scholarly journals Comprehensive genomic variation profiling of cervical intraepithelial neoplasia and cervical cancer identifies potential targets for cervical cancer early warning

2018 ◽  
Vol 56 (3) ◽  
pp. 186-194 ◽  
Author(s):  
Jian Huang ◽  
Zhaoyang Qian ◽  
Yuhua Gong ◽  
Yanzhou Wang ◽  
Yanfang Guan ◽  
...  

BackgroundTo better understand the pathogenesis of cervical cancer (CC), we systematically analysed the genomic variation and human papillomavirus (HPV) integration profiles of cervical intraepithelial neoplasia (CIN) and CC.MethodsWe performed whole-genome sequencing or whole-exome sequencing of 102 tumour-normal pairs and human papillomavirus probe capture sequencing of 45 CCs, 44 CIN samples and 25 normal cervical samples, and constructed strict integrated workflow of genomic analysis.ResultsMutational analysis identified eight significantly mutated genes in CC including four genes (FAT1, MLL3, MLL2 and FADD), which have not previously been reported in CC. Targetable alterations were identified in 55.9% of patients. In addition, HPV integration breakpoints occurred in 97.8% of the CC samples, 70.5% of the CIN samples and 42.8% of the normal cervical samples with HPV infection. Integrations of high-risk HPV strains in CCs, including HPV16, 18, 33 and 58, also occurred in the CIN samples. Moreover, gene mutations were detected in 52% of the CIN specimens, and 54.8% of these mutations occurred in genes that also mutated in CCs.ConclusionOur results lay the foundation for a deep understanding of the molecular mechanisms and finding new diagnostic and therapeutic targets of CC.

2017 ◽  
Vol 158 (31) ◽  
pp. 1213-1221 ◽  
Author(s):  
Zoltán Szentirmay ◽  
Zsuzsa Veleczki ◽  
Miklós Kásler

Abstract: Introduction: Persistent infection of human papillomavirus is known to cause cervical intraepithelial neoplasia or cancer in the cervix uteri and other HPV-associated cancers in different localization. Based on epidemiological and biological data, principally the high risk HPV is responsible for development of cervical these cancers. However, we have no information about the frequently distribution of different HPV types and what is the correlation between the HPV types and cytological diagnosis in cervical intraepithelial neoplasia (CIN). Aim: In this paper, we are going to present new data involving incidence and mortality of HPV-associated cancers during the period of 2009–2015 in Hungary. We are also going to investigate the correlation of cervical cytological diagnosis and HPV typing, and the preventive effect of HPV vaccination. Method: The epidemiological data spring from the National Cancer Registry. HPV typing was performed by Linear Array HPV Genotyping Test. Simultaneous cytological diagnosis and HPV typing was carried out on 2048 cytological samples collected in period of 2009–2016. Results: According to the epidemiologic data, the most frequently occurring HPV-associated cancer is the laryngeal carcinoma in man, and the cervical cancer in woman in Hungary. During the 2009–2015 time intervals, the frequency distribution of head and neck cancers was not changed in man, but the incidence of tongue root squamous cell carcinomas was gradually increasing in woman. We have defined the clinical significance of single and simultaneously multiple HPV infection and have investigated the correlation of the HPV frequency distribution and cytological diagnosis in CIN. It was found that in the cytological negativity of probably/possibly carcinogen pHR-HPV group classified by IACR was much more frequent as in HR-HPV group (56% versus 47%). The presence of simultaneous multiplex HPV infection betokens an increased cancer risk. According to the international publications, the ratio of HPV16 just twice as big as in cervical cancer, what we found in CIN (60% versus 30%). The frequency order of the HPV18 is 2nd in cancer, and 9th in CIN. Comparing the frequency distribution of HR/pHR-HPVs in cervical cancer and CIN, the HR-HPV35 is very rarely occurring in CIN, the pHR-HPV56, 66, and 73 is more frequently seen in CIN as in carcinoma. Appreciated the preventive value of anti-HPV vaccines, we have found a significant differences in group with 1 HPV/sample and in group with more than 1 HPV/sample. Conclusion: The frequency distribution of tongue root squamous cell carcinoma and cervical cancer was gradually increasing in woman. The overall preventive effect of 9-valent vaccine is 80.3%. This preventive value should be higher because of the transformation ability of the different HPV types is not same. Out of consideration for HPV incidence in cancer, the preventive effect of 9-valent or 4-valent vaccines might reach to 93% or 73%. However, the pHR-HPVs are biologically active, it is not sufficient for the inclusion of these HPV types into population-wide HPV-DNA based cervical screening programs. Orv Hetil. 2017; 158(31): 1213–1221.


Author(s):  
Min Feng ◽  
Rufei Duan ◽  
Yang Gao ◽  
Han Zhang ◽  
Youlin Qiao ◽  
...  

Given that only a small percentage of human papillomavirus (HPV)-positive women develop cancer, HPV is necessary but insufficient for carcinogenesis. Mucosally transmitted viral cofactors appear to contribute to HPV-related cervical cancer, such as Epstein-Barr virus (EBV), but previous studies have shown inconsistent outcomes. The exact role of EBV in cervical cancer remains unclear, and more studies are needed to determine its involvement. In this study, we describe the prevalence of EBV and HPV coinfection in HIV-positive women and explore how abnormal host immune status induced by viral coinfections modulates epithelial gene expression. We found a significant correlation between EBV-HPV coinfection and the incidence of high-grade cervical intraepithelial neoplasia (CIN2+). RNA sequencing indicated that CIN tissues coinfected with EBV and HPV led to significant changes in the gene expression of epithelial differentiation and development compared to normal tissues with HPV infection alone. In particular, several differentially expressed genes (DEGs) are closely associated with cancer, such as CACNG4, which was confirmed to be upregulated at both the mRNA and protein levels. Therefore, these findings provide some evidence that EBV may act as a cofactor or mediator in HPV-related cervical cancer. Specific genes or proteins, such as CACNG4, may serve as biomarkers that can risk stratify patients based on pathological changes in the cervix.


Author(s):  
Kun Lee ◽  
Jingyi Si ◽  
Ricai Han ◽  
Wei Zhang ◽  
Bingbing Tan ◽  
...  

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)


Author(s):  
N.A. Shmakova ◽  
G.N. Chistyakova ◽  
I.N. Kononova ◽  
I.I. Remizova

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.


2018 ◽  
Vol 7 (11) ◽  
pp. 5655-5664 ◽  
Author(s):  
Yingji Jin ◽  
Jae Woong Choi ◽  
Hyoung Jin Kim ◽  
Jamel Eddouzi ◽  
Seung Cheol Kim ◽  
...  

2004 ◽  
Vol 74 (1) ◽  
pp. 117-126 ◽  
Author(s):  
Maria Lina Tornesello ◽  
Maria Luisa Duraturo ◽  
Immacolata Salatiello ◽  
Luigi Buonaguro ◽  
Simona Losito ◽  
...  

GYNECOLOGY ◽  
2021 ◽  
Vol 23 (2) ◽  
pp. 125-130
Author(s):  
Yuliya E. Dobrokhotova ◽  
Ekaterina I. Borovkova

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.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yang Liu ◽  
Pianping Fan ◽  
Yingying Yang ◽  
Changjun Xu ◽  
Yajuan Huang ◽  
...  

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.


2011 ◽  
Vol 83 (6) ◽  
pp. 1034-1041 ◽  
Author(s):  
François Coutlée ◽  
Samuel Ratnam ◽  
Agnihotram V. Ramanakumar ◽  
Ralph R. Insinga ◽  
James Bentley ◽  
...  

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