scholarly journals Preliminary Study on the Expression of Testin, p16 and Ki-67 in the Cervical Intraepithelial Neoplasia

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1010
Author(s):  
Aneta Popiel ◽  
Aleksandra Piotrowska ◽  
Patrycja Sputa-Grzegrzolka ◽  
Beata Smolarz ◽  
Hanna Romanowicz ◽  
...  

Cervical cancer is one of the most common malignant cancers in women worldwide. The 5-year survival rate is 65%; nevertheless, it depends on race, age, and clinical stage. In the oncogenesis of cervical cancer, persistent HPV infection plays a pivotal role. It disrupts the expression of key proteins as Ki-67, p16, involved in regulating the cell cycle. This study aimed to identify the potential role of testin in the diagnosis of cervical precancerous lesions (CIN). The study was performed on selected archival paraffin-embedded specimens of CIN1 (31), CIN2 (75), and CIN3 (123). Moderate positive correlation was observed between testin and Ki-67 as well as testin and p16 expression in all dysplastic lesions (r = 0.4209, r = 0.5681; p < 0.0001 for both). Statistical analysis showed stronger expression of the testin in dysplastic lesions vs. control group (p < 0.0001); moreover, expression was significantly higher in HSIL than LSIL group (p < 0.0024). In addition, a significantly stronger expression of testin was observed in CIN3 vs. CIN1 and CIN3 vs. CIN2. In our study, expression of Ki-67, p16, and testin increased gradually as the lesion progressed from LSIL to HSIL. The three markers complemented each other effectively, which may improve test sensitivity and specificity when used jointly.

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Zhifang Chen ◽  
Yuejie Zhu ◽  
Rong Du ◽  
Nannan Pang ◽  
Fengbo Zhang ◽  
...  

This study is to investigate the role of regulatory B (Breg) cells in cervical cancer. In total, 70 cases of cervical cancer, 52 cases of cervical intraepithelial neoplasia (CIN), and 40 normal controls were enrolled. The percentage of Breg cells was detected by flow cytometry. Serum levels of IL-10 were measured by ELISA. The correlation between Breg cells and the clinical characterizations of cervical cancer was analyzed. The inhibition effect of Breg cells on CD8+ T cells was tested by blocking IL-10 in vitro. The percentage of CD19+CD5+CD1d+ Breg cells and the level of IL-10 of patients with cervical cancer or CIN were significantly higher than those in the control group (P<0.05). And the postoperative levels of Breg cells and IL-10 were significantly lower than the preoperative levels (P<0.05). Breg cells and the IL-10 level were positively correlated in cervical cancer patients (r=0.516). In addition, the Breg cell percentage was closely related to the FIGO stages, lymph node metastasis, tumor differentiation, HPV infection, and the tumor metastasis of cervical cancer (P<0.05). The Breg cell percentage was negatively correlated with CD8+ T cells of cervical cancer patients (r=‐0.669). The level of IL-10 in the culture supernatant of Bregs treated with CpG was significantly higher than that of non-Bregs (P<0.05). After coculture with Bregs, the quantity of CD8+ T cells to secrete perforin and Granzyme B was significantly decreased, and this effect was reversed after blocking IL-10 by a specific antibody. Breg cells are elevated in cervical cancer and associated with disease progression and metastasis. Moreover, they can inhibit the cytotoxicity of CD8+ T cells.


Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 229 ◽  
Author(s):  
Agnė Vitkauskaitė ◽  
Joana Celiešiūtė ◽  
Saulius Paškauskas ◽  
Erika Skrodenienė ◽  
Rūta Jolanta Nadišauskienė ◽  
...  

Background and objective: Lipocalin 2 (LCN2) has an oncogenic role in promoting tumorigenesis through enhancing tumor cell proliferation and the metastatic potential. The aim of our study was to determine whether serum LCN2 could serve as a diagnostic marker of cervical cancer (CC) and to evaluate the correlation between its serum concentration, the clinical stage of the cancer and Human Papilloma Virus HPV infections in women. Materials and methods: A total of 33 women with histologically proven cervical cancer (CC), 9 women with high- grade cervical intraepithelial neoplasia (HSIL) and 48 healthy women (NILM) were involved in the study. A concentration of LCN2 was assayed with the Magnetic LuminexR Assay multiplex kit. An HPV genotyping kit was used for the detection and differentiation of 15 high-risk (HR) HPV types in the liquid-based cytology medium (LBCM) and the tissue biopsy. Results: The majority (84.8%) of the women were infected by HPV16 in the CC group, and there was no woman with HPV16 in the control group (P < 0.01). Several types of HR HPV were found more often in the LBCM compared to in the tissue biopsy (P = 0.044). HPV16 was more frequently detected in the tissue biopsy than the LBCM (P < 0.05). The LCN2 level was higher in HPV-positive than in HPV-negative women (P = 0.029). The LCN2 concentration was significantly higher in women with stage IV than those with stage I CC (P = 0.021). Conclusions: Many HR HPV types, together with HPV16/18, can colonize the vagina and cervix, but often HPV16 alone penetrates into the tissue and causes CC. The serum LCN2 concentration was found to be associated not only with HR HPV infection, irrespective of the degree of cervical intraepithelial changes, but also with advanced clinical CC stage. LCN2 could be used to identify patients with advanced disease, who require a more aggressive treatment.


GYNECOLOGY ◽  
2021 ◽  
Vol 23 (4) ◽  
pp. 341-345
Author(s):  
Tatiana V. Klinyshkova ◽  
Irina B. Samosudova ◽  
Mariia S. Buyan

Aim. To evaluate the results of an immunocytochemical study of p16/Ki-67 double staining in the cervical epithelium of patients with cervical intraepithelial neoplasia (CIN) associated with high-risk human papillomavirus (HPVhr) in comparison with patients without cervical pathology. Materials and methods. The comparative study included the results of examination of 75 patients divided into 4 groups. Patients with CIN1 comprised the 1st main group (n=21), women with CIN2CIN3 the 2nd main group (n=26), the comparison group consisted of patients with latent HPV infection (n=15) and the control group (n=13). The average age of women with cervical HPV infection was 26.46.13 years. Methods of investigation: liquid cytology, colposcopic, histological examination; methods for determining HPVhr DNA; immunocytochemical examination for determining double staining of p16/Ki-67 markers, statistical analysis. Results. A positive p16/Ki-67 double staining test prevailed among patients with CIN (31.9%) compared to patients without cervical pathology (3.6%) (p=0.003) and correlated with the severity of colposcopic signs (rs=+0.397, p=0.0004). In the 1st main group of patients with verified CIN1 and in the comparison group of patients with latent infection, isolated cases of a positive test of double staining of p16/Ki-67 markers in the epithelium were recorded without significant differences between the groups (9.5 и 6.6%, p0.05). In the 2nd main group of patients with verified CIN2, CIN3, a positive test of double staining of p16 and Ki-67 was observed in every second case, dominating relative to the 1st group, the comparison group and the control group (p=0.003, p=0.005, р=0.001 respectively). In the control group, a negative double staining test was established in all cases. Conclusion. Every second patient with CIN2+ associated with HPVhr has a positive test of double staining of the cervical epithelium, with CIN1 it is observed in 9.5% of cases (p=0.003). Among patients with CIN1, there were no differences in the expression of p16/Ki-67 in epithelial cells compared to women without cervical pathology. The data of the immunocytochemical study of p16/Ki-67 in the cervical epithelium of HPVhr positive patients with CIN should be taken into account when choosing a differentiated management strategy.


GYNECOLOGY ◽  
2018 ◽  
Vol 20 (4) ◽  
pp. 29-34
Author(s):  
T V Klinyshkova ◽  
O N Mironova

The aim of the study - to determine the dynamics of expression of р16, Ki-67 in patients with HPV-associated cervical intraepithelial neoplasia (CIN) in the complex treatment with inosine pranobex. Materials and methods. The study included 62 patients with cervical HPV infection, the main group consisted of 47 patients with confirmed CIN 1 and CIN 2-3 associated to HPV high-risk, the comparison group - patients with latent HPV infection and 13 women of the control group. At the 2nd stage, a group of women with CIN 2-3 was divided into two groups: 2A (n=17) included patients who received excision treatment in combination with inosine pranobex; 2B group (n=9) patients after excision treatment (LEEP or LLETZ) without inosine pranobex. Traditional methods of examination of cervical pathology were used, including HPV genotyping, and dynamic immunocytochemical examination to determine p16, Ki-67. Results. Comparative analysis (n=75) allowed to establish the absence of differences in the expression of р16, Ki-67 and co-expression in HPV-associated CIN 1 relative to the comparison and control group. CIN 2-3 was characterized by a predominance of the levels of biomarkers in comparison with CIN 1 and latent infection (p


2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Yuejie Li ◽  
Jie Liu ◽  
Li Gong ◽  
Xingwang Sun ◽  
Wenbo Long

Abstract Background Human Papilloma Virus (HPV) DNA tests are highly sensitive and can triage women with mild lesions, improving the prognosis and diagnosis of cervical lesions. However, additional efficient strategies should be developed to improve the specificity of these tests. Methods This study aimed to evaluate the clinical value of HPV DNA load in improving the diagnosis and prognosis of cervical lesions by p16/Ki-67 testing. Histological samples were collected from 350 women with HR-HPV genotyping and analyzed by qRT-PCR. Immunohistochemical staining was used to assess p16 and Ki-67 expression and clinical performance characteristics were calculated. Results Of the cases, 271 had detectable HR-HPV infection, in which HPV-16 was most prevalent (52.0%), followed by HPV-58 (22.5%). P16/Ki-67-positivity increased with histological severity but not for HR-HPV infection. Amongst the 13 HR-HPV genotypes, only HPV-16 (P = 0.016) and HPV-58 (P = 0.004) viral loads significantly correlated with lesion severity. The P16/Ki-67/HPV DNA load co-test indicated an increased sensitivity for the detection of cervical intraepithelial neoplasia (CIN) lesions compared to p16/Ki-67 staining in HPV-16 and/or 58 positive cases. Viral load did not improve the sensitivity of p16/Ki-67 co-test in non-HPV-16 or 58 positive cases. The clinical performance of the p16/Ki-67/HPV DNA load co-test was limited for the prediction of the outcome of CIN1 lesions. However, amongst the 12 HPV-16 and/or 58 positive CIN2 cases in which return visit results were obtained, the behavior of the lesions could be predicted, with a sensitivity, specificity, positive prediction rate (PPV), and negative prediction rate (NPV) of 0.667, 1, 1 and 0.5, respectively. Conclusion Combination of the assessment of HPV DNA load with the intensity of p16 and Ki-67 staining could increase the sensitivity of CIN lesion diagnosis and predict the outcome of CIN2 in patients with a HPV-16 and/or 58 infection.


2021 ◽  
Vol 7 (1) ◽  
pp. e01-e01
Author(s):  
Pegah Hedayat ◽  
Maryam Derakhshan ◽  
Zeinab Kassab

Introduction: Cervical cancer is the second most common type of cancer among women all over the world. Objectives: This study was conducted to demonstrate the effect of intrauterine devices (IUDs) on cervical cancer and precancerous lesions development. Patients and Methods: This study was conducted in two different hospitals in Isfahan on 200 samples, since 100 of them had results indicating cervical cancer, and the rest had no abnormal lesions. For both groups, a questionnaire was filled out for IUD users and some related risk factors such as age, parity, abortions, smoking, previous Pap smear results contained sexually transmitted diseases (STDs) infections and the contraception method. Results: In this study, more cases of IUD use were recorded in the control group. We found that the use of natural methods did not prevent the development of precancerous lesions. In the results of the Pap smear, a large number were recorded as having a history of human papillomavirus (HPV). Additionally, a high percentage of cervical cancer patients’ smoking or passive smoking. We also recorded that 53% had more than two children, while the percentages of women at the birth of their first child and who did not have an abortion were almost equal in the two groups. Conclusion: Our analysis demonstrated that IUD use is a contraceptive method with the capability of lowering the risk of cervical cancer progression. There is also an association between HPV infection, smoking, age, the number of parity and the usage of natural birth control methods with the development of cancerous lesion development.


2019 ◽  
Vol 74 (1) ◽  
pp. 95-102 ◽  
Author(s):  
Nadia Escobar ◽  
Emma Plugge

Background and objectivesImprisoned women have higher rates of abnormalities at cervical screening and some studies suggest that cervical cancer is the most common cancer in this population. The aim of this work was to summarise the current evidence on the prevalence of human papilloma virus (HPV) infection, cervical cancer and precancerous lesions in women in prison worldwide and to compare these rates with the general population.MethodsWe systematically searched and reviewed published and unpublished data reporting the prevalence of any HPV infection, cervical intraepithelial neoplasia (CIN) and cervical cancer in imprisoned women. We created forest plots with prevalence estimates from studies with comparable outcomes and of prevalence ratios using data from national screening programmes as a comparison group.FindingsA total of 53 533 imprisoned women from 10 countries and 35 studies were included in the review. The prevalence of HPV among prisoners ranged from 10.5% to 55.4% with significant heterogeneity. The prevalence of CIN diagnosed by cytology in prisoners ranged from 0% to 22%. Ratios comparing the prevalence of CIN in imprisoned women to that in the community ranged from 1.13 to 5.46. Cancer prevalence estimates were at least 100 times higher than in populations participating in national screening programmes.ConclusionImprisoned women are at higher risk of cervical cancer than the general population. There is a high prevalence of HPV infection and precancerous lesions in this population. Targeted programmes for control of risk factors and the development of more effective cervical screening programmes are recommended.PROSPERO registration numberCRD42014009690.


2019 ◽  
Vol 21 (1) ◽  
pp. 222 ◽  
Author(s):  
Gislaine Curty ◽  
Pedro S. de Carvalho ◽  
Marcelo A. Soares

The microbiome is able to modulate immune responses, alter the physiology of the human organism, and increase the risk of viral infections and development of diseases such as cancer. In this review, we address changes in the cervical microbiota as potential biomarkers to identify the risk of cervical intraepithelial neoplasia (CIN) development and invasive cervical cancer in the context of human papillomavirus (HPV) infection. Current approaches for clinical diagnostics and the manipulation of microbiota with the use of probiotics and through microbiota transplantation are also discussed.


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