Association of HLA-G 3' UTR polymorphism and expression with the progression of cervical lesions in human papillomavirus 18 infections.
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ABSTRACT:
SUBMITTER: Xu HH
PROVIDER: S-EPMC6311041 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
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Association of HLA-G 3' UTR polymorphism and expression with the progression of cervical lesions in human papillomavirus 18 infections.
Xu Hui-Hui HH Zhang Xia X Zheng Hai-Hong HH Han Qiu-Yue QY Lin Ai-Fen AF Yan Wei-Hua WH
Infectious agents and cancer 20181229
<h4>Background</h4>Human leukocyte antigen (HLA)-G is an immune checkpoint molecule, which expression in cervical cancer cells enables them to escape immunosurveillance. To date, limited information has been published on the association of HLA-G genetic background in malignant cells with levels of HLA-G expression and the clinical outcome of patients.<h4>Methods</h4>We investigated the influence of the HLA-G <i>14 bp In/Del</i> (rs66554220) and + 3142<i>C/G</i> (rs1063320) polymorphisms in 130 c ...[more]
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Project description:BACKGROUND We studied the effect of APOBEC3G on persistent human papillomavirus (HPV) infection and the correlation between APOBEC3G polymorphism and HPV persistent infection and cervical disease progression in Uygur women in China. MATERIAL AND METHODS From January 2015 to December 2017, we enrolled 529 Uygur ethnic group patients with HPV infection. SIHA cells were transfected with APOBEC3G. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were used to detect mRNA and protein expression levels of APOBEC3G and HPV E6 and p53. Exon 3 of APOBEC3G was sequenced by first-generation sequencing. RESULTS The mRNA and protein expression levels of APOBEC3G in the cervical cancer group were significantly higher than in the cervical intraepithelial neoplasia (CIN) group (p<0.05). The mRNA and protein expression levels of APOBEC3G in the CIN group were significantly higher than in the non-cervical lesions group (p<0.05). The mRNA and protein expression levels of HPV E6 in SIHA cells transfected with APOBEC3G were significantly lower than in the control group and the no-load group (p<0.05), and the mRNA and protein expression levels of p53 were significantly higher than in the control group and the no-load group (p<0.05). There was a polymorphic locus rs5757465 on exon 3 of APOBEC3G in Uygur women, and this rare CC type was a risk factor for cervical lesions and cervical cancer (OR=3.714, 95%CI: 1.916-7.202, p<0.05). CONCLUSIONS APOBEC3G is involved in continuous HPV infection, cervical prelesions, and the development of cervical cancer, and the rare genotype (CC) of APOBEC3G may be one of the factors causing cervical lesions in Uygur women who have HPV infection.
| S-EPMC6761851 | biostudies-literature
Project description:BACKGROUND:Human papillomavirus vaccines prevent human papillomavirus infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an human papillomavirus-associated lesion is not fully understood. OBJECTIVES:To determine whether human papillomavirus-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions. STUDY DESIGN:We included 1711 women (18-25 years) with carcinogenic human papillomavirus infection and 311 women of similar age who underwent treatment for cervical precancer and who participated in a community-based trial of the AS04-adjuvanted human papillomavirus-16/18 virus-like particle vaccine. Participants were randomized (human papillomavirus or hepatitis A vaccine) and offered 3 vaccinations over 6 months. Follow-up included annual visits (more frequently if clinically indicated), referral to colposcopy of high-grade and persistent low-grade lesions, treatment by loop electrosurgical excisional procedure when clinically indicated, and cytologic and virologic follow-up after treatment. Among women with human papillomavirus infection at the time of vaccination, we considered type-specific viral clearance, and development of cytologic (squamous intraepithelial lesions) and histologic (cervical intraepithelial neoplasia) lesions. Among treated women, we considered single-time and persistent human papillomavirus infection, squamous intraepithelial lesions, and cervical intraepithelial neoplasia 2 or greater. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated. RESULTS:Median follow-up was 56.7 months (women with human papillomavirus infection) and 27.3 months (treated women). There was no evidence of vaccine efficacy to increase clearance of human papillomavirus infections or decrease incidence of cytologic/histologic abnormalities associated with human papillomavirus types present at enrollment. Vaccine efficacy for human papillomavirus 16/18 clearance and against human papillomavirus 16/18 progression from infection to cervical intraepithelial neoplasia 2 or greater were -5.4% (95% confidence interval -19,10) and 0.3% (95% confidence interval -69,41), respectively. Among treated women, 34.1% had oncogenic infection and 1.6% had cervical intraepithelial neoplasia 2 or greater detected after treatment, respectively, and of these 69.8% and 20.0% were the result of new infections. We observed no significant effect of vaccination on rates of infection/lesions after treatment. Vaccine efficacy estimates for human papillomavirus 16/18 associated persistent infection and cervical intraepithelial neoplasia 2 or greater after treatment were 34.7% (95% confidence interval -131, 82) and -211% (95% confidence interval -2901, 68), respectively. We observed evidence for a partial and nonsignificant protective effect of vaccination against new infections absent before treatment. For incident human papillomavirus 16/18, human papillomavirus 31/33/45, and oncogenic human papillomavirus infections post-treatment, vaccine efficacy estimates were 57.9% (95% confidence interval -43, 88), 72.9% (95% confidence interval 29, 90), and 36.7% (95% confidence interval 1.5, 59), respectively. CONCLUSION:We find no evidence for a vaccine effect on the fate of detectable human papillomavirus infections. We show that vaccination does not protect against infections/lesions after treatment. Evaluation of vaccine protection against new infections after treatment and resultant lesions warrants further consideration in future studies.
| S-EPMC4967374 | biostudies-literature
Project description:BackgroundHow vaginal infections such as bacterial vaginosis, Candida spp, and Trichomonas vaginalis affect persistence of human papillomavirus (HPV) infection is not well established. Our study aimed to evaluate the association between common vaginal infections and cervical non-HPV16/18 infection, as risk factors associated with persistence of nonvaccine HPV types will become increasingly relevant in the setting of HPV vaccination.MethodsWe performed an analysis in 2039 AS04-HPV16/18-vaccinated women enrolled in a phase II/III trial in China, who were HPV DNA negative at month 0 and 6 and had at least 1 subsequent follow-up visit. Vaginal infections were detected in liquid-based cytology according to the diagnostic criteria of the Bethesda System. Associations between vaginal infections and incident and 6-month persistent non-HPV16/18 infections in the cervix were evaluated using generalized estimating equations, adjusting for the age at initial vaccination, as well as HPV types in the persistence analysis.ResultsStudy visits with any vaginal infection had a statistically significant increased risk of incident non-HPV16/18 infection compared to those without vaginal infections (odds ratio [OR], 1.44 [95% confidence interval {CI}, 1.09-1.92]). However, vaginal infections were not associated with 6-month persistent non-HPV16/18 infection (OR, 1.02 [95% CI, .62-1.69]).ConclusionsOur study suggests that common vaginal infections are not associated with persistence of non-HPV16/18 infection among HPV16/18-vaccinated women.
| S-EPMC7982446 | biostudies-literature
Project description:BackgroundCervical cancer is caused by high-risk Human Papillomavirus (hr-HPV) infection associated with cofactors that has been analyzed as predictors of the remission or persistence of cytological abnormalities remission or persistence. These cofactors can be either environmental, epigenetic, or genetic. Polymorphism in genes of enzymes that act on one-carbon metabolism alter their activity and also may be associated with cervical carcinogenesis because they affect DNA synthesis and repair, and gene expression. Therefore, this study aimed to analyze the risk of persistence of pre-neoplastic cervical lesions according to genetic polymorphisms involved in one-carbon metabolism.MethodsOur sample consisted of 106 women, divided into two groups - Remission (n?=?60), i.e., with the presence of pre-neoplastic lesions at first meeting (T1) and normal cytology after 6 months of follow-up (T2), and Persistence (n?=?46), i.e., with the presence of pre-neoplastic lesions at T1 and T2. We obtained cervical samples for cytological analysis (T1 and T2), HPV detection (T1), and evaluation of polymorphism C667T of Methylenetetrahydrofolate Reductase (MTHFR C677T), A2756G of Methionine Synthase (MS A2756G), A66G of Methionine Synthase Reductase (MTRR A66G), double or triple 28?bp tandem repeat in 5'-untranslated enhanced region of Thymidylate Synthase (TSER), and 6?bp deletion at nucleotide 1494 in TS 3'-untranslated region (TS3'UTR). To analyze all genetic polymorphisms simultaneously, we calculated the Genetic Risk Score (GRS).ResultsWe observed no differences between the Remission and Persistence groups regarding the GRS. Also, there were no differences in the genotypic and allelic distribution of MTHFR C677T and MS A2756G polymorphisms. However, the risk of persistence was higher among women with the heterozygote genotype - ins/del [OR (IC95%): 3.22 (1.19-8.69), p?=?0.021], or the polymorphic genotype - del/del [OR (IC95%): 6.50 (1.71-24.70), p?=?0.006] of TS3'UTR.ConclusionsThe presence of the TS3'UTR polymorphism increased the risk of persistence of cervical abnormalities. This genetic variant could be a potential marker of cervical carcinogenesis and therefore assist the follow-up of women with persistent pre-neoplastic cervical lesions.
| S-EPMC7161242 | biostudies-literature
Project description:Change in the host and/or human papillomavirus (HPV) DNA methylation profile is probably one of the main factors responsible for the malignant progression of cervical lesions to cancer. To investigate those changes we studied 173 cervical samples with different grades of cervical lesion, from normal to cervical cancer. The methylation status of nine cellular gene promoters, CCNA1, CDH1, C13ORF18, DAPK1, HIC1, RARβ2, hTERT1, hTERT2 and TWIST1, was investigated by Methylation Specific Polymerase Chain Reaction (MSP). The methylation of HPV18 L1-gene was also investigated by MSP, while the methylated cytosines within four regions, L1, 5'LCR, enhancer, and promoter of the HPV16 genome covering 19 CpG sites were evaluated by bisulfite sequencing. Statistically significant methylation biomarkers distinguishing between cervical precursor lesions from normal cervix were primarily C13ORF18 and secondly CCNA1, and those distinguishing cervical cancer from normal or cervical precursor lesions were CCNA1, C13ORF18, hTERT1, hTERT2 and TWIST1. In addition, the methylation analysis of individual CpG sites of the HPV16 genome in different sample groups, notably the 7455 and 7694 sites, proved to be more important than the overall methylation frequency. The majority of HPV18 positive samples contained both methylated and unmethylated L1 gene, and samples with L1-gene methylated forms alone had better prognosis when correlated with the host cell gene promoters' methylation profiles. In conclusion, both cellular and viral methylation biomarkers should be used for monitoring cervical lesion progression to prevent invasive cervical cancer.
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Project description:BackgroundFactors that lead human papillomavirus (HPV) infections to persist and progress to cancer are not fully understood. We evaluated co-factors for acquisition, persistence, and progression of non-HPV-16/18 infections among HPV-vaccinated women.MethodsWe analyzed 2153 women aged 18-25 years randomized to the HPV-vaccine arm of the Costa Rica HPV Vaccine Trial. Women were HPV DNA negative for all types at baseline and followed for approximately 11 years. Generalized estimating equation methods were used to account for correlated observations. Time-dependent factors evaluated were age, sexual behavior, marital status, hormonally related factors, number of full-term pregnancies (FTPs), smoking behavior, and baseline body mass index.ResultsA total of 1777 incident oncogenic non-HPV-16/18 infections were detected in 12 292 visits (average, 0.14 infections/visit). Age and sexual behavior-related variables were associated with oncogenic non-HPV-16/18 acquisition. Twenty-six percent of incident infections persisted for ≥1 year. None of the factors evaluated were statistically associated with persistence of oncogenic non-HPV-16/18 infections. Risk of progression to Cervical Intraepithelial Neoplasia grade 2 or worst (CIN2+) increased with increasing age (P for trend = .001), injectable contraceptive use (relative risk, 2.61 [95% confidence interval, 1.19-5.73] ever vs never), and increasing FTPs (P for trend = .034).ConclusionsIn a cohort of HPV-16/18-vaccinated women, age and sexual behavior variables are associated with acquisition of oncogenic non-HPV-16/18 infections; no notable factors are associated with persistence of acquired infections; and age, parity, and hormonally related exposures are associated with progression to CIN2+.
| S-EPMC8496490 | biostudies-literature
Project description:Prevalence of different HPV genotypes is changing after HPV vaccination. The associated risks are needed for optimizing cervical cancer screening.To estimate HPV type-specific prevalence, odds ratio (OR), and positive predictive value (PPV) for cervical cytological abnormalities, we determined 41 different HPV genotypes in cervical samples from a population-based sample of 8351 women aged 18-51 years before HPV vaccination era (V501-033; NCT01077856).Prevalence of HPV16 was 4.9% (95% CI: 4.4-5.5) with the PPV for high-grade cytology 11.2%, and OR 11.9 (95% CI: 8.5-16.5). Carcinogenic HPVs included in the nonavalent vaccine (HPV16,18,31,33,45,52,58) had a population prevalence of 14.4% (95% CI: 13.5-15.4), with PPV of 8.0% (95% CI: 6.8-9.3) and OR 23.7 (95% CI: 16.0-63.5) for high-grade cytology. HPV types currently included in most screening tests, but not vaccinated against (HPV35,39,51,56,59,66,68) had a joint prevalence of 8.5% (95% CI: 7.8-9.2) with PPV of 4.4% (95% CI: 3.3-5.7) and OR of 2.9 (95% CI: 2.0-4.0) for high-grade cytology. The other 27 non-carcinogenic genotypes had a prevalence of 11.8%, PPV of 2.9% (95% CI:2.1-3.9), and OR 1.5 (95% CI: 1.1-2.2.) for high-grade cytology.These results suggest that HPV screening tests in the post-vaccination era might perform better if restricted to the HPV types in the nonavalent vaccine and screening for all 14 HPV types might result in suboptimal balance of harms and benefits.
| S-EPMC8018444 | biostudies-literature
Project description:Determining the causal attribution of human papillomavirus (HPV) genotypes to cervical disease is important to estimate the effect of HPV vaccination and to establish a type spectrum for HPV-based screening. We analyzed the prevalence of HPV infections and their attribution to cervical disease in a population of 1,670 women referred to colposcopy for abnormal cytology at the University of Oklahoma. HPV genotyping was performed from cytology specimens using the Linear Array assay that detects 37 HPV genotypes. We used different methods of type attribution to revised cervical disease categories. We found very high prevalence of multiple HPV infections with up to 14 genotypes detected in single specimens. In all disease categories except for cancers, there was a significant trend of having more infections at a younger age. We did not see type interactions in multiple genotype infections. HPV16 was the most frequent genotype at all disease categories. Based on different attribution strategies, the attribution of vaccine genotypes (6, 11, 16, 18) ranged from 50.5 to 67.3% in cancers (n = 107), from 25.6 to 74.8% in CIN3 (n = 305), from 15.2 to 52.2% in CIN2 (n = 427), and from 6.6 to 26.0% in <CIN2 (n = 708). In the HSIL cytology group (n = 651), attribution ranged from 26.1 to 64.7%. The attribution of vaccine types to HSIL was substantially higher compared to the lower cytology categories. The potential range of HPV genotype attribution is wide at the disease categories <CIN2 to CIN3. Genotyping from cervical lesions and analyzing viral oncogene expression can improve estimates of HPV genotype attribution.
| S-EPMC2755508 | biostudies-literature
Project description:Persistent high-risk human papillomavirus (HR-HPV) infections play a major role in the development of invasive cervical cancer (CC), and screening for such infections is in many countries the primary method of detecting and preventing CC. HPV typing can be used for triage and risk stratification of women with atypical squamous cells of undetermined significance (ASC-US)/low-grade cervical lesions (LSIL), though the current clinical practice in Mexico is to diagnose CC or its preceding conditions mainly via histology and HR-HPV detection. Additional information regarding these HPV infections, such as viral load and co-infecting agents, might also be useful for diagnosing, predicting, and evaluating the possible consequences of the infection and of its prevention by vaccination. The goal of this follow-up hospital case study was to determine if HPV types, multiple HPV infections, and viral loads were associated with infection persistence and the cervical lesion grade. A total of 294 cervical cytology samples drawn from patients with gynecological alterations were used in this study. HPV types were identified by real-time PCR DNA analysis. A subset of HPV-positive patients was reevaluated to identify persistent infections. We identified HPV types 16, 18, and 39 as the most prevalent. One hundred five of the patients (59%) were infected with more than one type of HPV. The types of HPV associated with multiple HPV infections were 16, 18, and 39. In the follow-up samples, 38% of patients had not cleared the initially detected HPV infection, and these were considered persistent. We found here an association between multiple HPV infections and high viral loads with and infection persistence. Our findings suggest there are benefits in ascertaining viral load and multiple HPV infections status of HR-HPV infections for predicting the risk of persistence, a requirement for developing CC. These findings contribute to our understanding of HPV epidemiology and may allow screening programs to better assess the cancer-developing risks associated with individual HR-HPV infections.
| S-EPMC7232502 | biostudies-literature
Project description:BackgroundIn the English pilot of primary cervical screening with high-risk human papillomavirus (HR-HPV), we exploited natural viral clearance over 24 months to minimise unnecessary referral of HR-HPV+ women with negative cytology. Three laboratories were permitted to use 16/18 genotyping to select women for referral at 12-month recall. We estimated the clinical impact of this early genotyping referral.MethodsThe observed numbers of women referred to colposcopy and with detected high-grade cervical intraepithelial neoplasia (CIN2+), and of women who did not attend early recall in the three laboratories were compared with those estimated to represent a situation without an early genotyping referral. The 95% confidence intervals (CI) for the differences between the protocols were calculated by using a parametric bootstrap.ResultsAmongst 127,238 screened women, 16,097 (13%) had HR-HPV infections. The genotyping protocol required 5.9% (95% CI: 4.4-7.7) additional colposcopies and led to a detection of 1.2% additional CIN2+ (95% CI: 0.6-2.0), while 2.3% (95% CI: 2.1-2.5) fewer HR-HPV+/cytology- women did not attend the early recall compared with the non-genotyping protocol.ConclusionsIn a screening programme with high quality of triage cytology and high adherence to early recall,16/18 genotyping of persistent HPV infections does not substantially increase CIN2+ detection.
| S-EPMC6738108 | biostudies-literature