HPV16 E7 Oncoprotein As a Predictor of Diagnosis and Prognosis  in Patients with Cervical Lesions

2020 ◽  
Author(s):  
Guangnan Shuai ◽  
Junhui Xu ◽  
Meihua Liu ◽  
Xueping Zhu ◽  
Na Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Critical Value ◽  
Cervical Lesion ◽  
Pathological Examination ◽  
Low Grade ◽  
Squamous Intraepithelial Lesions ◽  
Cervical Lesions ◽  
E7 Oncoprotein ◽  
The Third ◽  
Intraepithelial Lesions

Abstract Backgroud：The early diagnosis and treatment of HSIL is a key measure to prevent the occurrence of cervical cancer. Although the methods of cervical cancer screening are becoming more and more abundant, some patients still have unnecessary colposcopy referrals. This study aim to explore the value of human papillomavirus 16 (HPV16) E7 oncoproteinin cervical lesion screening and risk assessment of the prognosis for more effective colposcopy. Method: HPV16 E7 oncoprotein in cervical exfoliated cells was detected by using E7 Oncoprotein (HPV16) Diagnostic Kit (Magnetic Partical Chemiluminescence Method). In the first part, HPV16 E7 oncoprotein in different degrees of cervical lesions was retrospectively compared to find the best critical value; In the second part, the value of this test was verified ; In the third part, the women diagnosed as low-grade squamous intraepithelial lesions (LSIL) or normal were followed up for 3 years and the outcomes were compared. Results: In the first part, the expression of HPV16 E7 oncoprotein was positively correlated with the degree of cervical lesion; The critical value determined by ROC curve is 8.68ng/ml, which is accurate in the diagnosis of high-grade squamous intraepithelial lesions (HSIL) and invasive carcinoma of cervix (CA); In the second part, there were higher sensitivity(87.1) and specificity(70) for E7 oncoprotein; HPV16 E7 oncoprotein has higher consistency with pathological examination in detection of HSIL or cervical cancer（0.573 vs 0.369) than TCT; In the third part，HPV16 E7 oncoprotein has a high positive predictive value (82.4%) and positive likelihood ratio (4.43) for the prognosis of patients with LSIL and below. Conclusions: The status of HPV16E7 oncoprotein shows important clinical value for the detection and prediction of cervical lesions. Patients with positive HPV16 E7 oncoprotein are more likely to develop the disease and have a higher risk of disease progression.

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 High prevalence of Human Papillomavirus (HPV) type 66 in low-grade cervical lesions of Mexican women

2020 ◽  
Author(s):  
Karina Juárez-González ◽  
Vladimir Paredes-Cervantes ◽  
Silvia Gordillo-Rodríguez ◽  
Saúl González-Guzmán ◽  
Xochilt Moncayo-Valencia ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cervical Cancer ◽  
Transmitted Disease ◽  
Low Grade ◽  
Mexican Women ◽  
Cervical Lesions ◽  
Hpv 16 ◽  
High Prevalence ◽  
Hpv Types ◽  
Intraepithelial Lesions

AbstractBackgroundHPV-16 infections constitute the highest risk for developing uterine cervix cancer. However, the role of other high-risk types is still controversial.ObjectiveTo analyze HR-HPV prevalence and its possible associations between HPV and risk factors related to cervical lesions among Mexican women.MethodsCross sectional study using 362 cervical samples collected between 2016 and 2017. Fourteen HR-HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) were detected by highly sensitive PCR amplification followed by reverse hybridization. Bivariate and multivariate analyses were performed to investigate the association between HPV types and risk factors among lesions.ResultsMost samples were HR-HPV positive (83.43%). HPV-16 was the most prevalent infection among negative for intraepithelial lesions or malignancy (78.6%), high-grade squamous intraepithelial lesions (50%), and cervical cancer (58.2%). HPV-66 showed an unexpected high prevalence in atypical squamous cells of undetermined significance (50%), low-grade squamous intraepithelial (45.7%), and only found in 3.6% of cervical cancers. HPV-16 was significantly prevalent among women between 30-39 years, whereas types 66 and 52 were significantly associated when previously sexually transmitted disease had occurred (p< 0.05).ConclusionsHPV-66 either in single or co-infection with other HR-HPV types (excluding 16 and 18) might be indicative of non-progressive cancer lesions. HPV-66 prevalence was unusually high in low-grade cervical lesions, predominantly in co-infection with HPV-51, and very low among cervical cancer. This should be addressed to interpret results obtained by methods that group type 66 with other HR-types.

scholarly journals Regulation of cell cycles is of key importance in human papillomavirus (HPV)-associated cervical carcinogenesis

2003 ◽  
Vol 121 (3) ◽  
pp. 128-132 ◽  
Author(s):  
Sylvia Michelina Fernandes Brenna ◽  
Kari Juhani Syrjänen
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Cell Cycle Checkpoints ◽  
Low Grade ◽  
Clinical Progression ◽  
Squamous Intraepithelial Lesions ◽  
High Risk Hpv ◽  
Intraepithelial Lesions

The rapid progress in molecular biology has allowed the identification of the genes involved in different functions of normal cells and has also improved our understanding of the mechanisms of human carcinogenesis. The human papillomavirus (HPV) is a small double-stranded DNA tumor virus and its genes can manipulate cell cycle control to promote viral persistence and replication. The E6 and E7 proteins of high-risk HPV bind to cell cycle regulatory proteins and interfere with both G1/S and G2/M cell cycle checkpoints much more effectively than the low-risk HPV. The difference between the ability of low and high-risk HPV types to induce immortalization and transformation may well lie in their abilities to interact with the various cell cycle components, resulting in the loss of multiple cell cycle checkpoints, which are important in host genome fidelity, thus potentially resulting in accumulation of genetic abnormalities. Cervical cancer is one of the leading malignancies in women worldwide, with substantial morbidity and mortality. According to current concepts, HPV is recognized as the single most important causal agent in the pathogenesis of this cancer. HPV infection clearly precedes the development of malignancy, while being regularly associated with cervical cancer precursor lesions (all grades of squamous intraepithelial lesions). HPV-infected low-grade squamous intraepithelial lesion (SIL) has three possible outcomes: a) it may regress; b) it can persist; or c) it can make a clinical progression to in situ or invasive carcinoma. It has been well established by prospective cohort studies that the spontaneous regression rate increases in parallel with follow-up duration. In contrast, the clinical progression of lesions usually takes place quite rapidly, i.e. during the first two years from diagnosis. The mechanisms responsible for this divergent clinical behavior of HPV-associated squamous intraepithelial lesions are largely unknown, but currently under intense study in different laboratories worldwide.

scholarly journals Role of Colposcopy in Detection of Dysplastic Cervical Lesion as a Screening Tool

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 33s-33s
Author(s):  
P. Gyawali ◽  
S.R. KC ◽  
S. Ghimire
Keyword(s):  
Cervical Cancer ◽  
Cervical Carcinoma ◽  
Screening Tool ◽  
Cervical Lesion ◽  
Histopathological Diagnosis ◽  
Low Grade ◽  
High Grade ◽  
Age Group ◽  
Cervical Lesions ◽  
Papanicolaou Test

Background: Age standardized cervical cancer incidence rate in Nepal is 19.2/100,000 woman, compared with 14.0 worldwide. Similarly, mortality rate is 12.0 women which is significant in comparison with 6.8 worldwide. Cervical intraepithelial neoplasm is a precursor lesion, having high transformation rate into the cervical carcinoma. Data clearly indicates that CIN 2 and 3 has more progression into cervical carcinoma. Despite the fact that Papanicolaou test has remained an important tool in the screening for cervical cancer and has contributed in significant decrease in cervical cancer, sensitivity and specificity of conventional Papanicolaou test is quite low. Colposcopy is visual inspection of cervix under magnification. Study revealed that the positive predictive rate of the colposcopic impression is better as the cervical lesion is more severe. Aim: To find out the significance of colposcopy in the detection of dysplastic cervical lesions and possible use of this method as a screening tool. Methods: This is an observational study done at Cancer Care Foundation, Nepal done from a period of January 2015 to February 2018. Permission was obtained from ethical committee and written consent was obtained from the patients. All the patients suspected having dysplastic or invasive lesions or in whom colposcopy-guided biopsy was performed; were included in the study. Relevant data were collected which included age, colposcopic diagnosis, histopathological diagnosis. Data were entered into Microsoft Excel and statistical analysis was done from statistical package SPSS 21. Results: 6109 females were screened through colposcopy. Out of these 900 patients underwent colposcopy-guided biopsy for being suspected of dysplastic lesions or inflammatory lesions. Mean age of females was 40.65 years. With colposcopy, 407 (45.2%) were suspected to have low grade lesion, followed by 401 (44.6%) high grade lesion and 15 (1.7%) carcinoma. Nonneoplastic lesions were suspected in 77 (8.6%) females. In the histopathological examination low grade dysplasia was observed in 403 (44.8%) followed by 250 (27.8%) high grade dysplasia and 8 (0.9%) carcinoma in-situ or invasive carcinoma. Similarly, 239 (26.6%) patients had nonneoplastic lesions. In colposcopy, high grade lesions were suspected more frequently in females of 41-50 years age group than in 31-40 years age group ( P < 0.01). Correlation between increasing age and dysplastic lesions were also observed ( P < 0.05). There was significant correlation between colposcopic diagnosis and histopathological diagnosis with a P value < 0.01. The sensitivity of colposcopy to diagnose dysplastic lesions were high 96.44% with positive predictive value of 62.65%. The specificity of colposcopy to diagnose various grades of dysplastic lesions is 34.98%. Conclusion: Colposcopy is highly sensitive method of screening dysplastic cervical lesions and should be used more frequently as a screening purpose.

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 HPV Testing and Pap Test: Role for a Combined Approach in a Non-Screened Population

2006 ◽  
Vol 21 (3) ◽  
pp. 149-156 ◽  
Author(s):  
I. Marchetti ◽  
K. Zavaglia ◽  
G. Bertacca ◽  
P. Aretini ◽  
B. Matteoli ◽  
...  
Keyword(s):  
Pap Test ◽  
Hpv Infection ◽  
Low Grade ◽  
Cytological Diagnosis ◽  
Squamous Intraepithelial Lesions ◽  
Cervical Lesions ◽  
Dot Blot ◽  
Screening Programs ◽  
Hpv Test ◽  
Intraepithelial Lesions

The aim of the present study was to test the polymerase chain reaction (PCR) as a tool to identify human papillomavirus (HPV) in routine cytological samples scraped from the uterine cervix. Moreover, attention has been focused on the correlation between HPV types and early intraepithelial lesions. The study involved 586 women who had undergone conventional Pap test. Analysis of HPV infection was performed by PCR and HPV typing by dot blot. In a group of 78 cases histologically diagnosed as high-grade squamous intraepithelial lesions (HSILs), the cytological diagnosis was correct in 92.3% and the HPV test was positive in 89.8% of cases; combined positivity at Pap and/or HPV tests raised this figure to 99.0%. In a group of 67 cases histologically diagnosed as low-grade squamous intraepithelial lesions (LSILs), the cytological diagnosis was correct in 73.1% and the PCR-based HPV test was positive in 64.2%; combined positivity at Pap and/or HPV tests raised this figure to 91.0%. This study confirms the limitations of screening programs based on Pap test only. Our results suggest, in fact, that adding the HPV test to primary screening could increase the yield of preinvasive cervical lesions.

Accuracy of telomerase in cervical lesions: a systematic review

2007 ◽  
Vol 17 (6) ◽  
pp. 1205-1214 ◽  
Author(s):  
M. I. Rosa ◽  
L. R. Medeiros ◽  
M. C. Bozzetti ◽  
J. Fachel ◽  
E. Wendland ◽  
...  
Keyword(s):  
Systematic Review ◽  
Intraepithelial Neoplasia ◽  
Cervix Cancer ◽  
Early Event ◽  
Low Grade ◽  
Cervical Carcinogenesis ◽  
Benign Lesions ◽  
Squamous Intraepithelial Lesions ◽  
Cervical Lesions ◽  
Intraepithelial Lesions

The detection of telomerase activity in cervix may provide information on cervical carcinogenesis and may be a marker to monitor cervical intraepithelial neoplasia transition. A quantitative systematic review was performed to estimate the accuracy of telomerase assay in cervical lesions. Studies that evaluated the telomerase test (telomerase repeated amplification protocol) for the diagnosis of cervix lesions and compared it to paraffin-embedded sections as the diagnostic standard were included. Ten studies were analyzed, which included 1069 women. The diagnostic odds ratio (DOR) for a positive telomerase test for low-grade squamous intraepithelial lesions (Lo-SIL) vs normal or benign lesions was 3.2 (95% CI, 1.9–5.6). The DOR for a positive telomerase test for high-grade squamous intraepithelial lesions (Hi-SIL) vs Lo-SIL, normal or benign lesions was 5.8 (95% CI, 3.1–10). For cervix cancer vs Hi-SIL, the DOR for a positive telomerase test was 8.1 (95% CI, 3.2–20.3) and for cervix cancer vs Lo-SIL, normal or benign lesions, it was 40.9 (95% CI, 18.2–91). Our data support the current hypothesis that telomerase may activate an early event in cervical carcinogenesis that could be associated with the initiation and progression of cervical lesions

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