Expression of p16INK4a and human papillomavirus 16 with associated risk factors in cervical premalignant and malignant lesions (original) (raw)
Related papers
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.
Diagnostic Pathology, 2014
Background: Cervical cancer is one of the most common cancers affecting women worldwide. It is well established that human papilloma virus (HPV) infection is the prime risk factor in the development of cervical cancer. The current screening and diagnostic tests have limitations in identifying the range of lesions caused by HPV. The current study aims to evaluate the diagnostic value of p16 immunohistochemical (IHC) investigation in high-risk human papillomavirus (HR-HPV) related lesions of the uterine cervix in Hospital Tuanku Jaafar, Seremban, Malaysia. Methods: A total of 75 cases were selected from the records of Pathology services, Hospital Tuanku Ja'afar, Seremban. The samples were collected in three separate groups (n = 25 per group) as Carcinoma cervix, Carcinoma in situ and Chronic cervicitis. The demographic data of the patients and the representative paraffin blocks were retrieved from Hospital Tuanku Ja'afar, Seremban. The immunohistochemical staining with p16 and HPV 16 L1 were done on all cases. The staining intensity and density were observed and compared among the three groups of cases. Results: Immunohistochemistry of p16INK4A staining shows nil (0/25) expression in the cervicitis patients, 72% (18/25) in CIN patients and 100% (25/25) in cervical carcinoma. HPV 16 L1 was positive in 100% (25/25) of cervicitis patients, 96% (24/25) of CIN patients and 40% (10/25) of cervical cancers patients. A chi square test was used to analyze the result and the obtained p value was <0.05. Conclusion: p16 expression was strongly observed in cervical cancer and minimally observed in cervicitis. Thus indicating p16 immunohistochemistry investigations can aid in diagnosing the different categories of cervical lesions into benign, insitu and malignant.
European Journal of Cancer, 2006
A total of 91 cervical archival biopsy series were analysed for the presence and viral load of &amp;amp;amp;amp;amp;amp;amp;#39;high-risk&amp;amp;amp;amp;amp;amp;amp;#39; 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.
IP innovative publication pvt. ltd, 2019
Introduction: Cervical cancer is the most common cancer in developing country. Early diagnosis of intraepithelial cervical neoplasia and malignancy is important. Infection with Human Papilloma Virus (HPV) results in precancerous lesions and invasive cervical cancer. Interaction of HPV oncogenic proteins with cellular regulatory proteins leads to upregulation of p16INK4a, a cyclin dependent kinase inhibitor. Therefore, p16INK4a overexpression is a surrogate biomarker of HPV infection making it useful in evaluating HPV associated premalignant and malignant lesions of gynecological tract. In our study we have used p16INK4a IHC staining to find out its correlation with dysplasia grading and cervical carcinoma. Materials and Methods: This retrospective descriptive case series for five years duration (from Jan 2014 to Dec2018) was conducted in the Department of Pathology, IGMC & RI, Puducherry, India. A total of 43 cervical biopsies and hysterectomies were collected out of which 17 cases were of carcinoma cervix and 26 cases were of cervical intraepithelial neoplasia ( CIN). All biopsies were subjected to p16INK4a staining. Results: The Immuno expression of p16INK4a of CIN I was 13.3%, CIN II was 20%, CIN III was 50% and Carcinoma cervix was 100%. In normal (non dysplasia) cervical epithelium it showed, 100% negative association. Conclusion: IHC expression of p16INK4a in cervical biopsy is directly related to degree of histological dysplasia and malignancy, so it may be used as a adjunct with routine histopathological examination in identifying cervical dysplasia and also has prognostic value in the management of cervical lesions.
Brazilian Journal of Medical and Biological Research, 2008
The purpose of the present study was to identify the expression of p16 INK4 in cervical cancer precursor lesions by immunohistochemistry and to correlate it with lesion grade and presence of human papillomavirus (HPV) infection. Cervical specimens from 144 women seen consecutively at the gynecology outpatient clinic of our institution from December 2003 to May 2005 were analyzed by cytopathology, histopathology, polymerase chain reaction for HPV-DNA, and p16 INK4 immunostaining. Histologically normal biopsies, HPV-DNA negative by polymerase chain reaction, were used as control. HPV-DNA prevalence, including the control group, was 68.1% and the prevalence of p16 INK4 expression was 55.0%. The percentage of cells stained by p16 INK4 ranged from 10 to 100%, both in the group consisting of cervical intraepithelial neoplasia (CIN)1/HPV specimens and in the group of CIN2/CIN3 specimens with P value of 0.0001. p16 INK4 expression was 48.3% in the CIN1/HPV group, as opposed to 94.3% in the CIN2/CIN3 group (P = 0.001), showing a statistically significant difference between the two groups. The quantitative method used here is simple and less subjective than the different semiquantitative methods described in the literature. In view of the different definitions of a p16 INK4 -positive case, it is almost impossible to compare the findings reported by different investigators. This study confirms the association between p16 INK4 and CIN2 and CIN3 lesions. Moreover, it shows that some low grade lesions expressed high levels of this protein. This may indicate that such low grade lesions may be predisposed to progress to high grade lesions. This means that p16 INK4 may be a strong marker for "neoplastic lesions" induced by HPV and not just an infection marker.
… -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.
Cancer detection and prevention, 2005
Human papillomavirus (HPV) infection plays a crucial role in cervical carcinogenesis. Apart from the detection of p16 protein in cervical tissues, the feasibility of the presence of HPV DNA in peripheral blood being an auxiliary marker of cervical lesions was examined. Peripheral blood samples and cervical tissues, from 36 cervical tissues from high-grade squamous intraepithelial lesions (HSIL) and 31 early invasive cervical cancers (EICC), were analyzed for HPV 16/18 DNA and HPV 16/18 E7 mRNA expression, as well as the in situ expressions of p16 and pRb to investigate the in-between associations. The prevalence of HPV 16/18 DNA in patients with EICC was relatively higher than those of HSIL, in both of cervical tissues and peripheral blood. The presence of HPV 16/18 DNA in peripheral blood was positively correlated with that in cervical tissue, as well as with p16 overexpression in cervical tissues together with a significant correlation between E7 mRNA and pRb and p16 protein expre...
Abstract Aim: Recent studies have shown that the protein level of cell cycle regulator p16 is overexpressed in high-risk HPV-related squamous cell carcinomas as well as their precursor lesions. The aim of this study was to compare the different p16 immunoexpression patterns in different cervical lesions in relation to HPV status. Materials and Methods: A total of 80 cervical tissue samples were included in this study. Seventy archival tissue biopsy samples comprised a risk group for HPV infection and/or cervical neoplasia; these were selected from the histopathology files of Al-Kadhimiya Teaching Hospital, Al-Ulwiya Teaching Hospital, Al-Yarmouk Hospital, the Medical City Department of Teaching Laboratories, and four private laboratories. The remaining 10 normal postmortem tissue biopsies were obtained from the Institute of Forensic Medicine and considered as a control group. Immunohistochemistry was done for detection p16. Results: A significant correlation was found between p16 expression and the progression of the disease (p < 0.01). A significant difference (P < 0.01) was found in the mean of p16 immunostaining between HPV-positive and negative groups in CIN II/III and ISCC. Conclusion: This study demonstrated that p16 immunohistochemical evaluation could be useful as a biomarker for the progressive malignancy in cervical lesions.
A Descriptive study of Expression of p16ink4a in Different Types of Lesions in Uterine Cervix
Abstract—Human papilloma virus (HPV) is the main reason for cervical carcinoma. The viral E7 oncogene induces increasing expression of the cyclin dependent kinase inhibitor p16 INK4a in dysplastic cells. This can be used to identify dysplastic cells in histological slides. The aim of this study was to determine the presence of p16INK4a expression and to evaluate the diagnostic value of p16 immunohistochemical (IHC) investigation in different types of lesions in the uterine cervix. The study was performed on 112 samples of cervical biopsy. All samples were selected from the records of Pathology services in University Hospital-Pleven, Bulgaria. The samples were collected in four separate groups: reactive non dysplastic changes (n=26); different degrees of intraepithelial dysplasia (n=38); invasive squamous cell carcinoma (n=32); endocervical lesions with glandular origin – microglandular hyperplasia, Adenocarcinoma in situ and invasive endocervical adenocarcinoma (n=16). In all samples immunohistochemical analysis using antibodies to p16INK4a was performed. Results. In the cases with dysplastic lesions and invasive carcinomas was found strong correlation between the level of expression of p16INK4a and the level of cervical neoplasia (p<0.01). All 26 cases (100%) of non-dysplastic cervical lesions are negative for p16INK4a. The most cases of CIN III group (14cases-87.5%) showed strong cytoplasmic and nuclear expression of p16INK4a in the whole depth of the epithelium. Strong mainly nuclear overexpression was found in all invasive cervical adenocarcinomas. Conclusions. P16INK4a overexpression is associated to high-grade precancerous lesions and cervical carcinomas. Immunohistochemical evaluation can be useful biomarker in identifying HR-HPV- infected low-grade lesions.
Journal of clinical and diagnostic research : JCDR, 2017
Cervical cancer still ranks as the most frequent cancer among women in India. Infection with Human Papilloma Virus (HPV) results in precancerous lesions and invasive cervical cancer. Interaction of HPV oncogenic proteins with cellular regulatory proteins leads to upregulation of p16INK4A, a cyclin dependent kinase inhibitor. Therefore, p16INK4A overexpression is a surrogate biomarker of HPV infection making it useful in evaluating HPV associated premalignant and malignant lesions of gynaecological tract. This study was conducted to evaluate the usefulness of p16INK4A as a biomarker in dysplastic and malignant alteration of cervical epithelium. A total of 57 specimens diagnosed histopathologically as cervical dysplasia or malignancy were included in this prospective study of two year duration. Immunohistochemical (IHC) study of p16INK4A expression was performed on normal cervical tissue samples, Cervical Intraepithelial Neoplasia (CIN) 1, CIN 2, CIN 3, squamous cell carcinoma, adenoc...