent cancer in women worldwide, and it continues to be a big issue in developing countries. The current case-control study sought to determine the presence of high-risk human papillomaviruses (hr-HPV) in the development of cervical cancer, as well as their relationship with the cell cycle inhibitor gene p16INK4A in cervical cancer. Methods The association between p16INK4A protein and the presence of hr-HPV DNA in cervical lesions was explored in this study, which included 150 cervical cancer patients and 100 normal cervix samples. The immunohistochemistry approach was used to identify the expression of the p16INK4A protein, while the semi-quantitative polymerized chain reaction (PCR) method was used to identify the genomic identity of hr-HPV. Results About 90.67% (n=136) of the 150 case samples were found to be hr-HPV positive. Within the 136 HPVpositive samples, 45 (33.08%) show moderate expression of the p16INK4A protein, whereas 91 (66.91%) show overexpression, which is statistically significant (0.05). Among the 136 HPV-positive samples, 22.08% (N=30) were classified as having cervical intraepithelial neoplasia (CIN), with 56.66% (n=17) having CIN3, 36.66% (n=11) having CIN2, and 6.67% (n=2) having CIN1. Conclusion Based on the semi-quantitative immune staining scoring method of p16INK4A protein, genomic expression of HPV demonstrates that the expression of p16INK4A protein increases with the infectious load of the hr-HPV genome in the host cell. The result directly shows that immunostaining of the p16INK4A protein, in conjunction with the assessment of high-risk HPV in the host genome, will aid in the identification of cervical cancer in the cervix.
Modern Pathology, 2006
The p16 INK4a is a cyclin-dependent kinase inhibitor that decelerates the cell cycle by inactivating the cyclindependent kinases involved in the phosphorylation of the retinoblastoma protein (RB). Expression of E6 and E7 oncogenes of high-risk (HR) human papillomavirus (HPV), affecting the RB-p16 pathway, leads to p16 upregulation. Although it is widely reported that p16 is overexpressed in a high percentage of preneoplastic lesions and in almost all carcinomas of the uterine cervix, protein upregulation and its correlation with HPV infection in low-grade lesions is still being debated. In this study, we investigated in parallel, p16 expression and HPV infection in 100 cervical biopsies (17 normal tissues, 54 CIN1, 10 CIN2, 11 CIN3, eight invasive squamous cancers). Results obtained demonstrated that none of the 17 normal cervical tissues, evaluated by immunohistochemistry, presented p16 positivity whereas, starting from CIN1 (31%) to CIN2 (90%), CIN3 (100%) and carcinomas (100%), a constant and significant increase of protein overexpression (Po0.0001) was observed. In addition, p16 overexpression consistently showed elevated sensitivity (84%) and specificity (98%) in detecting HR-HPV infection with a high positive predictive value (97%) and negative predictive value (86%). Of interest, 93% of the p16-positive CIN1 were also HR-HPV infected. Our findings confirmed that p16 overexpression is associated to high-grade precancerous lesions and cervical carcinomas, and further demonstrated that immunohistochemical evaluation of p16 may be a useful biomarker in identifying HR-HPVinfected low-grade lesions.
Asian Pacific journal of cancer prevention : APJCP, 2017
p16INK4a is a tumor-suppressor protein and cyclin-dependent kinase (cdk) inhibitor that blocks cdk4- and cdk6-mediated pRb phosphorylation to inhibit E2F-dependent transcription and cell-cycle progression. Because the E7 protein of high-risk HPVs inactivates pRB, the resulting overexpression of p16INK4a may be a good marker for infection with high risk HPV types. Immunostaining of p16INK4a allows precise identification of even small CIN or cervical cancer lesions in biopsy sections and can help reduce inter-observer variation in the histopathological interpretation of cervical biopsy specimens. The aims of the present study were to evaluate the expression of p16 INK4a in cervical biopsies and to compare the grade of cervical neoplasia with intensity of staining. The study covered 110 cervical biopsy tissue blocks over a period of 2 years, (85 cases of CIN of varying grade and invasive cervical cancers and 25 of non-neoplastic lesions). Immunostaining with p16INK4a antibodies followe...
Advances in Anatomic Pathology, 2006
p16 INK4a has emerged as a valuable surrogate marker for high-risk human papillomavirus infection and shows increased immunoexpression with worsening grades of cervical intraepithelial neoplasia (CIN). Numerous studies have emerged in recent years supporting its role in the detection of high-grade dysplasia and have lead to the use of p16 INK4a immunohistochemistry in many laboratories. However, only a few studies have examined the possible predictive or prognostic value of p16 INK4a in CIN or cervical cancer. This review addresses some of the practical issues in the application of p16 INK4a in everyday practice, with an emphasis on integrating the extensive data that have emerged in the literature on p16 INK4a immunoreactivity in CIN. The potential role of p16 INK4a immunohistochemistry in the prediction of CIN progression is also discussed.
Human papillomavirus detection and p16INK4a expression in cervical lesions: a comparative study
Human Pathology, 2014
p16 INK4a expression in dysplastic cervical lesions is related to high-risk human papillomavirus (HR-HPV) infection. The immunohistochemical expression of this protein in these lesions allows an increase in diagnostic reproducibility in biopsies and the introduction of prognostic factors in low-grade lesions. Here, we studied the immunohistochemical expression of p16 in 86 dysplastic cervical lesions, 54 cervical intraepithelial neoplasms-grade 1 (CIN-I), 23 CIN-II, and 9 CIN-III. In addition, we performed HPV detection and genotyping. We detected HR-HPV in 19/54 CIN-I, 21/23 CIN-II and 9/9 CIN-III cases. p16 INK4a immunoreactivity was observed in 7/19 CIN-I HR-HPVpositive, 17/21 CIN-II HR-HPV-positive and all CIN-III cases. Immunoreactivity for p16 INK4a was found in 7/54 CIN-I and in 17/23 CIN-II cases. In the follow-up, we detected 3 p16-positive high-grade squamous epithelial lesions (CIN-II and CIN-III) in the CIN-I/p16-negative group and 5 p16-positive high-grade squamous epithelial lesions cases in the CIN-II/p16-negative group. We conclude that p16 negativity in CIN-I and CIN-II biopsies does not always imply regression of the lesion and that the diagnosis of CIN-II should not be based solely on p16 results.