scholarly journals Persistent High-Risk HPV Infection and Molecular Changes Related to the Development of Cervical Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Pablo Moreno-Acosta ◽  
Alfredo Romero-Rojas ◽  
Nicolas Vial ◽  
Antonio Huertas ◽  
Jinneth Acosta ◽  
...  

This article is a preliminary investigational study that is aimed at giving hints about the interesting biomarkers involved in the transition process from low-grade cervix lesion to invasive cervical cancer. Our study focuses on the risk factors and tumour molecular changes in one patient. First in 1986, she was diagnosed a preinvasive cervix lesion. Then, 16 years later, she was diagnosed an invasive cervical cancer. The 2002 diagnosis was a squamous cell carcinoma of the cervix, stage IIIB (FIGO), whereas in 1986, she had been diagnosed a high-grade squamous intraepithelial cervical lesion. Retrospectively, the analysis of samples of preneoplastic lesions and invasive cervical cancer confirmed the histopathological diagnoses and detected the presence of HPV type and HPV-16 variants, as well as the overexpression of proteins such as hTERT, IGF1Rα, IGF1Rβ, CAIX, and GLUT1. Finally, the Arg72Pro polymorphism was detected in TP53. The role of high-risk HPV and HPV-16 variants and of hTERT, IGF1Rα, IGF1Rβ, CAIX, and GLUT1 variations seemed confirmed in the development and progression of cervical cancer. As a result, analyzing the molecular changes in one and same tumour that progresses from a low-grade cervix lesion to invasive cervical cancer could provide valuable information in order to improve detection, diagnosis, and treatment in the future.

Author(s):  
NF Brusnigina ◽  
MA Makhova ◽  
OM Chernevskaya ◽  
KA Orlova ◽  
EA Kolesnikova ◽  
...  

The purpose of the study was to assess detection rates of human papillomavirus in cervical cancer cases of Nizhny Novgorod. Materials and methods. We used the real-time polymerase chain reaction (PCR) to test samples of mucosa lining of the cervical canal and/or transformation zone taken from 630 women with cervical dysplasia of different degrees and 107 incident cases of cervical cancer that did not undergo treatment. The detection and differentiation of 14 genotypes of high-risk human papillomaviruses (HPV) was carried out using the AmpliSens® HPV HCR-genotype-FRT PRC kit. Results. The overall infection rate of women with oncogenic human papillomaviruses was 41.8%. Among the genotypes, HPV 16 (39.2%), 18 (15.5%), 33 (16.6%), and 56 (11.9%) predominated. A high prevalence of oncogenic HPV was detected in the women with cervical intraepithelial neoplasia (58.1%) and cervical cancer (90%). The spectrum of genotypes in women with neoplasia of various degrees differed. In women with CIN II and CIN III, vaccine-preventable HPV genotypes (HPV 16 and 18) playing the leading role in the development of cervical cancer were the most frequent. The same genotypes dominated in the women with invasive cervical cancer. One oncogenic HPV genotype was usually found in the infected women (69%). The high-risk HPV infection was often combined with Ureaplasma ssp (49.3%), Mycoplasma hominis (20.1%), Cytomegalovirus (21.1%), and Herpes simplex I/II (18.2%) infections. Combinations of high-risk HPV with Chlamydia trachomatis and Herpes 6 were found in 8.3% and 5% of the cases, respectively. Conclusions. Our findings proved a wide prevalence of high carcinogenic risk HPV 16 and 18 genotypes, thus indicating the expediency of using Cervarix and Gardasil vaccines registered in the Russian Federation and containing antigens to these types of virus for specific prevention of the HPV infection.


2018 ◽  
Vol 19 (11) ◽  
pp. 3297 ◽  
Author(s):  
Wieke Kremer ◽  
Marjolein van Zummeren ◽  
Daniëlle Heideman ◽  
Birgit Lissenberg-Witte ◽  
Peter Snijders ◽  
...  

Data on human papillomavirus (HPV) type-specific cervical cancer risk in women living with human immunodeficiency virus (WLHIV) are needed to understand HPV–HIV interaction and to inform prevention programs for this population. We assessed high-risk HPV type-specific prevalence in cervical samples from 463 WLHIV from South Africa with different underlying, histologically confirmed stages of cervical disease. Secondly, we investigated DNA hypermethylation of host cell genes ASCL1, LHX8, and ST6GALNAC5, as markers of advanced cervical disease, in relation to type-specific HPV infection. Overall, HPV prevalence was 56% and positivity increased with severity of cervical disease: from 28.0% in cervical intraepithelial neoplasia (CIN) grade 1 or less (≤CIN1) to 100% in invasive cervical cancer (ICC). HPV16 was the most prevalent type, accounting for 9.9% of HPV-positive ≤CIN1, 14.3% of CIN2, 31.7% of CIN3, and 45.5% of ICC. HPV16 was significantly more associated with ICC and CIN3 than with ≤CIN1 (adjusted for age, ORMH 7.36 (95% CI 2.33–23.21) and 4.37 (95% CI 1.81–10.58), respectively), as opposed to non-16 high-risk HPV types. Methylation levels of ASCL1, LHX8, and ST6GALNAC5 in cervical scrapes of women with CIN3 or worse (CIN3+) associated with HPV16 were significantly higher compared with methylation levels in cervical scrapes of women with CIN3+ associated with non-16 high-risk HPV types (p-values 0.017, 0.019, and 0.026, respectively). When CIN3 and ICC were analysed separately, the same trend was observed, but the differences were not significant. Our results confirm the key role that HPV16 plays in uterine cervix carcinogenesis, and suggest that the evaluation of host cell gene methylation levels may monitor the progression of cervical neoplasms also in WLHIV.


2019 ◽  
Vol 7 (5) ◽  
pp. 338-344
Author(s):  
Miao Li ◽  
Qing-Fan Yang ◽  
Qian Cao ◽  
Jian Tang ◽  
Yu Gao ◽  
...  

Abstract Background and aim This cross-sectional study investigated the prevalence and risk factors of high-risk human papilloma virus (HPV) infection, especially types 16 and 18, and cervical neoplasia in female Inflammatory bowel disease (IBD) patients. Methods From July 2014 to January 2017, sexually active, female, Chinese IBD patients (21–60 years) and age-matched controls underwent cervical ThinPrep cytology testing (TCT) and high-risk HPV-DNA detection, and completed questionnaires about awareness of cervical cancer and HPV. Cervical dysplasia was categorized as cervical intraepithelial neoplasia (CIN) 1, 2 and 3. Results Of 124 IBD patients (30 ulcerative colitis and 94 Crohn’s disease), 17 (13.7%) had high-risk HPV among whom 9 (7.3%) had HPV 16/18 infection and 4 (3.2%) had cervical CIN (3 CIN 3, 1 CIN 1) by pathology. Among 372 controls, 33 (8.9%) had high-risk HPV and only 1 (0.3%) had HPV 16 infection. Cervical TCT detected atypical squamous cells of unknown significance in one control; no control had CIN. The HPV 16/18 infection rate and CIN prevalence were significantly higher in IBD patients than controls (both P < 0.001). The HPV-infection rate was higher in patients administered methotrexate [P = 0.005, odds ratio (95% confidence interval) 4.76 (1.471–15.402)] or more than two immunosuppressants [P = 0.013, odds ratio (95% confidence interval) 3.64 (1.255–10.562)]. Thiopurine, steroid, infliximab and disease behavior/location were not associated with HPV infection. Only 29.3% of patients had undergone cervical-cancer screening. Awareness of HPV infection and HPV-related cervical cancer was poor (28.2%). Conclusions Female IBD patients are at increased risk of high-risk HPV infection and cervical neoplasia, which may be associated with immunosuppressants. Education and routine follow-up with HPV-DNA testing and TCT are recommended, especially in female Chinese IBD patients.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 714
Author(s):  
Matthias Läsche ◽  
Horst Urban ◽  
Julia Gallwas ◽  
Carsten Gründker

Cervical cancer is responsible for around 5% of all human cancers worldwide. It develops almost exclusively from an unsolved, persistent infection of the squamocolumnar transformation zone between the endo- and ecto-cervix with various high-risk (HR) human papillomaviruses (HPVs). The decisive turning point on the way to persistent HPV infection and malignant transformation is an immune system weakened by pathobionts and oxidative stress and an injury to the cervical mucosa, often caused by sexual activities. Through these injury and healing processes, HPV viruses, hijacking activated keratinocytes, move into the basal layers of the cervical epithelium and then continue their development towards the distal prickle cell layer (Stratum spinosum). The microbial microenvironment of the cervical tissue determines the tissue homeostasis and the integrity of the protective mucous layer through the maintenance of a healthy immune and metabolic signalling. Pathological microorganisms and the resulting dysbiosis disturb this signalling. Thus, pathological inflammatory reactions occur, which manifest the HPV infection. About 90% of all women contract an HPV infection in the course of their lives. In about 10% of cases, the virus persists and cervical intra-epithelial neoplasia (CIN) develops. Approximately 1% of women with a high-risk HPV infection incur a cervical carcinoma after 10 to 20 years. In this non-systematic review article, we summarise how the sexually and microbial mediated pathogenesis of the cervix proceeds through aberrant immune and metabolism signalling via CIN to cervical carcinoma. We show how both the virus and the cancer benefit from the same changes in the immune and metabolic environment.


2021 ◽  
Vol 31 (Supplement_2) ◽  
Author(s):  
Ana Rita Fernandes Miranda da Costa ◽  
Cláudia Sousa ◽  
Erica Isidoro ◽  
Regina Silva ◽  
Cristiana Mourato

Abstract Background Persistent infection by high-risk Human Papillomavirus (hrHPV) are the major cause of cervical cancer. Studies report disparities in the incidence of infection and the various genotypes of this virus in different age groups, suggesting a higher frequency of hrHPV in young women and low-risk subtypes being predominant in older women. This study aimed to investigate the incidence and distribution of hrHPV genotypes in postmenopausal women as well as the correlation with the cytological findings. Methods 16 859 women, aged 50–64 years, performed cervical cancer screening test in Friuri Venezia Giulia region, Italy. The infection was evaluated by the Polymerase Chain Reaction methodology and the positive samples were evaluated by Liquid Based Cytology according to the Bethesda System from 2014. A statistical analysis was performed to study the molecular and cytological data of this population. Results hrHPV infection were found in 5.8% of the women and 78.3% of these were caused by hrHPV other than HPV16 and HPV18 (). Also, 65.7% of the positive samples were negative for intraepithelial lesion or malignancy while low grade squamous intraepithelial lesion was the most frequent (22.4%). There was an increase in the number of high-grade intraepithelial lesions in the presence of HPV16 compared to that recorded when this genotype was absent (20.8% vs. 8.5%). No cervical cancers were detected. Conclusions Infection with hrHPV is uncommon in postmenopausal women and it is mostly caused by subtypes less associated with the development of cervical cancer. Yet, HPV16 infection triggers the development of high-grade lesions.


2021 ◽  
Vol 9 ◽  
Author(s):  
Jacqueline Cortinhas Monteiro ◽  
Ricardo Roberto de Souza Fonseca ◽  
Tuane Carolina de Sousa Ferreira ◽  
Luana Lorena Silva Rodrigues ◽  
Andreza Reis Brasil da Silva ◽  
...  

Human papillomavirus (HPV) is the most common sexually transmitted infection in the world. Several studies have shown a higher prevalence of HPV infection in HIV-infected women. The aim of this study was to determine the prevalence and the genotype diversity of HPV infection in HIV-infected women. From April 2010 to December 2012 cervical specimens were collected from 169 HIV-infected women who screening for cervical cancer at Reference Unit in Belém. The detection of HPV infection was performed by nested PCR and HPV type was performed using a commercial system. The prevalence of HPV infection was 63.3%. Of the 47 genotyped samples, 40.4% was found positive for high risk-HPV 16 and 12.8% for high risk-HPV 52. HPV infection was predominant in the group of women with no incidence of cytological abnormalities and more prevalent in women of reproductive age, unmarried, low education level, and who reported use condoms during sexual intercourse. It was observed an association between HPV infection and independent variables, such as condom use, multiple sexual partners, and history of sexually transmitted diseases. High-risk types of HPV infection were prevalent in our study. Infection with multiple high-risk HPV genotypes may potentiate the development of cervical cancer in HIV-infected women.


2020 ◽  
Author(s):  
Yan Shen ◽  
Jing Xia ◽  
Hui hui Li ◽  
Yang Xu ◽  
San ping Xu

Abstract BackgroundThe incidence rate of cervical cancer is increasing yearly. The persistent infection of high-risk Human Papillomavirus (HPV) is the main factor leading to cervical cancer. HPV infection is double peak type. This study aimed at analyzing the HPV distribution characteristics, infection rate, and risk of age in pre- and postmenopausal women. So as to provide reference for the prevention of HPV infection and cervical cancer screening strategy.MethodsA retrospective analysis of 4614 women who underwent cervical cytology, and HPV examination from January 2018 to October 2019 at the healthcare department of Wuhan Union Hospital was done. We explored the characteristics and distribution of HPV infections around the menopause, then comparing the infection rate of HPV in postmenopause and over 65 years old, in order to analyze the influence of different ages on HPV infection.ResultsGenerally, the HPV infection rate was 13.10% (539 / 4115), whereby the high-risk subtype constituted 73.84% (398 / 539) of all positive cases. On the other hand, the HPV39 infection was more common in postmenopausal women; however, there was no significant difference in the distribution of the other types in the pre- and postmenopausal women (Insert p value). The first four subtypes were 52 / 53 / 58 / 16, respectively. The infection rate of HPV in patients with lower genital tract inflammation was significantly higher, P = 0.000, 95% CI: 1.911 (1.416, 2.580) compared with those without lower genital tract inflammation. The results further showed that there was no significant difference between pre- and postmenopausal women in terms of HPV infection rate, but more susceptible to high-risk HPV infection after the age of 65 (P = 0.041). Except for 40 years old to menopause, the infection rate of high-risk HPV in this age group was different from that in postmenopause(P = 0.023,0.729(0.555,0.957)), other age groups had no significant effect on high-risk HPV infection.ConclusionsIt was concluded that whether menopause has nothing to do with HPV infection. Moreover, the infection rate of high-risk HPV increases after 65 years of age; hence the cutoff screening age should be appropriately prolonged.Trial registration: Retrospectively registered.


2019 ◽  
Author(s):  
Li Song ◽  
Yuanjing Lyu ◽  
Ling Ding ◽  
Xiaoxue Li ◽  
Wen Gao ◽  
...  

Abstract Background: High-risk human papillomavirus (HR-HPV) infection is widely known as the major cause of cervical intraepithelial neoplasia (CIN) and cervical cancer and it’s characteristics vary greatly in different population. Women with abnormal cervical cytology could increase the risk of cervical cancer, however, HR-HPV infection characteristics in women with abnormal cervical cytology remains unclear. Methods: This study was based on baseline survey of the CIN Cohort established in Shanxi Province, China. A total number of 2300 women with cervical abnormalities were enrolled in this study. All participants gave informed consent and agreed to HPV and thinprepcytologic test (TCT). Each individual completed a questionnaire about characteristics related to HPV infection. Results: The overall prevalence of HR-HPV in 2300 women was 32.0%, and the proportion of single and multiple HR-HPV infections were 70.2% and 29.8% in HR-HPV infection women, respectively. The top five HR-HPV genotypes were ranked as HPV16, HPV58, HPV52, HPV53 and HPV51. The prevalence of HR-HPV in atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion and above(HSIL+) were 30.8%, 36.5% and 54.9%, respectively, showing an increasing trend with the severity of cervical cytology ( χ 2 trend =13.952; p <0.001). The women aged 35~45 years, with lower education level, less frequency of bathing, multiple gravidity, multiple parity, history of gynecological diseases and premenopausal women were prone to HR-HPV infection. Conclusions: We defined the characteristics related to HR-HPV infection in abnormal cervical cytology women, and provided an insight for the development and deeply research of HPV vaccine.


2014 ◽  
Vol 39 (2) ◽  
pp. 86-90 ◽  
Author(s):  
T Rahman ◽  
S Tabassum ◽  
M Jahan ◽  
A Nessa ◽  
Dr Ashrafunnessa

Human papillomavirus (HPV) high risk genotype infection and HPV viral load influences the development of invasive cervical cancer and cervical intra-epithelial neoplasia (CIN). HPV DNA testing for screening of cervical cancers may play a potential role in its early detection and management. The present study detected HPV DNA and estimated HPV viral load in different types of cervical lesions among Bangladeshi women. Using the Hybrid Capture 2 (HC2) assay, HPV DNA was tested among 68 women between 25-70 years of age. A total of 13 (19.1%) cases were positive for HPV DNA. The highest viral load (501 x 10³ copies/ml) was detected in a patient with invasive carcinoma, while the lowest viral load (105 x 10³ copies/ml) was detected from a case of chronic cervicitis. The mean viral load in CIN I was 119.25 x 10³±12.5 x 10³ copies/ml (range: 110 x 10³ - 137 x 10³) and 208.50 x 10³ ± 0.59 x 10³ copies/ml (range: 139 x 10³-305 x 10³) in CIN II / III. Interestingly, HPV DNA was detected from a patient with normal cytological findings. Our study observed a moderate presence of high-risk HPV genotypes among women with cervical lesions. The HPV viral load varied with the age of the patients and stage of cervical lesions. The HC2 assay is a promising tool for diagnosing high-risk HPV infection especially before cytology tests show any abnormality. DOI: http://dx.doi.org/10.3329/bmrcb.v39i2.19648 Bangladesh Med Res Counc Bull 2013; 39: 86-90


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