Dataset Information

Correlation of APOBEC3G Polymorphism with Human Papillomavirus (HPV) Persistent Infection and Progression of Cervical Lesions.

ABSTRACT: 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.

SUBMITTER: Sui S

PROVIDER: S-EPMC6761851 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Correlation of APOBEC3G Polymorphism with Human Papillomavirus (HPV) Persistent Infection and Progression of Cervical Lesions.

Sui Shuang S Chen Hongxiang H Han Lili L Wang Lin L Niyazi Mayineur M Zhu Kaichun K

Medical science monitor : international medical journal of experimental and clinical research 20190917

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 detec ...[more]

PMID: 31527570

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Project description:BACKGROUND:Genetic factors may influence the susceptibility to high-risk (hr) human papillomavirus (HPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence. METHODS:Participants were 517 Nigerian women evaluated at baseline and 6?months follow-up visits for HPV. HPV was characterized using SPF10/LiPA25. hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done for hrHPV infection (125 cases/392 controls) and for persistent hrHPV infection (51 cases/355 controls) under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes. RESULTS:The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. No single variant reached genome-wide significance (p?<?5 X 10-?8). The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p?=?1.43?×?10-?6). The top variants associated with cervical hrHPV persistence were in DAP (OR: 6.86, p?=?7.15?×?10-?8), NR5A2 (OR: 3.65, p?=?2.03?×?10-?7) and MIR365-2 (OR: 7.71, p?=?2.63?×?10-?7) gene regions. CONCLUSIONS:This exploratory GWAS yielded suggestive candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.

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.

Project description:Few studies have been conducted on the relationship between metabolic syndrome (MetS) and cervical human papillomavirus (HPV) incidence and persistent infection. We performed a prospective cohort study including 8598 female employees in Hunan, China. First, the subjects were stratified into HPV-negative (N = 7282) and HPV-positive (N = 1316) subgroups, according to the results of an HPV DNA test at baseline. Second, comparisons of the risks of HPV incident and persistent infection between MetS-positive (exposed) and MetS-negative (unexposed) groups were conducted among the HPV-negative and -positive subgroups, respectively. There were 976 (11.39%) subjects diagnosed with MetS and 1316 subjects diagnosed with HPV infection at baseline. The 12-month cumulative incidence of any type of HPV and high-risk type HPV were 7.28% (530/7282) and 6.26% (456/7282), respectively. Obesity was a modifier of the association between MetS and HPV incident infection. As long as obesity presented, MetS and hypertriglyceridemia were significantly associated with an increased risk of HPV incident infection (any-type or high-risk type) (adjusted risk ratios (RR) were 2.88 (95% confidence interval (CI): 1.16, 7.19) and 3.29 (95% CI: 1.47, 7.38), respectively). Among those infected with HPV at baseline, the 12-month type-specific persistence rates were 51.67% and 53.38% for any-type and high-risk type HPV, respectively. No interaction was found between obesity and MetS with regard to the risk of HPV persistence. After adjustment for confounding factors, MetS was still associated with increased risk of any-type HPV persistence (RRadj = 1.21, 95% CI: 1.05, 1.41) and high-risk type HPV persistence (RRadj = 1.25, 95% CI: 1.09, 1.46). No single metabolic component was associated with the risk of HPV persistence. The prevalence of MetS was 11.39% among the Hunan female occupational population. MetS was associated with an increased risk of persistent cervical HPV infection and also with an increased risk of HPV incident infection when obesity presented as well.

Project description:ObjectiveTo study the outcome of human papillomavirus (HPV) infection in women with cervical pathology results of non-cervical intraepithelial neoplasia (CIN) or cervical cancer and positive high-risk HPV test, as well as analyze the associated risk factors affecting the outcome of infection.MethodsTo investigate the outcome of high-risk (HR)-HPV infection in the female genital tract and analyze the associated risk factors affecting their outcome, a total of 196 women with positive HR-HPV test results and non-CIN or cervical cancer cervical pathology results were selected for follow-up at the Cervical Disease Clinic of the Obstetrics and Gynecology Hospital, Zhejiang University School of Medicine from January 2017 to March 2020. The follow-up interval was every 6 months, and both cervical cytology (TCT) and HR-HPV testing were performed at each follow-up visit. If the cervical cytology results were normal upon recheck and the HR-HPV test was negative, the woman was considered to be cleared of the HPV infection and was entered into the routine cervical screening population. When the repeat HR-HPV test remained positive after 6 months, the woman was defined as having a persistent HR-HPV infection. If HR-HPV persisted but the TCT results were normal, follow-up was continued. If HR-HPV persisted and the TCT results were abnormal, a colposcopy-guided biopsy was performed immediately. In this situation, if the histological results were still non-CIN or cervical cancer, the follow-up was continued. If the histological results confirmed the development of CIN or invasive cancer, then enter another study follow-up to further track its development and outcome, and the woman commenced the treatment process. The HPV infection clearance time was analyzed by the Kaplan-Meier method, and the comparison of the HPV clearance rate and infection clearance time between each of the different groups was performed using aχ2 test or Fisher's exact test, as appropriate. After the univariate analysis, several significant factors were included in the Cox model and independent risk factors were analyzed.ResultsA total of 163 women were enrolled in this study. The median age was 40.0 years (22-67 years) and the median follow-up time was 11.5 months (6-31 months). The spontaneous clearance rate of HR-HPV infection was 51.5%, and the median time to viral clearance was 14.5 months. Age and the initial viral load were high risk factors affecting the spontaneous clearance of HR-HPV infection. The factors significantly associated with HPV clearance rate and time to HPV clearance consisted of menopause and full-term delivery (P < 0.05).ConclusionsIn women with normal or low-grade lesions on the cell smear, the spontaneous clearance rate of HR-HPV infection was 51.5% and the time to clearance was 14.5 months. Age and the initial viral load were independent associated factors affecting the spontaneous clearance of HR-HPV infection in the female genital tract. These findings suggest that non-young women or those with high viral loads have a higher rate of persistent HR-HPV infection. Thus, intensive screening should be recommended.

Dataset Information

Correlation of APOBEC3G Polymorphism with Human Papillomavirus (HPV) Persistent Infection and Progression of Cervical Lesions.

Publications

Correlation of APOBEC3G Polymorphism with Human Papillomavirus (HPV) Persistent Infection and Progression of Cervical Lesions.

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