P16INK4A Immunohistochemistry as a Gold Standard for Cervical Cancer and Precursor Lesions Screening

2020 ◽  
Author(s):  
Mahdieh FARZANEHPOUR ◽  
Ahad MUHAMMADNEJAD ◽  
Setareh AKHAVAN ◽  
Mir Nader EMAMI RAZAVI ◽  
Somayeh JALILVAND ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Invasive Cervical Cancer ◽  
Immunohistochemical Analysis ◽  
Human Papillomaviruses ◽  
Low Grade ◽  
Operating Characteristics ◽  
Hpv Dna ◽  
Diagnosis And Prognosis ◽  
Tissue Specimens ◽  
Intraepithelial Lesions

Background: High-risk (HR) Human papillomaviruses (HPVs) are known as the main factors implicated in the pathogenesis of cervical preinvasive and invasive lesions. Therefore, the presence or absence of HR-HPV can be followed for the prognosis of low-grade and high-grade squamous intraepithelial lesions. Since the overexpression of p16INK4a protein depends on the presence of transcriptionally-active HPV, and due to its availability and simple interpretation, it may be considered as a proper marker to diagnose cervical cancer. Methods: An immunohistochemical analysis of p16INK4a was performed in 72 cervical tissue specimens at Imam Khomeini Complex Hospital (Tehran, Iran) from 2016 to 2018. The performance parameters were calculated and compared using receiving operating characteristics curve (ROC) details. Results: p16INK4a is significantly up-regulated in the cervical cancer samples in comparison with that in normal samples. Moreover, the ROC data showed the potential ability of p16INK4a under determined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. The molecular typing disclosed the attendance of HPV DNA in 44.4% of cases (32/72) with a predominance of HPV type 16. Conclusion: The molecular biomarker p16INK4a can be a good candidate for the early diagnosis and prognosis of cervical cancer in HPV-infected patients. Considering the increase in the expression level of p16INK4a in cancer and precancer tissues, p16INK4a may be used for early detection of cervical cancer.

scholarly journals Antibodies against Early Proteins of Human Papillomaviruses as Diagnostic Markers for Invasive Cervical Cancer

1998 ◽  
Vol 36 (2) ◽  
pp. 475-480 ◽  
Author(s):  
Wolfgang Meschede ◽  
Klaus Zumbach ◽  
Joris Braspenning ◽  
Martin Scheffner ◽  
Luis Benitez-Bribiesca ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Invasive Cervical Cancer ◽  
Human Papillomaviruses ◽  
Antibody Detection ◽  
Diagnostic Tools ◽  
Immunological Monitoring ◽  
Hpv Dna ◽  
Native Proteins ◽  
Human Sera ◽  
E6 And E7

Cervical cancer is the most prevalent tumor in developing countries and the second most frequent cancer among females worldwide. Specific human papillomaviruses (HPVs) and, most notably, HPV types 16 and 18 are recognized as being causally associated with this malignancy. Antibodies against early HPV proteins E6 and E7 have been found more often in patients with tumors than in controls. Existing peptide enzyme-linked immunosorbent assays (ELISAs) for the detection of anti-E6 and anti-E7 antibodies in human sera have low levels of sensitivity and specificity and thus are not suitable for use as diagnostic tools. Based on highly purified recombinant native proteins, we developed four sandwich ELISAs for the detection of antibodies against HPV type 16 and 18 E6 and E7 proteins. We demonstrate their sensitivities and high degrees of specificity for cervical cancer. Among a total of 501 serum specimens from unselected patients with invasive cervical cancer, 52.9% reacted positively in at least one of the four assays. In contrast, among 244 serum specimens from control subjects without cervical cancer, only 2 reactive serum specimens (0.8%) were found. For 19 of 19 antibody-positive patients, the HPV type indicated by seroreactivity was identical to the HPV DNA type found in the tumor, which also indicates a high degree of specificity for antibody detection with respect to HPV type. In a direct comparison of 72 serum specimens from patients with cervical cancer, 56% of the specimens reacted in at least one of the four protein ELISAs, whereas 40% reacted in at least one of seven peptide ELISAs covering the four antigens. These assays could be of value for the detection of invasive cervical cancer in settings in which cytology-based early tumor screening is not available, for the clinical management of patients diagnosed with cervical cancer, and for the immunological monitoring of E6 and E7 vaccination trials.

scholarly journals HPV-Chlamydial Coinfection, Prevalence, and Association with Cervical Intraepithelial Lesions: A Pilot Study at Mbarara Regional Referral Hospital

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Frank Ssedyabane ◽  
Diaz Anaya Amnia ◽  
Ronald Mayanja ◽  
Aisagbonhi Omonigho ◽  
Charles Ssuuna ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cervical Cancer ◽  
Chlamydia Trachomatis ◽  
Pap Smear ◽  
Low Grade ◽  
Cervical Lesions ◽  
Cross Sectional ◽  
Hpv Dna ◽  
Cervical Intraepithelial Lesions ◽  
Intraepithelial Lesions

Background. Human Pappilloma Virus (HPV) is the necessary cause of cervical cancer. A number of risk factors are believed to influence the role of HPV in the development of cervical cancer. This is so because majority of HPV infections are cleared and only a few are able to result into cancer. Chlamydia trachomatis (CT) is considered a potential cofactor in the development of cervical intraepithelial neoplasia (CIN), although different studies have produced contradicting information (Silins et al., 2005, Bellaminutti et al., 2014, and Bhatla et al., 2013). The objective of this cross-sectional study was to determine the prevalence and association of HPV-Chlamydial coinfection with cervical intraepithelial lesions and other risk factors for cervical intraepithelial lesions at a hospital in south western Uganda (MRRH). Methods. The study included 93 participants, with an age range of 25 to 80 years, from whom cervical specimens were collected and enrolment forms were completed upon consent. Experienced midwives collected one cervical smear and two endocervical swabs from each participant. The swabs were used for HPV DNA and Chlamydia trachomatis antigen testing. Data was entered in Microsoft excel and analysed using STATA 12 software. With the help of spearman’s correlation at the 0.05 level of significance, bivariate and multivariate analysis were done by logistic regression, to determine associations of risk factors to cervical lesions. Results. The results showed the prevalence of HPV-Chlamydial coinfection to be 8.6% (8/93). Positive Pap smear results were found in 60.22% (56/93) participants, most of whom had low grade squamous intraepitherial lesion (LSIL) (54.84%). HPV-Chlamydial coinfection showed a significant correlation with a positive cytology result and only relatively significantly correlated with LSIL grade of cytological positivity. HPV was found to be the risk factors associated with cervical intraepithelial lesions at MRRH. Conclusion. HPV, Chlamydia, and HPV-Chlamydial coinfection are prevalent infections and there is a likelihood of association between HPV-Chlamydial coinfection and with cervical intraepithelial lesions. This study recommends general sexually transimitted infections (STIS) screening for every woman that turns up for cervical cancer screening and a larger study, probably a multicentre study.

scholarly journals The Epidemiology of Human Papillomavirus Infection and Cervical Cancer

2007 ◽  
Vol 23 (4) ◽  
pp. 213-227 ◽  
Author(s):  
F. Xavier Bosch ◽  
Silvia de Sanjosé
Keyword(s):  
Cervical Cancer ◽  
Invasive Cervical Cancer ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Transmitted Infection ◽  
Hpv Dna ◽  
Sexually Transmitted ◽  
Papillomavirus Infection ◽  
Simplex Virus

Cervical cancer has been recognized as a rare outcome of a common Sexually Transmitted Infection (STI). The etiologic association is restricted to a limited number of viral types of the family of the Human Papillomaviruses (HPVs). The association is causal in nature and under optimal testing systems, HPV DNA can be identified in all specimens of invasive cervical cancer. As a consequence, it has been claimed that HPV infection is a necessary cause of cervical cancer. The evidence is consistent worldwide and implies both the Squamous Cell Carcinomas (SCC), the adenocarcinomas and the vast majority (i.e. > 95%) of the immediate precursors, namely High Grade Squamous Intraepithelial Lesions (HSIL)/Cervical Intraepithelial Neoplasia 3 (CIN3)/Carcinomain situ. Co-factors that modify the risk among HPV DNA positive women include the use of oral contraceptives (OC) for five or more years, smoking, high parity (five or more full term pregnancies) and previous exposure to other sexually transmitted diseases such as Chlamydia Trachomatis (CT) and Herpes Simplex Virus type 2 (HSV-2). Women exposed to the Human Immunodeficiency Virus (HIV) are at high risk for HPV infection, HPV DNA persistency and progression of HPV lesions to cervical cancer.

scholarly journals Viral and Cellular Biomarkers in the Diagnosis of Cervical Intraepithelial Neoplasia and Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Maria Lina Tornesello ◽  
Luigi Buonaguro ◽  
Paolo Giorgi-Rossi ◽  
Franco M. Buonaguro
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Viral Infections ◽  
Invasive Cervical Cancer ◽  
High Sensitivity ◽  
Intraepithelial Neoplasia ◽  
Premalignant Lesions ◽  
Low Grade ◽  
Hpv Dna ◽  
Hpv E6

Cervical cancer arises from cells localized in the ectoendocervical squamocolumnar junction of the cervix persistently infected with one of about 13 human papillomavirus (HPV) genotypes. The majority of HPV infections induces low grade squamous epithelial lesions that in more than 90% of cases spontaneously regress and in about 10% eventually progress to high grade lesions and even less frequently evolve to invasive cancer. Tumor progression is characterized by (1) increased expression of E6 and E7 genes of high risk HPVs, known to bind to and inactivate p53 and pRb oncosuppressors, respectively; (2) integration of viral DNA into host genome, with disruption of E2 viral genes and host chromosomal loci; and (3) molecular alterations of key regulators of cell cycle. Molecular markers with high sensitivity and specificity in differentiating viral infections associated with cellular abnormalities with high risk of progression are strongly needed for cervical cancer screening and triage. This review will focus on the analysis of clinical validated or candidate biomarkers, such as HPV DNA, HPV E6/E7 mRNA, HPV proteins, p16(INK4a) and Ki67, TOP2A and MCM2 cellular factors, and DNA methylation profiles, which will likely improve the identification of premalignant lesions that have a high risk to evolve into invasive cervical cancer.

scholarly journals Immunohistochemical expression of p16ink4a in inflammatory, preneoplastic and neoplastic cervical lesions

2015 ◽  
Vol 68 (3-4) ◽  
pp. 85-92
Author(s):  
Radoslav Gajanin ◽  
Zivorad Gajanin ◽  
Zoran Vujkovic ◽  
Vesna Gajanin ◽  
Zdenka Gojkovic ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Surrogate Marker ◽  
Immunohistochemical Analysis ◽  
Human Papillomaviruses ◽  
Low Grade ◽  
Main Role ◽  
High Grade ◽  
Cervical Lesions ◽  
Inflammatory Lesions ◽  
Significant Difference

Introduction. High-risk human papilloma viruses play a main role in the development of cervical dysplasias and carcinomas. p16INK4a can be considered as a surrogate marker of active highrisk human papillomaviruses infection in dysplastic and neoplastic cells of the cervix. This study was aimed at determining the presence and level of p16INK4a expression in inflammatory, preneoplastic and neoplastic lesions of the cervix. Material and Methods. The study was performed on 109 samples of cervical biopsy. Cervical cancer was diagnosed in 36 patients, 34 patients had a preneoplastic change (dysplasia) in stratified squamous cervix epithelium and a nonspecific inflammatory process was found in 39 patients. In all samples, immunohistochemical analysis using antibodies to p16INK4a was performed. Results. The expression of p16INK4a was verified in all cases of cervical cancer (100%), in 67.65% of dysplastic cervical lesions and in 38.5% of inflammatory lesions. A statistically highly significant difference was found in the presence and level of expression among neoplasic, dysplastic and inflammatory lesions of the cervix (?? = 76.02, p < 0.001). The expression was more frequent and had a higher level in neoplastic and high grade dysplastic lesions compared to expression in inflammatory lesions and low grade dysplasias. Conclusion. The analysis of the presence of p16INK4a can differentiate non-neoplastic, high grade preneoplastic and neoplastic changes of the cervix. The use of p16INK4a in interpreting borderline lesions of the cervix can enable a rational therapeutic treatment of patients.

scholarly journals Protein Phosphorylation in Serine Residues Correlates with Progression from Precancerous Lesions to Cervical Cancer in Mexican Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Juan Ramón Padilla-Mendoza ◽  
Arturo Contis-Montes de Oca ◽  
Mario Alberto Rodríguez ◽  
Mavil López-Casamichana ◽  
Jeni Bolaños ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Protein Phosphorylation ◽  
Precancerous Lesions ◽  
Human Papillomaviruses ◽  
Serine Phosphorylation ◽  
Low Grade ◽  
Squamous Intraepithelial Lesions ◽  
Cervical Lesions ◽  
Phosphorylated Proteins ◽  
Intraepithelial Lesions

Protein phosphorylation is a posttranslational modification that is essential for normal cellular processes; however, abnormal phosphorylation is one of the prime causes for alteration of many structural, functional, and regulatory proteins in disease conditions. In cancer, changes in the states of protein phosphorylation in tyrosine residues have been more studied than phosphorylation in threonine or serine residues, which also undergo alterations with greater predominance. In general, serine phosphorylation leads to the formation of multimolecular signaling complexes that regulate diverse biological processes, but in pathological conditions such as tumorigenesis, anomalous phosphorylation may result in the deregulation of some signaling pathways. Cervical cancer (CC), the main neoplasm associated with human papillomavirus (HPV) infection, is the fourth most frequent cancer worldwide. Persistent infection of the cervix with high-risk human papillomaviruses produces precancerous lesions starting with low-grade squamous intraepithelial lesions (LSIL), progressing to high-grade squamous intraepithelial lesions (HSIL) until CC is generated. Here, we compared the proteomic profile of phosphorylated proteins in serine residues from healthy, LSIL, HSIL, and CC samples. Our data show an increase in the number of phosphorylated proteins in serine residues as the grade of injury rises. These results provide a support for future studies focused on phosphorylated proteins and their possible correlation with the progression of cervical lesions.

scholarly journals Human papillomaviruses 16 and 58 are distributed widely among women living in Shanghai, China, with high-grade, squamous intraepithelial lesions

2018 ◽  
Vol 147 ◽  
Author(s):  
J. Xu ◽  
Z. Xia ◽  
L. Wang ◽  
B. Yang ◽  
Y. Zhu ◽  
...  
Keyword(s):  
Human Papillomaviruses ◽  
Low Grade ◽  
High Grade ◽  
Squamous Intraepithelial Lesions ◽  
Hpv 16 ◽  
Hpv Dna ◽  
Control And Prevention ◽  
Intraepithelial Lesion ◽  
Hpv Dna Tests ◽  
Intraepithelial Lesions

AbstractThe distribution of human papillomaviruses (HPVs) must be understood for the control and prevention of cervical cancer. Community-based Papanicolaou and HPV DNA tests were performed on 41 578 women. The prevalences of HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 were assessed. In total, 10% women were infected/co-infected by these HPVs. The infection rate increased from 7.1% in women aged ⩽30 years to 10.4% in those aged 50–60 years, and then decreased slightly to 9.9% in those aged >60 years. The HPV 16 and 58 positivity rates were significantly higher among women with high-grade squamous intraepithelial lesions (HSILs) than among those with cervicitis/negativity for intraepithelial lesion or malignancy (NILM) or low-grade SILs (LSILs). The HPV 18, 52 and 68 infection rates were significantly lower in women with HSILs than in those with NILM or LSILs. The proportion of women infected by multiple HPV strains was higher among those with HSILs. The proportions of the five most common genotypes, HPV 16, 18, 33, 52 and 58, increased with the number of co-infecting strains. HPV 16 and 58 were the high-risk HPVs in the Shanghai community and should be the focus in HPV screening and vaccination.

scholarly journals A Comparative Study of Manual Liquid-Based Cytology with the Conventional Pap Smear for Cervical Cancer Screening in a Tertiary Care Hospital of Mandya, Karnataka

2021 ◽  
Vol 8 (16) ◽  
pp. 1009-1014
Author(s):  
Manjunath M.R ◽  
Sheetal Sheetal
Keyword(s):  
Cervical Cancer ◽  
Pap Smear ◽  
Invasive Cervical Cancer ◽  
Tertiary Care ◽  
Human Papillomaviruses ◽  
Care Hospital ◽  
Cancer Cervix ◽  
Hpv Dna ◽  
Bethesda System ◽  
Liquid Based Cytology

BACKGROUND A long pathological process for investigation of precursor lesion squamous intraepithelial lesion (SIL) leads to invasive cervical cancer. This SIL can be detected much earlier before the lesion progresses to invasive cancer. For greater than fifty years, screening for cancer cervix was done by conventional scrape smears and stained by Papanicolaou [Pap] stain but conventional Pap smears (CPAP) have been reported to have low sensitivity. To overcome these drawbacks manual liquid-based cytology [MLBC] was introduced. The objective of this study was to screen females for cervical cancer using CPAP and MLBC techniques and compare the results of these techniques. METHODS Cervical cytology samples were obtained from 120 non-pregnant females through specialised Uprep cytobrush with a detachable head. Thus, obtained samples were first smeared onto a clean glass slide for CPAP smear, and the whole head to cytobrush was dropped into the specialised Uprep liquid preservative medium and processed by using Uprep Cytospin machine to obtain MLBC smears. Both the smears were stained by conventional Pap stain and reported according to 2014 Bethesda system. RESULTS In this study, the CPAP method had a greater number of unsatisfactory smears than that of MLBC method which was statistically significant. MLBC identified more number of intraepithelial lesions when compared to CPAP and MLBC had an increased detection rate [IDR] of 73.68 % over CPAP. CONCLUSIONS Analysis of our results showed that MLBC had more advantages over CPAP. Since the cost effective MLBC has an improved rate of detection of abnormal lesions, MLBC can be used as a routine technique for screening of cancer cervix in India. Also, MLBC offers an important advantage of performing both human papillomaviruses deoxyribonucleic acid (HPV DNA) test and cytological analysis on a single sample. KEYWORDS Cervical Cancer, Conventional Pap Smear, Manual Liquid Based Cytology, Human Papilloma Virus (HPV DNA), Bethesda System

AgNOR Pleomorphic Count as a Tumor Marker in Cervical Carcinogenesis and Feasibility of Its Introduction in Cervical Cancer Screening Programs to Discriminate High-Risk Cases of Squamous Intraepithelial Lesions of the Cervix

2019 ◽  
Vol 63 (5) ◽  
pp. 371-378 ◽  
Author(s):  
Anand N. Srivastava ◽  
Jata S. Misra ◽  
Urmilla Singh ◽  
Mohsin Khan ◽  
Syed Raza
Keyword(s):  
Cervical Cancer ◽  
Cancer Screening ◽  
High Risk ◽  
Tumor Marker ◽  
Cervical Cancer Screening ◽  
Low Grade ◽  
Squamous Intraepithelial Lesions ◽  
Hpv Dna ◽  
Screening Programs ◽  
Intraepithelial Lesions

Background: AgNOR pleomorphism has been widely used for its diagnostic importance in differentiating premalignant and malignant lesions of different human neoplasms. However, an evaluation of its potential for discriminating cases of high-risk squamous intraepithelial lesions of the cervix (SIL) has been rarely attempted. Aim: The tumor marker potential of AgNOR pleomorphism counts was assessed by correlating high and low mean counts in low-grade SIL (LSIL) cases with persistence or regression of the lesion and HPV positivity. Materials and Methods: The 115 LSIL cases selected for the study were registered from the ongoing cervical cancer screening of the rural population of Lucknow West. Silver nitrate staining for AgNOR counts and HPV DNA testing were done in all 115 cases. Results: The AgNOR counts in the 115 LSIL cases revealed low counts in 92 and high counts in 23 cases. Follow-up, available in 107 cases, revealed persistence of the lesion in 21 of the 23 cases with high counts and in 4 of the 84 cases with low counts. HPV positivity showed a strong correlation with high counts. Persistence of LSIL was also more frequent with high AgNOR counts and in HPV-positive cases. Conclusions: The study showed a correlation of high mean AgNOR counts with HPV positivity and persistence of LSIL.

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