Association between Toll-like Receptor and Tumor Necrosis Factor Immunological Pathways in Uterine Cervical Neoplasms

2016 ◽  
Vol 103 (1) ◽  
pp. 81-86 ◽  
Author(s):  
Lucas G.G. de Matos ◽  
Eduardo B. Cândido ◽  
Paula V.T. Vidigal ◽  
Polyanna H.C. Bordoni ◽  
Rivia M. Lamaita ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Tumor Necrosis ◽  
Critical Role ◽  
Immunological Response ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Membrane Receptors ◽  
Premalignant Lesions ◽  
Cervical Lesions ◽  
Tnf Α

Introduction The immune system plays a critical role in the defense against human papillomavirus (HPV) infection and its persistence. Toll-like receptors (TLRs) are membrane receptors responsible for activation of the innate immune response, and an association between TLR expression and uterine cervical cancer has been shown. Tumor necrosis factors (TNFs) are among the main mediators of skin and mucosa inflammation. The aim of this study was to demonstrate the association between TLR and TNF immune expression and cervical cancer and premalignant cervical lesions. Methods A total of 64 embedded tissues were obtained from gynecological procedures, including 35 specimens with cervical intraepithelial neoplasia (CIN) and 10 specimens with cervical squamous cell carcinoma (CSCC) as well as 19 normal cervical samples. The expression of TLR2, TLR3, TLR4, TNF-α and TNF-β was measured by immunohistochemistry and graded into low and high levels of expression. Results There was an association between the expression levels of TLR2 and those of TNF-α and TNF-β (p = 0.01 and p = 0.021, respectively) in the cervical cancer and CIN groups. TLR4 expression was associated with TNF-α and TNF-β expression (p = 0.016 and p = 0.025, respectively) in these 2 groups. By contrast, TLR3 was not statistically associated with TNF-α or TNF-β in any of the groups. Conclusions There might be an association of the TLR2 and TLR4 pathways with the immunological response of TNF-α and TNF-β in cervical cancer. These markers are also expressed at higher levels in cervical cancer and premalignant lesions compared to normal controls.

scholarly journals Presence of histopathological premalignant lesions and infection caused by high-risk genotypes of human papillomavirus in patients with suspicious cytological and colposcopy results: A prospective study

2017 ◽  
Vol 74 (1) ◽  
pp. 24-30 ◽  
Author(s):  
Mileta Golubovic ◽  
Milena Lopicic ◽  
Natasa Terzic ◽  
Marija Djurovic ◽  
Boban Mugosa ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Prospective Study ◽  
Cervical Intraepithelial Neoplasia ◽  
Pap Test ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Premalignant Lesions ◽  
Cervical Lesions ◽  
Female Patients

Background/Aim. In patients with premalignant cervical lesions, human papillomavirus (HPV) infection, at any moment, may be spontaneously eliminated, or may persist or transform cervical epithelium from a lower to a higher degree. Due to that, it is necessary to wisely select the patients who are at high risk of cancer development. The aim of the study was to establish the interdependence between a suspicious Papanicolaou (Pap) test and colposcopy with the infection caused by high-risk genotypes of human papillomavirus and the presence of premalignant cervical lesions. Methods. This prospective study used cytological, colposcopy, real-time polymerase chain reaction (PCR) of high-risk genotypes of human papillomavirus and histopathological analysis of cervical biopsy specimen. Out of 2,578 female patients sent to cytological analyses in Clinical Center of Montenegro, during 2012, 2013 and 2014, the study included 80 women who had to submit their biopsy specimens due to a suspicious Pap test and atypical colposcopy results. Results. In the group of 80 (3.1%; n = 80/2,578) of the selected female patients with suspicious Pap test and colposcopy, 2/3 or 56 (70%) of them had cervicitis, and 1/3 or 24 (30%) had cervical intraepithelial neoplasia. The most common type in cervical intraepithelial neoplasia was HPV16 in 8 female patients, ie 61.53% out of the number of infected, or 33.33% out of the total number of premalignant lesions. Conclusion. Patients with suspicious Papanicolaou test, colposcopy results and infection which is caused by high-risk HPV infection (HPV 16 in particular) often have premalignant cervical lesions. In these cases, histopathological confirmation of lesions is mandatory, since it serves as a definitive diagnostic procedure.

A combined ultrastructural and gene molecular research for the relationship between human uterine cervical carcinoma and human papillomavirus

1990 ◽  
Vol 48 (3) ◽  
pp. 204-205
Author(s):  
Kun Lee ◽  
Jingyi Si ◽  
Ricai Han ◽  
Wei Zhang ◽  
Bingbing Tan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Dot Blot ◽  
Homologous Sequences ◽  
Normal Cervical Epithelium ◽  
The Relationship ◽  
Chronic Cervicitis

There are more supports for the view that human papillomavirus (HPV) infection might be an etiological factor in the development of cervical cancer when the association of persistent condylomata is considered. Biopsies from 318 cases with squamous cell carcinoma of uterine cervix, 48 with cervical and vulvar condylomata, 14 with cervical intraepithelial neoplasia (CIN), 34 with chronic cervicitis and 24 normal cervical epithelium were collected from 5 geographic regions of China with different cervical cancer mortalities. All specimens were prepared for Dot blot, Southern blot and in situ DNA-DNA hybridizations by using HPV-11, 16, 18 DNA labelled with 32P and 3H as probes to detect viral homologous sequences in samples. Among them, 32 cases with cervical cancer, 27 with condyloma and 10 normal cervical epitheliums were randomly chosen for comparative EM observation. The results showed that: 1), 192 out of 318 (60.4%) cases of cervical cancer were positive for HPV-16 DNA probe (Table I)

The Role of Early Colposcopy in the Management of Females with First Episode Anogenital Warts

1994 ◽  
Vol 5 (5) ◽  
pp. 343-345 ◽  
Author(s):  
K A Ward ◽  
J R Houston ◽  
B E Lowry ◽  
R D Maw ◽  
W W Dinsmore
Keyword(s):  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Cervical Cytology ◽  
First Episode ◽  
Low Grade ◽  
High Grade ◽  
Anogenital Warts ◽  
Cervical Smear ◽  
Cervical Lesions ◽  
Increased Risk

212 females attending a genitourinary medicine (GUM) clinic with first episode anogenital warts were screened by cervical cytology and colposcopy/histology for the presence of cervical epithelial abnormalities in keeping with infection by the human papillomavirus (HPV infection) and/or cervical intraepithelial neoplasia (CIN). The prevalence of cervical epithelial abnormalities detected by cervical cytology alone was 32%, rising to 56% after colposcopic examination. However, the majority of cervical lesions detected by colposcopy alone were of low grade (HPV infection and/or CIN I). Histologically confirmed high grade cervical lesions (CIN II or CIN III) were detected more frequently in those females in whom cervical cytological examination indicated dyskaryosis in keeping with any grade of CIN, compared to females without dyskaryotic changes on cervical smear ( P<0.05, chi-squared test with Yates' correction). Early colposcopy is indicated for females with anogenital warts in the presence of a cervical smear showing dyskaryosis in keeping with any grade of CIN, because of the statistically significant increased risk of detecting a potentially progressive high grade cervical lesion. In females without dyskaryotic changes on cervical smear, the value of early colposcopy is uncertain and warrants larger more long-term trials.

Human papillomavirus vaccination: evidence base for efficacy and safety

GYNECOLOGY ◽  
2021 ◽  
Vol 23 (2) ◽  
pp. 125-130
Author(s):  
Yuliya E. Dobrokhotova ◽  
Ekaterina I. Borovkova
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Hpv Vaccination ◽  
Intraepithelial Neoplasia ◽  
Evidence Base ◽  
Hpv Infection ◽  
Efficacy And Safety ◽  
Human Papillomavirus Vaccination ◽  
Hpv Types ◽  
Further Development

The article provides a literature review on the prevention of cervical cancer by human papillomavirus (HPV) vaccination. Currently, 3 vaccines are available: the 4-valent vaccine against HPV types 6, 11, 16 and 18, the 9-valent vaccine against HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58 and the bivalent vaccine against HPV types 16 and 18. Vaccination provides protection for women and men against infection with HPV and further development of HPV-associated diseases. Following immunization, seroconversion develops in 93-100% of women and in 99-100% of men and is effective in preventing incident and persistent HPV infection as well as cervical intraepithelial neoplasia. HPV immunization is ineffective in treating an existing HPV infection, genital warts, or anogenital intraepithelial neoplasia. HPV vaccination status does not affect recommendations for cervical cancer screening.

scholarly journals Role of Regulatory B Cells in the Progression of Cervical Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Zhifang Chen ◽  
Yuejie Zhu ◽  
Rong Du ◽  
Nannan Pang ◽  
Fengbo Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Intraepithelial Neoplasia ◽  
Serum Levels ◽  
Hpv Infection ◽  
Control Group ◽  
Cell Percentage

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.

scholarly journals Human papillomavirus and human telomerase RNA component gene in cervical cancer progression

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yang Liu ◽  
Pianping Fan ◽  
Yingying Yang ◽  
Changjun Xu ◽  
Yajuan Huang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Progression ◽  
Invasive Cervical Cancer ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Cancer Group ◽  
Potential Marker ◽  
Significant Difference ◽  
Human Telomerase

Abstract This study aimed to examine hTERC gene in different grades of cervical intraepithelial neoplasia (CIN) and cervical cancer, and the association between hTERC and high risk-human papillomavirus (HR-HPV) infection. Patients who underwent cervical cancer screening at the Second Affiliated Hospital of Kunming Medical University between October 2010 and December 2011 were enrolled. All patients underwent liquid-based cytology test and hybrid capture 2 (HC2) for HPV detection. hTERC was examined using fluorescence in situ hybridization (FISH). Cervical colposcopy biopsy was performed if any of the three results was positive. HC2, FISH, and pathology were compared. A total of 1200 women underwent screening, 150 patients underwent cervical biopsy: 32 in the normal group, 38 in the CIN1 group, 66 in the CIN2/3 group, and 14 in the invasive cervical cancer group. More patients had HR-HPV infection in the CIN2/3 group and ICC group compared with the CIN1 group. hTERC increased with increasing histological dysplasia. There was significant difference in hTERC positive rate between each of the three groups. More patients with hTERC gene amplification were observed in the positive HR-HPV group than in the HR-HPV negative group. In conclusion, hTERC is a potential marker for precancerous cervical cancer lesions. hTERC might be correlated with HR-HPV infection in cervical diseases.

Discovery of candidate gene expression signatures in peripheral blood for the screening of cervical cancer

2020 ◽  
Vol 14 (2) ◽  
pp. 109-118 ◽  
Author(s):  
Qiuling Ma ◽  
Yong Shao ◽  
Wei Chen ◽  
Cheng Quan ◽  
Yanhui Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Real Time ◽  
Real Time Pcr ◽  
Peripheral Blood ◽  
Area Under The Curve ◽  
Intraepithelial Neoplasia ◽  
Sequencing Analysis ◽  
Quantitative Real Time Pcr ◽  
Cervical Lesions

Aim: To investigate whether cervical cancer (CC) and cervical intraepithelial neoplasia (CIN) can be screened by analyzing gene expression profiling of peripheral blood. Methods: RNA-sequencing analysis of blood was performed on 11 CC patients, 21 CIN patients and 19 healthy controls (H). Fifty-nine genes were validated by quantitative real-time PCR using blood samples from 46 H, 83 CC and 32 CIN patients. Results: There were significant differences in the expression levels of six genes between CC and H, five genes between CIN and H and four genes between CC and CIN (p < 0.05). Four genes discriminated cervical lesions from H with a sensitivity of 82.61%, a specificity of 87.83% and an area under the curve of 0.8981. Three genes discriminated CC from CIN with a sensitivity of 53.13%, a specificity of 96.39% and an area under the curve of 0.7786. Conclusion: Our findings provided a promising noninvasive quantitative real-time PCR diagnostic assay of CC and CIN.

scholarly journals The ratio of serum Angiopoietin-1 to Angiopoietin-2 in patients with cervical cancer is a valuable diagnostic and prognostic biomarker

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3387 ◽  
Author(s):  
Ping Yang ◽  
Na Chen ◽  
Dongyun Yang ◽  
Janet Crane ◽  
Shouhua Yang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Intraepithelial Neoplasia ◽  
Roc Curves ◽  
Enzyme Linked Immunosorbent Assay ◽  
Advanced Tumor Stage ◽  
Cervical Lesions ◽  
Advanced Tumor ◽  
Angiopoietin 1

Objectives Angiopoietins have been found to play essential roles in tumor angiogenesis. The present study was aimed at investigating the diagnostic and prognostic values of serum angiopoietin 1 and 2 (sAng-1 and sAng-2) in cervical cancer. Methods The sAng-1 and sAng-2 concentrations were analyzed in 77 women with cervical cancer, 44 women with cervical intraepithelial neoplasia (CIN) and 43 women without cervical lesions by enzyme-linked immunosorbent assay. The diagnostic values of sAng-1, sAng-2 and sAng-1/sAng-2 were evaluated by receiver operating characteristic (ROC) curves. The Ang-1 and Ang-2 expression in cervical cancer tissues as well as microvessel density (MVD), were assessed by immunohistochemistry. Results The concentration of sAng-2 gradually increased and the sAng-1/Ang-2 ratio was gradually decreased from normal control to CIN, then to squamous cell cancer, and the sAng-1/sAng-2 ratio was also significantly decreased in adenocarcinoma. The area under ROC curves of sAng-2 and sAng-1/sAng-2 ratio for discriminating cervical cancer from normal were 0.744 and 0.705, respectively. Decreased sAng-1/sAng-2 was significantly associated with advanced tumor stage, poor differentiation, lymph-vascular space invasion and high MVD. sAng-2 was positively correlated with the Ang-2 expression in cervix epithelia. A high sAng-1/sAng-2 ratio was associated with a longer progression-free survival and a longer overall survival in cervical cancer patients. Conclusions These findings suggest that sAng-2 and the sAng-1/sAng-2 ratio may be valuable diagnostic and prognostic biomarkers for cervical cancer.

scholarly journals Clinical Significance of the Interaction between Human Papillomavirus (HPV) Type 16 and Other High-Risk Human Papillomaviruses in Women with Cervical Intraepithelial Neoplasia (CIN) and Invasive Cervical Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Arsenio A. Spinillo ◽  
Mattia M. Dominoni ◽  
Anna A. C. Boschi ◽  
Cecilia C. Sosso ◽  
Giacomo G. Fiandrino ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Residual Disease ◽  
Invasive Cervical Cancer ◽  
Intraepithelial Neoplasia ◽  
Human Papillomaviruses ◽  
Multiple Infections ◽  
Cervical Lesions ◽  
Hpv 16 ◽  
The Impact

The aim is to evaluate the clinical consequences of coinfection between HPV 16 and other high-risk HPVs among women with a histological diagnosis of CIN or invasive cervical cancer. A total of 2985 women, with a diagnosis of either CIN or cancer (<IB) on cervical or cone biopsy, were included. HPV genotypes were identified using the INNO-LiPA HPV genotyping assay, version EXTRA, on cervical scraping, before the colposcopic evaluation and the colposcopic biopsies or conization. In the overall population, HPV16 interacted positively with HPV18 (RR = 2, 95% CI 1.5–2.6) and negatively with HPV33, 51, 52, and 66, in log-linear analysis. There was an excess of CIN3 diagnoses among subjects coinfected with HPV16 and HPV18 or HPV52, although the absolute number of cases was relatively small. In a logistic model, the odds ratio of CIN3+ associated with coinfection of HPV16 and HPV18 (OR = 3.8, 95% CI 2.5–5.7, p = 0.004 compared to single HPV16) or HPV52 (OR = 3.6, 95% CI 2.6–5.1, p = 0.009 compared to single HPV) was higher than that associated with single HPV 16 infections. Finally, multiple infections had no effect on residual disease and did not influence the recurrence of high-grade CIN during a median follow-up of 25 months (IR 17–41). HPV16 interacted positively with HPV18 and negatively with HPV33, 51, 52, and 66 supporting the notion that HPV16 interacts mostly negatively with other HR-HPVs in CIN lesions. Among specimens coinfected with HPV16 and 18 or 52, there was an excess of CIN3+ although the impact on the prevalence of severe cervical lesions was limited.

State of HPV16 integration in Lithuanian women with cervical neoplasia

Open Medicine ◽  
2011 ◽  
Vol 6 (2) ◽  
pp. 205-212
Author(s):  
Agne Sepetiene ◽  
Zivile Gudlevicienė ◽  
Zana Bumbuliene ◽  
Grazina Drasutiene ◽  
Janina Didziapetriene
Keyword(s):  
Cervical Cancer ◽  
Hpv Infection ◽  
Rapid Progression ◽  
The European Union ◽  
Cervical Lesions ◽  
Hpv 16 ◽  
Hpv Dna ◽  
Cin Iii ◽  
Cell Genome ◽  
Virus Integration

AbstractCervical cancer morbidity and mortality in Lithuania is one of the biggest in the European Union. The main risk factor of cervical cancer is human papillomavirus (HPV). The deletion of the HPV E2 gene influences HPV DNA integration into the cell genome, as well as a rapid progression of cervical lesions. The purpose of this study is to determine HPV, its types, and HPV 16 integration in different grades of cervical intraepithelial neoplasias (CIN). 253 women with cytological lesions were involved in the study. After a histology, 31 women were diagnosed with CIN I, 35 with CIN II, and 51 with CIN III. The biggest prevalence of HPV infection was detected in women younger than 25 years old (69.7%) and in women with CIN II (90.9%). HPV 16 was detected in 67.8% of all cases, with the highest prevalence in CIN III (84.4%). A partial integration form was detected in 65.0% of HPV 16 infected women, a complete virus integration in 26.5%, and an episomal form in 8.4% of cases. Our study concludes that in all the cases confirmed using a histology, the partial virus integration form of CIN was identified the most. It was less frequently detected in CIN I cases (60.0%), but more frequently in CIN II and CIN III cases (72.8 and 69.3%, respectively).

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