Survivin and Telomerase Expression in the Uterine Cervix of Women With Human Papillomavirus-Induced Lesions

Introduction:Infection by human papillomavirus is the most important risk factor in the pathogenesis of uterine cervical cancer. The aims of this study were to evaluate the expression of survivin protein and telomerase enzyme in samples of uterine cervix from women with human papillomavirus-induced lesions and to determine the relationship between survivin and telomerase expression and the different grades of cervical squamous intraepithelial neoplasia and invasive cervical carcinoma.Methods:Biopsy samples from the uterine cervix of 105 women aged 18 to 80 years were analyzed. The patients were divided into 5 groups: WN group, 20 patients without neoplasia; CIN-1 group, 24 patients with grade 1 cervical intraepithelial neoplasia (CIN), grade 1; CIN-2 group, 20 patients with CIN grade 2; CIN-3 group, 24 patients with CIN, grade 3; and ICC group, 17 patients with invasive cervical carcinoma. Human papillomavirus detection, telomerase activity, and survivin expression were assessed using polymerase chain reaction (PCR), real-time PCR (RT-PCR), and immunochemistry, respectively.Results:There was a significant increase in the expression of telomerase and survivin associated with the severity of the lesion.Conclusions:The results suggest that mechanisms that promote both cell proliferation (telomerase activity) and cell survival (survivin expression) are active in cervical cancer and its precursor lesions. There was a negative correlation between survivin expression and the number of PCR cycles necessary to detect telomerase activity in the total sample, achieving statistical significance in patients in the CIN-3 group.

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Genotype distribution of human papillomavirus (HPV) in histological sections of cervical intraepithelial neoplasia and invasive cervical carcinoma in Madrid, Spain

BMC Cancer ◽

10.1186/1471-2407-12-533 ◽

2012 ◽

Vol 12 (1) ◽

Cited By ~ 14

Author(s):

Benjamín García-Espinosa ◽

Ernesto Moro-Rodríguez ◽

Emilio Álvarez-Fernández

Keyword(s):

Human Papillomavirus ◽

Cervical Intraepithelial Neoplasia ◽

Cervical Carcinoma ◽

Intraepithelial Neoplasia ◽

Genotype Distribution ◽

Invasive Cervical Carcinoma ◽

Histological Sections

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An ensemble feature ranking framework for the assessment of the efficacy of cervical cancer detection tests and human papillomavirus genotypes in the detection of high-grade cervical intraepithelial neoplasia and cervical carcinoma

2015 IEEE 15th International Conference on Bioinformatics and Bioengineering (BIBE) ◽

10.1109/bibe.2015.7367657 ◽

2015 ◽

Author(s):

Panagiotis Bountris ◽

Charalampos Tsirmpas ◽

Maria Haritou ◽

Abraham Pouliakis ◽

Ioannis Kouris ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Cervical Intraepithelial Neoplasia ◽

Cervical Carcinoma ◽

Cancer Detection ◽

Intraepithelial Neoplasia ◽

Feature Ranking ◽

High Grade

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Human Papillomavirus and Prognosis of Invasive Cervical Cancer: A Population-Based Study

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.7.1906 ◽

2001 ◽

Vol 19 (7) ◽

pp. 1906-1915 ◽

Cited By ~ 106

Author(s):

Stephen M. Schwartz ◽

Janet R. Daling ◽

Katherine A. Shera ◽

Margaret M. Madeleine ◽

Barbara McKnight ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Cervical Carcinoma ◽

Invasive Cervical Cancer ◽

Figo Stage ◽

Invasive Cervical Carcinoma ◽

Hpv 16 ◽

Stage Ib ◽

Increased Risk ◽

Hpv 18

PURPOSE: To determine the association between human papillomavirus (HPV) type and prognosis of patients with invasive cervical carcinoma.PATIENTS AND METHODS: Patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IB to IV cervical cancer between 1986 and 1997 while residents of three Washington State counties were included (n = 399). HPV typing was performed on paraffin-embedded tumor tissue using polymerase chain reaction methods. Patients were observed for a median of 50.8 months. Total mortality (TM) and cervical cancer–specific mortality (CCSM) were determined. Hazards ratios (HR) adjusted for age, stage, and histologic type were estimated using multivariable models.RESULTS: Eighty-six patients had HPV 18–related tumors and 210 patients had HPV 16–related tumors. Cumulative TM among patients with HPV 18–related tumors and among patients with HPV 16–related tumors were 33.7% and 27.6%, respectively; cumulative CCSM in these two groups were 26.7% and 18.1%, respectively. Compared with patients with HPV 16–related cancers, patients with HPV 18–related cancers were at increased risk for TM (HRTM, 2.2; 95% confidence interval [CI], 1.3 to 3.6) and CCSM (HRCCSM, 2.5; 95% CI, 1.4 to 4.4). The HPV18 associations were strongest for patients with FIGO stage IB or IIA disease (HRTM, 3.1; 95% CI, 2.3 to 4.2; and HRCCSM, 5.8; 95% CI, 3.9 to 8.7), whereas no associations were observed among patients with FIGO stage IIB to IV disease. Virtually identical associations were found in the subset of patients with squamous cell carcinoma (n = 219).CONCLUSION: HPV 18–related cervical carcinomas, particularly those diagnosed at an early stage, are associated with a poor prognosis. Elucidating the mechanism or mechanisms underlying this association could lead to new treatment approaches for patients with invasive cervical carcinoma.

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Survivin, a novel anti-apoptosis inhibitor, expression in uterine cervical cancer and relationship with prognostic factors

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200501000-00017 ◽

2005 ◽

Vol 15 (1) ◽

pp. 113-119

Author(s):

J.-P. Lee ◽

K.-H. Chang ◽

J.-H. Han ◽

H.-S. Ryu

Keyword(s):

Cervical Cancer ◽

Normal Control ◽

Statistical Significance ◽

Survivin Expression ◽

Intraepithelial Neoplasia ◽

Uterine Cervical Cancer ◽

Normal Control Group ◽

Control Group ◽

Cervical Intraepithelial Neoplasia Grade ◽

Prognostic Information

A novel inhibitor of apoptosis, Survivin, seems to be involved in the critical steps of cancer onset and progression and may be associated with unfavorable clinical outcome. We investigated the expression of Survivin in patients with cervical intraepithelial neoplasia grade 3 (CIN3) and uterine cervical cancer, to determine whether Survivin expression is related to poor prognosis. Fourteen cases of CIN3, 53 cases of invasive uterine cervical squamous cell carcinoma (SCC), and 11 cases of normal control group were analyzed retrospectively. Immunohistochemical staining and Western blot was performed with antihuman Survivin antibody and analyzed with respect to patient outcome. Survivin was significantly expressed in cervical cancer groups compared to the normal control group (P < 0.05). Significant Survivin expression was also noted in cancer patients with lesion size ≥4 cm, lymphovascular invasion, elevated SCC antigen levels, and no response to initial therapy. In more advanced stages, Survivin expression tended to increase but without statistical significance (P = 0.081). No association was noted between Survivin expression and survival rate (P = 0.1011). We conclude that Survivin expression provides some prognostic information regarding uterine cervical cancer, even though it was not correlated with survival. It could represent a possible new prognostic marker of uterine cervical SCC patients.

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

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010015856x ◽

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)

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PECULIARITIES OF PAPILLOMAVIRUS GENOTYPING IN PATIENTS WITH CERVICAL INTRAEPITHELIAL NEOPLASIA

Ulyanovsk Medico-biological Journal ◽

10.34014/2227-1848-2020-3-104-111 ◽

2020 ◽

pp. 104-111

Author(s):

N.A. Shmakova ◽

G.N. Chistyakova ◽

I.N. Kononova ◽

I.I. Remizova

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Viral Load ◽

Cervical Intraepithelial Neoplasia ◽

Intraepithelial Neoplasia ◽

Squamous Intraepithelial Lesions ◽

Hpv 16 ◽

The World ◽

Intraepithelial Lesions ◽

Hpv 18

Recently, there has been a steady growth of cervical cancer all over the world, especially in Russia. Patients with cervical cancer have become much younger. At the same time, the human papillomavirus is not only the main factor in the neoplastic process, but it is also one of the most common sexually transmitted infections in the world. The aim of the paper is to assess the prevalence and characteristics of human papillomavirus genotypes in patients with cervical intraepithelial neoplasia. Materials and Methods. During the periodic screening we examined 213 women of a reproductive age with HPV infection. All patients underwent liquid-based cytology and human papillomavirus genotyping by polymerase chain reaction. Results. We revealed that the prevalence of cervical intraepithelial neoplasia among women with papillomavirus infection was 80.3 % (n=171). According to human papillomavirus genotyping, HPV 16 (38 %) and HPV 33 (32 %) prevailed. We also observed positive high correlation between high-grade squamous intraepithelial lesions (HSIL) and HPV 18 (r=+0.759, p=0.001), a negative mean correlation between HPV 45 and low-grade squamous intraepithelial lesions (LSIL) (r=-0.643, p=0.002). A cohort of patients with severe intraepithelial cervical lesions demonstrated high viral load rates. Conclusion. According to the results obtained, we established the dominance of HPV 16 and HPV 33 genotypes in cervical intraepithelial neoplasia. There were significant differences between HSIL and LSIL patients with HPV 18 and HPV 45. There was also a correlation between an increase in the viral load with the severity of the pathological process. Keywords: human papillomavirus, intraepithelial cervical neoplasms, cervical cancer. В последние годы в мире, особенно в России, наблюдается неуклонный рост и «омолаживание» рака шейки матки. При этом вирус папилломы человека является не только основным фактором прогрессирования неопластического процесса, но и одной из наиболее распространенных инфекций, предаваемых половым путем, в мире. Цель. Оценить распространенность и характеристику генотипов папилломавирусной инфекции у пациенток с цервикальными интраэпителиальными неоплазиями. Материалы и методы. Проведено обследование 213 пациенток репродуктивного возраста с ВПЧ-инфекцией, пришедших на профилактический осмотр. Всем женщинам было выполнено цитологическое исследование жидкостным методом и генотипирование вируса папилломы человека методом полимеразной цепной реакции. Результаты. Распространенность цервикальных интраэпителиальных неоплазий среди женщин с папилломавирусной инфекцией составила 80,3 % (171 пациентка). Согласно данным генотипирования вируса папилломы человека превалировал 16-й (38 %) и 33-й типы (32 %). Выявлена положительная высокая корреляционная связь между цервикальными неоплазиями высокой степени онкогенного риска (HSIL) и 18-м типом ВПЧ-инфекции (r=+0,759 при р=0,001), отрицательная средняя корреляционная связь 45-го типа ВПЧ с низкой степенью онкогенного риска (LSIL) (r=-0,643 при р=0,002). Продемонстрированы высокие показатели вирусной нагрузки в когорте пациенток с тяжелыми внутриэпителиальными цервикальными поражениями. Выводы. По результатам полученных данных установлено доминирование 16-го и 33-го генотипов ВПЧ при цервикальных интраэпителиальных неоплазиях с наличием значимых различий между пациентами с HSIL и LSIL в отношении 18-го и 45-го типов, а также связь роста уровня вирусной нагрузки с увеличением степени тяжести патологического процесса. Ключевые слова: вирус папилломы человека, интраэпителиальные новообразования шейки матки, рак шейки матки.

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Effect of introducing human papillomavirus genotyping into real-world screening on cervical cancer screening in China: a retrospective population-based cohort study

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211010939 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110109

Author(s):

Binhua Dong ◽

Huachun Zou ◽

Xiaodan Mao ◽

Yingying Su ◽

Hangjing Gao ◽

...

Keyword(s):

Cervical Cancer ◽

Cohort Study ◽

Human Papillomavirus ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Cox Regression ◽

Intraepithelial Neoplasia ◽

Population Based ◽

Hpv Genotyping ◽

Cytology Screening

Background: China’s Fujian Cervical Pilot Project (FCPP) transitioned cervical cancer screening from high-risk human papillomavirus (HR-HPV) nongenotyping to genotyping. We investigated the clinical impact of this introduction, comparing performance indicators between HR-HPV genotyping combined with cytology screening (HR-HPV genotyping period) and the previous HR-HPV nongenotyping combined with cytology screening (HR-HPV nongenotyping period). Methods: A retrospective population-based cohort study was performed using data from the FCPP for China. We obtained data for the HR-HPV nongenotyping period from 1 January 2012 to 31 December 2013, and for the HR-HPV genotyping period from 1 January 2014 to 31 December 2016. Propensity score matching was used to match women from the two periods. Multivariable Cox regression was used to assess factors associated with cervical intraepithelial neoplasia of grade 2 or worse (CIN2+). The primary outcome was the incidence of CIN2+ in women aged ⩾25 years. Performance was assessed and included consistency, reach, effectiveness, adoption, implementation and cost. Results: Compared with HR-HPV nongenotyping period, in the HR-HPV genotyping period, more CIN2+ cases were identified at the initial screening (3.06% versus 2.32%; p < 0.001); the rate of colposcopy referral was higher (10.87% versus 6.64%; p < 0.001); and the hazard ratio of CIN2+ diagnosis was 1.64 (95% confidence interval, 1.43–1.88; p < 0.001) after controlling for health insurance status and age. The total costs of the first round of screening (US$66,609 versus US$65,226; p = 0.293) were similar during the two periods. Higher screening coverage (25.95% versus 25.19%; p = 0.007), higher compliance with age recommendations (92.70% versus 91.69%; p = 0.001), lower over-screening (4.92% versus 10.15%; p < 0.001), and reduced unqualified samples (cytology: 1.48% versus 1.73%, p = 0.099; HR-HPV: 0.57% versus 1.34%, p < 0.001) were observed in the HR-HPV genotyping period. Conclusions: Introduction of an HR-HPV genotyping assay in China could detect more CIN2+ lesions at earlier stages and improve programmatic indicators. Evidence suggests that the introduction of HR-HPV genotyping is likely to accelerate the elimination of cervical cancer in China.

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