Insulin-like growth factor II mRNA binding protein 3 (IMP3) expression in cervical intraepithelial neoplasia and its relationship with HIV-infection status

Sexual Health ◽  
2015 ◽  
Vol 12 (1) ◽  
pp. 22 ◽  
Author(s):  
Alessandro Del Gobbo ◽  
Emanuela Bonoldi ◽  
Fulvia Milena Cribiù ◽  
Ilaria Franceschetti ◽  
Caterina Matinato ◽  
...  

Background Cervical cancer is preventable through screening, and HIV treatment guidelines recommend that all HIV-infected women receive cervical cancer twice during the year after HIV diagnosis and annually thereafter. Different immunohistochemical markers have been studied to highlight cervical intraepithelial lesions of low and high grade, the most widely used being p16. Recent studies have shown that insulin-like growth factor mRNA binding protein 3 (IMP3) plays a role in the development of invasive squamous cell carcinoma from cervical dysplasia, both in histology and in liquid-based cytology. Methods: We evaluated the clinical significance of the immunohistochemical expression of IMP3 and p16 in histological samples of cervical intraepithelial neoplasia from 56 samples of HIV-positive and 30 samples of HIV-negative patients. Results: A significant difference was found in IMP3 and p16 protein expression between HIV-positive and HIV-negative specimens. All cases of HIV-positive low grade squamous intraepithelial neoplasia (L-SIL) with IMP3 expression progressed in high grade (H)-SIL. However, the HIV-positive patients with IMP3-negative L-SIL remained stable or had a negative follow up. The L-SIL of HIV-negative patients with IMP3 protein expression had an uneventful follow up. IMP3-positive H-SIL recurred with low- or high-grade dysplasia during follow up after conisation in both populations. All IMP3-negative L-SIL and H-SIL had negative pap tests at follow up. Conclusions: In HIV-positive cases, IMP3 showed a higher sensitivity than p16 in identifying patients at risk of progression and recurrence.

2008 ◽  
Vol 18 (6) ◽  
pp. 1289-1293 ◽  
Author(s):  
M. Cairns ◽  
N. M. Gray ◽  
M. E. Cruickshank

The psychologic and psychosexual sequelae of cervical screening and disease are well recognized but most research has focused on women with cervical intraepithelial neoplasia (CIN) or women with early (stage IB) to advanced cervical cancer. There has been little work looking at women with microinvasive cancer as a unique clinical identity. Many of these women have a similar diagnostic, treatment, and follow-up pathway to those with high-grade CIN. This could result in unrecognized and ongoing health concerns. We report on a questionnaire-based case–control study, comparing the concerns of women with microinvasive cervical cancer with those of women with high-grade CIN. Women with microinvasive cancer and controls with CIN2/3 diagnosed between 2000 and 2006, from a geographically defined population, were recruited and invited to complete a postal questionnaire consisting of the Hospital Anxiety and Depression Scale (HADS) and the Process Outcome Specific Measure (POSM). Twenty-eight women diagnosed with microinvasive cancer were identified and 18 participated (response rate 64%). Fifty-eight controls were matched by age and year of treatment with 26 responding (45%). About 18% of women with microinvasive cancer had a HADS depression score of 8 or more, compared to 12% of those with CIN (P= not significant). The HADS anxiety score of 8 or more occurred in 35% of each group. There were no significant differences in terms of POSM results for sexual activity, fertility, and developing cervical cancer in the future between cases and controls. We did not find a difference between women with a previous diagnosis of microinvasive cancer and those with high-grade CIN, in terms of ongoing concerns during their follow-up. We did not identify any additional concerns for women with microinvasive cancer in the care provided in the colposcopy service.


Sexual Health ◽  
2012 ◽  
Vol 9 (6) ◽  
pp. 574 ◽  
Author(s):  
Richard J. Hillman ◽  
Marina T. van Leeuwen ◽  
Claire M. Vajdic ◽  
Leo McHugh ◽  
Garrett P. Prestage ◽  
...  

Background We report the prevalence and predictors for high-grade anal intraepithelial neoplasia (HGAIN) in community-based cohorts of HIV-negative and HIV-positive homosexual men in Sydney, Australia. Methods: A cross-sectional study of consecutive participants in both cohorts was performed in 2005 (204 HIV-negative and 128 HIV-positive men). Anal swabs collected by a research nurse underwent cytological analysis, using the ThinPrep procedure, and human papillomavirus (HPV) testing. Participants who had cytological abnormalities other than low-grade squamous epithelial lesions (SIL) were referred for high resolution anoscopy (HRA). Results: A total of 114 men had cytological abnormalities (24.3% of HIV-negative and 57.5% of HIV-positive men, odds ratio (OR) = 4.21, 95% confidence interval (CI) 2.57–6.90). However, only three (2.3%) HIV-positive men and no HIV-negative men had high-grade SIL on anal cytology. Seventy-seven men were referred for HRA, of whom 63 (81.8%) attended. Histologically confirmed HGAIN was detected in 21 (33.3%). The prevalence of HGAIN was higher in HIV-positive men (10.8%) than in HIV-negative men (5.0%, OR = 2.29, 95% CI 0.93–5.63, P = 0.071). HGAIN was not related to age but was strongly associated with the detection of high-risk types of anal HPV (OR = 10.1, 95% CI 1.33–76.2) rather than low-risk types (OR = 1.97, 95% CI 0.74–5.25). Conclusion: HGAIN was prevalent in homosexual men across all age groups and was more than twice as common in HIV-positive men compared with HIV-negative men. The presence of high-risk anal HPV was highly predictive of HGAIN.


Author(s):  
George Du Toit ◽  
Martin Kidd

Background: Cervical cancer and human immunodeficiency virus (HIV) infection/acquired immune deficiency syndrome (AIDS) both have a high incidence in South Africa. Cervical cancer treatment of HIV-positive women poses challenges. Treatment-related changes in quality of life (QOL) of such women are important to future treatment protocols.Aim: To examine demographic data of HIV-negative and HIV-positive women at diagnosis of cervical cancer and describe their changes in QOL as a result of treatment.Methods and materials: All newly diagnosed patients with cervical cancer at Tygerberg Hospital were approached to participate in the study. The European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) and the Cervix Cancer Module (QLQ-CX24) were used. General QOL was measured with the EORTC QLQ-C30 and cervical-specific QOL with the QLQ-CX24 questionnaire. The patients completed the questionnaire at diagnosis, on completion of treatment and at 3 months’ follow-up.Results: The study included a total of 221 women of whom 22% were HIV-positive; the latter were younger and of higher educational level than the rest. Mean monthly income and stage distribution was similar between the two groups. HIV-positive patients underwent radiation therapy more commonly than chemoradiation. HIV-positive women showed statistically significantly higher loss to follow-up during the study. HIV-positive women experienced no improvement in insomnia, appetite loss, nausea, vomiting, diarrhoea, social role or any of the sexual domains. In contrast, HIV-negative women experienced statistically significant improvement in all sexual domains other than sexual/vaginal functioning. The QOL improvement of HIV-negative women was statistically significantly greater than their HIV-positive counterparts in the majority of QOL domains. Global health improved in both groups, with HIV-negative women experiencing greater improvement. HIV-positive women experienced an initial decline of peripheral neuropathy (PN) symptoms post treatment with a return to pretreatment values at 3 months’ follow-up. The change in PN was statistically significant between the HIV-negative and HIV-positive women.Conclusion: Demographic differences exist between the HIV-negative and HIV-positive groups. The differential outcome in the QOL of HIV-positive and HIV-negative women treated for cervical cancer might be related to persistence of AIDS-related symptoms on completion of cervical cancer treatment.


2012 ◽  
Vol 17 (4) ◽  
pp. 9-11
Author(s):  
E. S Sverdlova ◽  
T. V Dianova

As participation of immune system in the protection of human papillomavirus (HPV) has been proven, the incidence of HPV infection leading to cervical intraepithelial neoplasia (CIN) among HIV-positive women is 4 times higher than in HIV-negative cases. In the presence of HIV HPV implements oncoprogram during 6-12 months. Сytokine imbalance makes a significant contribution to the progression of HIV in combination with HPV. The criteria of selection of patients with HIV for therapy cytokines in CIN 2-3 (Roncoleukin used in the author's scheme). Using Ronkoleukin in combination with HAART in HIV-positive women can delay the progression of CIN 2-3 in cervical cancer. The criteria of selection of HIV female patients for the therapy with cytokines at the 2-3 stage of CIN ( Roncoleukin was used in the author's scheme) have been detected. Application Roncoleukin in combination with HAART in HIV-positive women can delay the progression of cervical cancer at the CIN 2-3 stage.


2018 ◽  
Vol 475 (17) ◽  
pp. 2749-2767 ◽  
Author(s):  
Sebastian Mackedenski ◽  
Chuyi Wang ◽  
Wai-Ming Li ◽  
Chow H. Lee

Insulin-like growth factor 2 mRNA-binding protein-1 (IMP1) has high affinity for KRAS mRNA, and it can regulate KRAS expression in cells. We first characterized the molecular interaction between IMP1 and KRAS mRNA. Using IMP1 variants with a point mutation in the GXXG motif at each KH domain, we showed that all KH domains play a critical role in the binding of KRAS RNA. We mapped the IMP1-binding sites on KRAS mRNA and show that IMP1 has the highest affinity for nts 1–185. Although it has lower affinity, IMP1 does bind to other coding regions and the 3′-UTR of KRAS mRNA. Eight antisense oligonucleotides (AONs) were designed against KRAS RNA in the nts 1–185 region, but only two, SM6 and SM7, show potent inhibition of the IMP1–KRAS RNA interaction in vitro. To test the activity of these two AONs in SW480 human colon cancer cells, we used 2′-O-methyl-modified versions of SM6 and SM7 in an attempt to down-regulate KRAS expression. To our surprise, both SM6 and SM7 had no effect on KRAS mRNA and protein expression, but significantly inhibited IMP1 protein expression without altering IMP1 mRNA level. On the other hand, knockdown of IMP1 using siRNA lowered the expression of KRAS. Using Renilla luciferase as a reporter, we found that IMP1 translation is significantly reduced in SM7-treated cells with no change in let-7a levels. The present study shows that the regulation of KRAS expression by IMP1 is complex and may involve both the IMP1 protein and its mRNA transcript.


Oncotarget ◽  
2016 ◽  
Vol 7 (42) ◽  
pp. 68397-68411 ◽  
Author(s):  
Yanlin Su ◽  
Jie Xiong ◽  
Jinyue Hu ◽  
Xin Wei ◽  
Xuelian Zhang ◽  
...  

Author(s):  
Meenakshi B. Chauhan ◽  
Sushila Chaudhary ◽  
Sunita Singh ◽  
Manasi Juneja ◽  
Smiti Nanda

Background: Cancer cervix is a leading cause of death among women worldwide. Detection of cervical cancer in precancerous stage is 100% curable. Screening with Pap smear has reduced mortality by cervical cancer in developed countries many folds. The objective of the study is to determine prevalence of Cervical Intraepithelial Neoplasia (CIN) in HIV infected women and observe for associated lower genital infections and their correlation with CD4 counts.Methods: The present study is a cross-sectional observational study conducted at PGIMS, Rohtak, Haryana for a period of 18 months. 150 HIV patients and 150 age related control cases were taken. Pap smears were taken and analyzed for cervical abnormalities and genital infections.Results: Of the 300 Pap smear 22 (7.3%) has squamous intraepithelial abnormalities and 278 (92.7%) negative for intra epithelial abnormalities. Prevalence of cervical intraepithelial abnormities among HIV positive 12% while among HIV negative it is 2.7%. Cervical intraepithelial abnormalities were found in 40% and 3.5% of patients with CD4 count <200 and >200 respectively.Conclusions: HIV increases the risk of cervical abnormalities. Frequent screening of these patients for cervical cancer is needed.


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