scholarly journals TOP2A/MCM2, p16INK4a, and cyclin E1 expression in liquid-based cytology: a biomarkers panel for progression risk of cervical premalignant lesions

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Oscar Del Moral-Hernández ◽  
Daniel Hernández-Sotelo ◽  
Luz del Carmen Alarcón-Romero ◽  
Miguel Angel Mendoza-Catalán ◽  
Eugenia Flores-Alfaro ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Precancerous Lesions ◽  
Premalignant Lesions ◽  
Low Grade ◽  
Squamous Intraepithelial Lesions ◽  
Ki 67 ◽  
Expression Levels ◽  
Cyclin E1 ◽  
Liquid Based Cytology ◽  
Intraepithelial Lesions

Abstract Background To improve the efficiency of early diagnosis systems for cervical cancer, the use of cellular and viral markers for identifying precancerous lesions with a greater probability to progress to cancer has been proposed. Several cellular proteins and markers of oxidative DNA damage have been suggested as possible biomarkers of cervical carcinogenesis; however, they have not been evaluated together. In this study, we analyzed the expression of the cellular markers p16INK4a, Ki-67, CyclinE1, TOP2A/MCM2, and telomerase, as well as the DNA oxidative damage markers ROS and 8-OHdG. The analyses were performed in liquid-based cervical cytology samples or biopsies with premalignant lesions or cervical cancer diagnosis, with the purpose of selecting a panel of biomarkers that allow the identification of precursor lesions with greater risk of progression to cervical cancer. Methods We analyzed 1485 liquid-based cytology samples, including 239 non-squamous intraepithelial lesions (NSIL), 901 low-grade squamous intraepithelial lesions (LSIL), 54 high-grade squamous intraepithelial lesions (HSIL), and 291 cervical cancers (CC). The biomarkers were analyzed by immunocytochemistry and Human Papilloma Virus (HPV) genotyping with the INNO-LiPA genotyping Extra kit. Results We found that all tested cellular biomarkers were overexpressed in samples with high risk-HPV infection, and the expression levels increased with the severity of the lesion. TOP2A/MCM2 was the best biomarker for discriminating between LSIL and HSIL, followed by p16INK4a and cyclinE1. Statistical analysis showed that TOP2A/MCM2 provided the largest explanation of HSIL and CC cases (93.8%), followed by p16INK4a (91%), cyclin E1 (91%), Ki-67 (89.3%), and telomerase (88.9%). Conclusions We propose that the detection of TOP2A/MCM2, p16INK4a and cyclin E1 expression levels is useful as a panel of biomarkers that allow identification of cervical lesions with a higher risk for progression to CC with high sensitivity and precision; this can be done inexpensively, in a single and non-invasive liquid-based cytology sample.

scholarly journals Epidemiological Approach and Precocious Diagnosis of Precancerous Cervical Lesion in Sidi Bel Abbes Region (North-West of Algeria)

2020 ◽  
Vol 10 (1-s) ◽  
pp. 72-78
Author(s):  
Samira Meziani ◽  
Khadidja Haoud ◽  
Hayet Mehida ◽  
Norddine Menadi ◽  
Fatima Zohra Chenni ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Pap Smear ◽  
Precancerous Lesions ◽  
Precancerous Lesion ◽  
Public Health Problem ◽  
Low Grade ◽  
High Grade ◽  
Squamous Intraepithelial Lesions ◽  
Pathology Laboratory ◽  
Intraepithelial Lesions

Object: Cervical cancer of the uterine (CCU) is the first cancer of the genital tract. In Algeria, this cancer remains a real public health problem. The diagnosis is still done often with advanced stages which makes the therapeutic results modest and the cost of the high care. Methodology: Our study aims to elucidate the reality of this type of pathology in the region of Sidi Bel Abbes, northwestern Algeria. This retrospective and descriptive study was devoted to the epidemiological and clinical analysis of cervical cancer cases over a period of 3 years. Results: This study shows that out of a total of 500 smears recorded between (2014-2016) at the Ana-pathology laboratory level in Sidi Bel Abbes, we found that 230 smears presented precancerous lesions according to a cytological study, atypical squamous cells of undetermined significance (ASC-US: were 18%; low-grade squamous intraepithelial lesions (LSIL) were 20%, while high-grade squamous intraepithelial lesions (HSIL) were 8%. The results obtained according to the distribution of the patients in relation to the various factors: the most affected age group is late 46-55 years with a total of 40%; precocious age of 1st report 18-20 years is (38.2%); gestation 4-5 pregnancies and parities 4-5 children with a rate of (38.70% and 32.6%) respectively ; the hormonal state in genital activity is estimated at 62.2%; patients on oral contraception (OC) have a rate of 48.9%. Finally, more than half of the patients (57.8%), were able to have a biopsy within three to four months of the last smear. In histology, the presence of a HPV (Human Papilloma Virus) low grade lesion does not predict the evolution of this lesion. Conclusion: HPV can be oncogenic or non-oncogenic. it is the oncogenic HPV infection that is the main risk factor for developing a high grade lesion  and cervical cancers outside the associated cofactors. Keywords: Pap Smear, Precancerous lesion, Cancer, Cervix, Screening

scholarly journals Characteristics of human papillomavirus infection among women with cervical cytological abnormalities in the Zhoupu District, Shanghai City, China, 2014–2019

2021 ◽  
Author(s):  
Ping Li ◽  
Qing Liu ◽  
Wei Li ◽  
Zhou Liu ◽  
Baoling Xing ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Precancerous Lesions ◽  
Hpv Infection ◽  
Single Type ◽  
Low Grade ◽  
Squamous Intraepithelial Lesions ◽  
Epidemiological Characteristics ◽  
Intraepithelial Lesions

Abstract Background: Human papillomavirus (HPV) infection is currently the main cause of cervical cancer and precancerous lesions in female patients. By analyzing 6-year patient data from Shanghai Zhoupu Hospital in China, we retrospectively analyzed the epidemiological characteristics of women to determine the relationship between HPV genotype and cytological test results.Methods: From 2014 to 2019, 23,724 cases of cervical shedding were collected from Zhoupu Hospital in Shanghai, China. By comparing the results of HPV and ThinPrep cytology test (TCT), the HPV infection rate of patients was retrospectively analyzed. HPV genotyping using commercial kits can detect 21 HPV subtypes (15 high-risk and 6 low-risk). According to the definition of the Bethesda system, seven types of cervical cytology results were involved.Results: 3,816 among 23,724 women, nearly 16.08%, were infected with HPV. The top three highest HPV prevalence rates were high-risk type infection, including HPV52 (3.19%), 58 (2.47%) and 16 (2.34%). The number of single-type HPV infections (3,480 (91.20%)) was much larger than the number of multi-type ones (336 (8.8%)). Single-type infections were mainly in women aged 50-60 (16.63%) and women under 30 (15.37%), while multi-type infections were more common in women over 60 (2.67%). By analyzing the long-term trends, between 2014 and 2019, HPV52, 58, and 16 subtypes changed significantly, and the HPV positive rate also changed significantly during this period.Among 4,502 TCT positive women, 15 (4.04%), 125 (2.64%) ,159 (1.54%), 4,202(17.71%) and 1(0.004%) had atypical glandular cells (AGC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), atypical squamous cells (ASC)and cervical adenocarcinoma, respectively. The HPV infection rates were 66.08%, 63.99%, 115.20%, 119.50%, and 31.72% for NILM, AGCs, HSILs LSILs and ASCs, respectively.Conclusions: HPV and TCT screening were very important steps in the secondary prevention of cervical cancer. Through the tracking and analysis of HPV and TCT results in this study, it can provide valuable information for Shanghai's HPV screening and prevention strategies, and provide references for clinical decision-making in the treatment of cervical cancer and precancerous lesions.

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 Characteristics of human papillomavirus infection among women with cervical cytological abnormalities in the Zhoupu District, Shanghai City, China, 2014–2019

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Ping Li ◽  
Qing Liu ◽  
Wei Li ◽  
Zhou Liu ◽  
Baoling Xing ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Precancerous Lesions ◽  
Hpv Infection ◽  
Single Type ◽  
Low Grade ◽  
Squamous Intraepithelial Lesions ◽  
Epidemiological Characteristics ◽  
Intraepithelial Lesions

Abstract Background Human papillomavirus (HPV) infection is currently the main cause of cervical cancer and precancerous lesions in female patients. By analyzing 6-year patient data from Shanghai Zhoupu Hospital in China, we retrospectively analyzed the epidemiological characteristics of women to determine the relationship between HPV genotype and cytological test results. Methods From 2014 to 2019, 23,724 cases of cervical shedding were collected from Zhoupu Hospital in Shanghai, China. By comparing the results of HPV and ThinPrep cytology test (TCT), the HPV infection rate of patients was retrospectively analyzed. HPV genotyping using commercial kits can detect 21 HPV subtypes (15 high-risk and 6 low-risk). According to the definition of the Bethesda system, seven types of cervical cytology results were involved. Results 3816 among 23,724 women, nearly 16.08%, were infected with HPV. The top three highest HPV prevalence rates were high-risk type infection, including HPV52 (3.19%), 58 (2.47%) and 16 (2.34%). The number of single-type HPV infections (3480 (91.20%)) was much larger than the number of multi-type ones (336 (8.8%)). Single-type infections were mainly in women aged 50–60 (16.63%) and women under 30 (15.37%), while multi-type infections were more common in women over 60 (2.67%). By analyzing the long-term trends, between 2014 and 2019, HPV52, 58, and 16 subtypes changed significantly, and the HPV positive rate also changed significantly during this period. Among 4502 TCT positive women, 15 (4.04%), 125 (2.64%),159 (1.54%), 4202 (17.71%) and 1 (0.004%) had atypical glandular cells (AGC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), atypical squamous cells (ASC)and cervical adenocarcinoma, respectively. The HPV infection rates were 66.08%, 63.99%, 115.20%, 119.50%, and 31.72% for NILM, AGCs, HSILs LSILs and ASCs, respectively. Conclusions HPV and TCT screening were very important steps in the secondary prevention of cervical cancer. Through the tracking and analysis of HPV and TCT results in this study, it can provide valuable information for Shanghai's HPV screening and prevention strategies, and provide references for clinical decision-making in the treatment of cervical cancer and precancerous lesions.

scholarly journals Characteristics of human papillomavirus infection among women with cervical cytological abnormalities in the Zhoupu District, Shanghai City, China, 2014–2019

2020 ◽  
Author(s):  
Ping Li ◽  
Qing Liu ◽  
Wei Li ◽  
Zhou Liu ◽  
Baoling Xing ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Precancerous Lesions ◽  
Hpv Infection ◽  
Single Type ◽  
Low Grade ◽  
Squamous Intraepithelial Lesions ◽  
Epidemiological Characteristics ◽  
Intraepithelial Lesions

Abstract Background: Human papillomavirus (HPV) infection is currently the main cause of cervical cancer and precancerous lesions in female patients. By analyzing 6-year patient data from Shanghai Zhoupu Hospital in China, we retrospectively analyzed the epidemiological characteristics of women to determine the relationship between HPV genotype and cytological test results.Methods: From 2014 to 2019, 23,724 cases of cervical shedding were collected from Zhoupu Hospital in Shanghai, China. By comparing the results of HPV and ThinPrep cytology test (TCT), the HPV infection rate of patients was retrospectively analyzed. HPV genotyping using commercial kits can detect 21 HPV subtypes (15 high-risk and 6 low-risk). According to the definition of the Bethesda system, seven types of cervical cytology results are involved.Results: 3,816 among 23,724 women, nearly 16.08%, were infected with HPV. The top three highest HPV prevalence rates were high-risk type infection, including HPV52 (3.19%), 58 (2.47%) and 16 (2.34%). The number of single-type HPV infections (3,480 (91.20%)) was much larger than the number of multi-type ones (336 (8.8%)). Single-type infections were mainly in women aged 50-60 (16.63%) and women under 30 (15.37%), while multi-type infections were more common in women over 60 (2.67%). By analyzing the long-term trends, between 2014 and 2019, HPV52, 58, and 16 subtypes changed significantly, and the HPV positive rate also changed significantly during this period.Among 4,502 TCT positive women, 15 (4.04%), 125 (2.64%) ,159 (1.54%), 4,202(17.71%) and 1(0.004%) had atypical squamous cells (ASC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), atypical glandular cells (AGC) and cervical adenocarcinoma, respectively. The HPV infection rates were 66.08%, 63.99%, 115.20%, 119.50%, and 31.72% for NILM, AGCs, HSILs LSILs and ASCs, respectively.Conclusions: HPV and TCT screening were very important steps in the secondary prevention of cervical cancer. Through the tracking and analysis of HPV and TCT results in this study, it can provide valuable information for Shanghai's HPV screening and prevention strategies, and provide references for clinical decision-making in the treatment of cervical cancer and precancerous lesions.

scholarly journals The Role of Cytology in the 21st Century: The Integration of Cells and Molecules

2016 ◽  
Vol 60 (6) ◽  
pp. 540-542 ◽  
Author(s):  
Christine Bergeron ◽  
Magnus von Knebel Doeberitz
Keyword(s):  
Cervical Cancer ◽  
Invasive Cervical Cancer ◽  
Routine Practice ◽  
Specific Marker ◽  
Low Grade ◽  
Hpv Testing ◽  
Care Providers ◽  
Squamous Intraepithelial Lesions ◽  
Ki 67 ◽  
Intraepithelial Lesions

Objectives: Cervical cancer screening test performance has been hampered by either a lack of sensitivity in Pap cytology or a lack of specificity of human papillomavirus (HPV) testing. This is disturbing for patients and a cause of high costs for health care providers. Study Design: The identification of p16INK4a as a specific marker for the neoplastic transformation of cervical squamous epithelial cells by HPVs allows the identification of HPV-transformed cells in cytopathology specimens. Results: When compared to molecular HPV tests for triaging minor cytologic atypia, such as atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions, the immunochemical detection of dual p16INK4a/Ki-67-stained cells demonstrates a significantly improved specificity with good relative sensitivity. Conclusions: HPV testing has shown earlier detection of persistent high-grade squamous intraepithelial lesions (HSIL) compared to cytology and is more effective in preventing invasive cervical cancer. The next challenge for the HPV primary screening program is to find the best method(s) for selecting, among HPV-positive women, those patients in need of immediate colposcopy because they are at a higher risk of developing a precancerous lesion. An HSIL cytology result and/or dual p16/Ki-67 staining could be the best candidates, but further randomized studies are required before these approaches can be used in routine practice.

scholarly journals Characteristics of Human Papillomavirus Infection Among Women With Cervical Cytological Abnormalities in the Zhoupu District, Shanghai City, China, 2014–2019

2020 ◽  
Author(s):  
Ping Li ◽  
Qing Liu ◽  
Wei Li ◽  
Zhou Liu ◽  
Baoling Xing ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Precancerous Lesions ◽  
Hpv Infection ◽  
Single Type ◽  
Squamous Intraepithelial Lesions ◽  
Shanghai City ◽  
Intraepithelial Lesions ◽  
Type Infection ◽  
Multiple Type

Abstract Background: Human papillomavirus (HPV) infection is the main cause of precancerous lesions and cervical cancer in women. To determine the epidemiological characteristics as well as the relationship between the HPV genotype and cytology test results among women, we retrospectively collected and analyzed the data from Zhoupu District hospital in Shanghai, China.Methods: We made a retrospective analysis of human papillomavirus prevalence rate of 23,724 women between 2014 and 2019 in the District Zhoupu of Shanghai City in China. Their cervical exfoliations were collected. HPV genotype testing was performed using a commercial kit designed to detect 21 HPV subtypes including 15 high-risk HPV subtypes(16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 ,68) and 6 low-risk HPV subtypes(6, 11, 42, 43, 44 and 81). And the thinPrep cytological test (TCT) was also performed at the same time.Results: Among all 23,724 cases, 3,816 (16.08%) women were infected with HPV. HPV52 (3.19%), HPV58 (2.47%) and HPV16 (2.34%) had higher prevalence. 3,480(91.20%) single-type infections were more common than 336(8.8%) multiple-type infections. Single-type infection was more frequently seen in women aged 50–60 years (16.63%) and <30 years (15.37%), and multiple-type infection was more common in those aged >= 60 (2.67%). Significant differences in secular trends from 2014 to 2019 were observed for subtypes HPV52, 58 and 16.HPV positive rates of women changed significantly along with the time period from 2014 to 2019.Among 4,502 TCT positive women, 15 (4.04%), 125 (2.64%) ,159 (1.54%), 4,202(17.71%) and 1(0.004%) had atypical squamous cells (ASC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), atypical glandular cells (AGC) and cervical adenocarcinoma respectively. The HPV infection rates were 66.08%, 63.99%, 115.20%, 119.50%, and 31.72% for NILM, AGCs, HSILs LSILs and ASCs, respectively.Conclusions: HPV and TCT screening were a key step in the secondary prevention of cervical cancer. Further tracking the results of HPV and TCT was an important clinical strategy for the treatment of cervical precancerous lesions. The widespread use of preventive HPV vaccines can significantly reduce the incidence of pre-neoplastic and neoplastic cervical lesions.

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.

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