scholarly journals HPV16-Related Cervical Cancers and Precancers Have Increased Levels of Host Cell DNA Methylation in Women Living with HIV

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.

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.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1576-1576
Author(s):  
Sally Nneoma Akarolo-Anthony ◽  
Celestine C. Ogbonna ◽  
Oluranti Ayotunde Famooto ◽  
Eileen O. Dareng ◽  
Maryam Al-Mujtaba ◽  
...  

1576 Background: The incidence of cervical cancer has remained stable in HIV+ women but the prevalence and multiplicity of high risk HPV (hrHPV) infection, a necessary cause of cervical cancer, appears different comparing HIV+ to HIV- women. Because this has not been well studied in Africa, we conducted this study to identify single and multiple hrHPV infection among HIV+ and HIV- women in Nigeria. Methods: We enrolled HIV+ and HIV- women presenting at our cervical cancer screening program in Abuja, Nigeria between April 2012 and August 2012. Using a nurse administered questionnaire, we collected information on demographic characteristics, risk factors of HPV infection and cervical exfoliated cells samples from all participants. We used Roche Linear Array HPV Genotyping Test to characterize the prevalent HPV according to manufacturer’s instruction and logistic regression models to estimate the association between HIV infection and the risk of high-risk HPV infection. Results: There were 278 participants, 40% (111) of whom were HIV negative, 54% (151) HIV positive and 6% (16) with HIV status unknown. Of these, 108 HIV+ women cases and 149 HIV- women controls were available for analysis. The mean ages (±SD) were 37.6 (±7.7) for HIV+ and 36.6 (±7.9) years for HIV- women (p-value = 0.34). Cases and controls had similar socio-demographic characteristics. Among HIV+ women, HPV35 (8.7%) and HPV56 (7.4%) were the most prevalent hrHPV, while HPV52 and HPV68 (2.8%, each) were the most prevalent among HIV- women. The age adjusted RR for prevalent hrHPV was 4.18 (95% CI 2.05 – 8.49, p-value <0.0001), comparing HIV+ to HIV- women. The multivariate RR for any HPV and multiple hrHPV was 3.75 (95% CI 2.08 – 6.73, p-value 0.01) and 6.6 (95% CI 1.49 – 29.64, p-value 0.01) respectively, comparing HIV+ to HIV- women, adjusted for age, and educational level. Conclusions: HIV infection was associated with increased risk of any HPV, hrHPV and multiple HPV infections. Oncogenic HPV types 35, 52, 56 and 68 may be more important risk factors for cervical pre-cancer and cancer among women in Africa. Polyvalent hrHPV vaccines meant for African populations should protect against HPV types other than 16 and 18.


2005 ◽  
Vol 16 (2) ◽  
pp. 83-91 ◽  
Author(s):  
François Coutlee ◽  
Danielle Rouleau ◽  
Alex Ferenczy ◽  
Eduardo Franco

Human papillomaviruses (HPVs) are the etiological agents of several genital cancers, including cancer of the uterine cervix. The detection of HPV infection in genital samples may increase the sensitivity of primary and secondary screenings of cervical cancer. HPV testing may also improve the specificity of screening programs, resulting in the avoidance of overtreatment and cost savings for confirmatory procedures. The major determinants of clinical progression of HPV infection include persistence of HPV infection, involvement of high-risk HPV types, high HPV viral load, integration of viral DNA and presence of several potential cofactors. Signal amplification HPV-DNA detection techniques (Hybrid Capture II, Digene Corporation, USA) are standardized, commercially available, and capable of detecting several high-risk HPV types. They also increase the sensitivity of screening for high-grade lesions in combination with cytology. The sensitivity of these techniques to detect high-grade lesions is higher than that of cytology, but the referral rate for colposcopy is greater. These techniques are approved for the triage to colposcopy of women with cervical smears interpreted as atypical squamous cells of undetermined significance. Triage and screening for cervical cancer using HPV will probably be restricted to women aged 30 years or older because of the high prevalence of infection in younger women. Amplification techniques are ideal for epidemiological studies because they minimize the misclassification of HPV infection status. These techniques can detect low HPV burden infections. Consensus primers amplify most genital types in one reaction, and the reverse hybridization of amplicons with type-specific probes allows for the typing of HPV-positive samples. Consensus PCR assays are currently under evaluation for diagnostic purposes. HPV testing is currently implemented for the clinical management of women.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
E Mastora ◽  
A Zikopoulos ◽  
A Galani ◽  
I Georgiou ◽  
K Zikopoulos

Abstract Study question A comparison between L1 gene and LCR region methylation status of HPV16 and HPV18 viruses in subfertile women, investigating HPV methylation pattern in cervical cancer and asymptomatic HPV infection. Summary answer CpG methylation was more frequent in L1 gene compared to LCR in both HPV types. Methylation levels were associated with the grade of cervical dysplasia. What is known already HPV infection is a common sexually transmitted disease, related to genital warts and cancer. DNA methylation as a dynamic and strictly controlled process can be involved in numerous cellular processes, cell differentiation, gene expression regulation and genome reprogramming. Human pappiloma virus genome epigenetic alterations may play a key role in HPV life cycle as well as in the oncogenic process in general. However, whether the prevalence of high risk HPV is correlated with female infertility, has yet to be elucidated. Study design, size, duration From January 2015 to December 2019, about 2505 infertile couples were referred to the Human Reproduction Unit of Ioannina University Hospital. A total of 212 clinical and laboratory data from female partners were included in the study. Participants/materials, setting, methods Cervical smears were studied for HPV DNA methylation. CpG methylation was compared among L1 gene and LCR region in both HPV types. A bisulfite modification assay followed by DNA amplification and sequencing was performed to analyse HPV16 and HPV18 genome. Main results and the role of chance In HPV16 types, L1 gene and promoter region indicated high methylation levels in cervical cancer cases. LCR regions methylation levels ranged from 0,5% to 24,2% in asymptomatic HPV16 infection or cervical intraepithelial neoplasia and cervical cancer, respectively. As for L1 gene, the differences between asymptomatic HPV16 infection and cervical cancer cases were statistically significant (P = 0.003). In HPV18 types, L1 gene was methylated in cervical intraepithelial neoplasia and cervical cancer cases. Promoter region methylation levels were high in cervical cancer cases while LCR region methylation levels were low. Limitations, reasons for caution Main limitation is the relatively small size of the collected samples. Wider implications of the findings: HPV genome investigation, as for methylation status, may lead to better understanding and earlier diagnostics of cervical pathology in infertile population. These observations point out the importance of fertility preservation in women at high risk for cervical neoplasia. Trial registration number Not applicable


1994 ◽  
Vol 5 (3) ◽  
pp. 189-193 ◽  
Author(s):  
Awa Coll Seek ◽  
Mama Awa Faye ◽  
Cathy W Critchlow ◽  
Adia Diack Mbaye ◽  
Jane Kuypers ◽  
...  

Studies in various regions of the world have shown that women infected with HIV-1 are at increased risk for cervical human papillomavirus (HPV) infection as well as for cervical cancer precursor lesions. HIV infection and cervical cancer are both widespread in West Africa, but little is known about the relationship between HPV and HIV-2, which is the predominant type of HIV in the general population of many West African countries. To address this issue, we collected cervical samples for cytology and HPV analysis from 93 women presenting to the University of Dakar Infectious Disease Service (18 women with HIV-1 infection, 17 with HIV-2 infection, and 58 HIV seronegative controls). Compared to those without HIV infection, HIV seropositive women were 13.1 (95% CI = 2.4, 128) and 11.0 (95% CI = 3.5, 35.8) times more likely to have HPV detected using Southern transfer hybridization (STH) and the polymerase chain reaction (PCR) respectively. Detection of high and intermediate risk HPV types were significantly associated with HIV-1 and HIV-2 infection. Among HPV positive women, those with, as compared to those without HIV infection were more likely to harbour high risk HPV types (OR = 9.2, 95% CI = 0.97, 433). HIV-1 and HIV-2 seropositive women were 23.3 (95% CI = 2.9, 209) and 9.3 (95% CI = 1.1, 79) times more likely to have a cytological diagnosis of dysplasia, respectively, than were HIV seronegative women. Biopsy-proven CIN 3 was found in one woman with HIV-1 and invasive cancer was found in one woman with HIV-2. It remains to be seen whether HIV-1 and HIV-2 will confer similar risks of development of CIN 2–3 and potentially of invasive cervical cancer.


2018 ◽  
Vol 7 (1) ◽  
pp. 12-17 ◽  
Author(s):  
Ting Miao

Abstract Persistent infection by human papillomavirus (HPV) is an important factor causing cervical cancer. In recent years, infection with multiple HPV types has been confirmed in various studies. High-risk HPV 16 and 18 and low-risk HPV 6 are the most common causes of multitype HPV infection. Infection with multiple types of HPV, which results from individual susceptibility, is crucial in tumor susceptibility. This paper summarizes the common types of multiple HPV infection to enable further research on the relationship between HPV and tumor susceptibility.


2017 ◽  
pp. 99-103
Author(s):  
Van Bao Thang Phan ◽  
Hoang Bach Nguyen ◽  
Van Thanh Nguyen ◽  
Thi Nhu Hoa Tran ◽  
Viet Quynh Tram Ngo

Introduction: Infection with HPV is the main cause of cervical cancer. Determining HPV infection and the types of HPV plays an important role in diagnosis, treatment and prognosis of cervicitis/cervical cancer. Aims: Determining proportion of high-risk HPV types and the occurrence of coinfection with multiple HPV types. Methods: 177 women with cervicitis or abnormal Pap smear result were enrolled in the study. Performing the real-time PCR for detecting HPV and the reverse DOT-BLOT assay for determining type of HPV in cases of positive PCR. Results: 7 types of high-risk HPV was dectected, the majority of these types were HPV type 18 (74.6%) and HPV type 16 (37.6%); the proportion of infection with only one type of HPV was 30.4% and coinfection with multiple HPV types was higher (69.6%), the coinfected cases with 2 and 3 types were dominated (32.2% and 20.3%, respectively) and the coinfected cases with 4 and 5 types were rare. Conclusion: Use of the real-time PCR and reverse DOT-BLOT assay can determine the high-risk HPV types and the occurrence of coinfection with multiple HPV types. Key words: HPV type, Reverse DOT-BLOT, real-time PCR,PCR, cervical cancer


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