Whole-Genome Analysis of Human Papillomavirus Type 16 Prevalent in Japanese Women with or without Cervical Lesions.
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ABSTRACT:
SUBMITTER: Hirose Y
PROVIDER: S-EPMC6520816 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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Project description:BackgroundHuman papillomavirus (HPV) type 67 is phylogenetically classified into Alphapapillomavirus species 9 (alpha-9) together with other carcinogenic types (HPV16, 31, 33, 35, 52 and 58), but is the only alpha-9 type defined as possibly carcinogenic. This study aimed to determine whole-genome sequences of HPV67 isolated from Japanese women with cervical cancer or cervical intraepithelial neoplasia (CIN) to better understand the genetic basis of the oncogenic potential of HPV67.MethodsTotal cellular DNA isolated from cervical exfoliated cells that were single positive for HPV67 (invasive cervical cancer, n = 2; CIN3, n = 6; CIN 2, n = 1; CIN1, n = 2; the normal cervix, n = 1) was subjected to PCR to amplify HPV67 DNA, followed by next generation sequencing to determine the complete viral genome sequences. Variant lineages/sublineages were assigned through viral whole-genome phylogenetic analysis. The transcriptional activity of the virus early promoter was assessed by luciferase reporter assays in cervical cancer cell lines.ResultsPhylogenetic analyses of HPV67 genomes from Japan (n = 12) revealed that 11 belonged to lineage A (sublineage A1, n = 9; sublineage A2, n = 2) and one belonged to lineage B. All cancer cases contained sublineage A1 variants, and one of these contained an in-frame deletion in the E2 gene. The long control region of the HPV67 genome did not induce transcription from the virus early promoter in HeLa cells, but showed weak transcriptional activity in CaSki cells.ConclusionsThe single detection of HPV67 in cervical cancer and precancer specimens strongly suggests the carcinogenic potential of this rare genotype. The phylogenetic analysis indicates a predominance of lineage A variants among HPV67 infections in Japan. Since only 23 complete genome sequences of HPV67 had been obtained until now, the newly determined genome sequences in this study are expected to contribute to further functional and evolutionary studies on the genetic diversity of HPV67.
| S-EPMC9547447 | biostudies-literature
Project description:BACKGROUND: Human Papillomavirus (HPV) high-risk (HR) types are the causal factor for cervical cancer and premalignant dysplasia. Data on frequency of HPV types provide a basis to design and evaluate HPV prevention programs. Taking into account the heterogeneity of HPV types across and within populations this study aims to access the HPV frequency in Brazilian women. RESULTS: We identified 24 different types of HPV, including a Betapapillomavirus and a likely new type, previously reported, from 132 women positive for the virus analysed by Hybrid Capture II assay. These women were infected by a single or multiple HPV types and 142 HPV strains were identified. HR types were found in 75% of women and HPV types 16, 18, 45, 58, and 66 had the highest frequency. Significant differences in frequency of HR HPV types were found for presence of cervical lesions, and for different HPV species and women age. CONCLUSIONS: Compared with previous studies in Brazil, our data indicated differences in frequency and HPV type diversity, a significant association of other HR-types but HPV16 and 18 and cervical lesions, and a trend for distinct distribution of HPV types by age.
| S-EPMC3024957 | biostudies-literature
Project description:BackgroundIncreasing evidence suggests that human papillomavirus (HPV) intratype variants (specific lineages and sublineages) are associated with pathogenesis and progression from HPV infection to persistence and the development of cervical cancer.ObjectivesThis study aimed to verify the prevalence of HPV infection and distribution of HPV types and HPV16 variants in southern Brazil in women with normal cytology or intraepithelial lesions.MethodsHPV typing was determined by L1 gene sequencing. To identify HPV16 variants, the LCR and E6 regions were sequenced, and characteristic single nucleotide variants were identified.FindingsA total of 445 samples were studied, with 355 from cervical scrapes and 90 from cervical biopsies. HPV was detected in 24% and 91% of these samples, respectively. The most prevalent HPV types observed were 16 (cervical, 24%; biopsies, 57%) and 58 (cervical, 12%; biopsies, 12%). Seventy-five percent of the HPV16-positive samples were classified into lineages, with 88% defined as lineage A, 10% as lineage D, and 2% as lineage B.Main conclusionsThis study identified a high frequency of European and North American HPV16 lineages, consistent with the genetic background of the human population in southern Brazil.
| S-EPMC5452486 | biostudies-literature
Project description:BackgroundHuman 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.ObjectivesTo 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 designWe 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.ResultsMedian 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.ConclusionWe 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:AimTo analyze the distribution of high-risk human papillomavirus (HR-HPV) genotypes and the diversity of HPV-16 genomic variants in Croatian women with high-grade squamous intraepithelial lesions (HSIL) and cervical carcinoma.MethodsTissue biopsy specimens were obtained from 324 women with histopathologically confirmed HSIL or cervical carcinoma, 5 women with low-grade SIL, and 49 women with negative histopathology. HR-HPV DNA was detected with Ampliquality HPV-type nucleic-acid hybridization assay, which identifies 29 different HPV genotypes. HPV-16 genomic variants were analyzed by an in-house sequencing.ResultsThe most common HPV type in women with HSIL was HPV-16, detected in 127/219 (57.9%) specimens. HPV-16 was also the dominant type in squamous cell cervical carcinoma (46/69 or 66.7%) and in adenocarcinoma (18/36 or 50.0%). Out of 378 patients, 360 had HR-HPV (282 single infections and 79 multiple infections), 3 (0.8%) patients had low-risk HPV, and 15 (4%) tested negative. HPV-16 variants were determined in 130 HPV-16 positive specimens, including 74 HSIL and 46 carcinoma specimens. In HSIL specimens, 41 distinct variants were found, 98.6% belonging to the European branch and 1.4% belonging to the African branch. In cervical carcinoma specimens, 95% isolates grouped in 41 variants belonging to the European branch, one isolate (2.5%) belonged to the North American, and one (2.5%) to the Asian-American branch.ConclusionHPV-16, mainly belonging to the European branch, was the most frequent HPV genotype in women from Croatia with histologically confirmed HSIL and cervical cancer.
| S-EPMC7976879 | biostudies-literature
Project description:Human papillomavirus type 16 (HPV16), a member of the Papillomaviridae family, is the primary etiological agent of cervical cancer. Here, we report the complete genome sequences of four HPV16 Asian American variants and four European variants, isolated from cervical biopsies and scrapings in India.
| S-EPMC4878291 | biostudies-literature
Project description:BackgroundHPV 16 is the cause of cervical carcinoma, but only a small fraction of women with HPV infection progress to this pathology. Besides persistent infection and HPV integration, several studies have suggested that HPV intratype variants may contribute to the development of cancer. The purpose of this study was to investigate the nucleotide variability and phylogenetically classify HPV 16 E6 variants circulating over a period of 16 years in women from Southern Mexico, and to analyze its association with precursor lesions and cervical carcinoma.MethodsThis study was conducted in 330 cervical DNA samples with HPV 16 from women who were residents of the State of Guerrero, located in Southern Mexico. According of cytological and/or histological diagnosis, samples were divided into the following four groups: no intraepithelial lesion (n = 97), low-grade squamous intraepithelial lesion (n = 123), high-grade squamous intraepithelial lesion (n = 19) and cervical carcinoma (n = 91). HPV 16 E6 gene was amplified, sequenced and aligned with reference sequence (HPV 16R) and a phylogenetic tree was constructed to identify and classify HPV 16 variants. Chi squared was used and data analysis and statistics were done with SPSS Statistics and STATA softwares.ResultsTwenty seven HPV 16 E6 variants were detected in women from Southern Mexico, 82.12% belonged to the EUR, 17.58% to AA1 and 0.3% to Afr2a sublineages. The most common was E-G350 (40%), followed by E-prototype (13.03%), E-C188/G350 (11.82%), AA-a (10.61%), AA-c (6.07%) and E-A176/G350 (5.15%). Eight new E6 variants were found and 2 of them lead to amino acid change: E-C183/G350 (I27T) and E-C306/G350 (K68T). The HPV 16 variant that showed the greatest risk of leading to the development of CC was AA-a (OR = 69.01, CI = 7.57-628.96), followed by E-A176/G350 (OR = 39.82, CI = 4.11-386.04), AA-c (OR = 21.16, CI 2.59-172.56), E-G350 (OR = 13.25, CI = 2.02-87.12) and E-C188/G350 (OR = 10.48, CI = 1.39-78.92).ConclusionsThe variants more frequently found in women with cervical carcinoma are E-G350, AA-a, AA-c, E-C188/G350 and E-A176/G350. All of them are associated with the development of cervical carcinoma, however, AA-a showed the highest association. This study reinforces the proposal that HPV 16 AA-a is an oncogenic risk for cervical carcinoma progression in Mexico.
| S-EPMC4351832 | 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.
| S-EPMC4461273 | biostudies-literature
Project description:The Carolina Women's Care Study (CWCS) at the University of South Carolina followed 467 young women with the goal of identifying biomarkers of human papillomavirus (HPV) persistence. In this study, we analyzed the methylation of HPV16 DNA.The aims of this study were to determine the methylation status of the HPV16 L2 gene in DNA isolated from exfoliated cervical cells collected longitudinally as part of the CWCS and to determine the prevalence of polymorphisms (single nucleotide polymorphisms [SNPs]) in folate metabolizing enzymes and DNA repair enzymes known to affect DNA methylation in blood-derived genomic DNA from CWCS participants. For methylation studies, DNA samples were bisulfite converted and amplified with the EpiTect Whole Bisulfitome kit. Polymerase chain reaction was performed for amplicons containing 5 CpG sites in L2. Pyrosequencing was carried out using EpigenDx and analyzed with PyroMark Software. Taqman genotyping assays were performed to determine selected SNP alleles in the CWCS cohort.Methylation data were obtained for 82 samples from 27 participants. Of these, 22 participants were positive for HPV16 for 3 or more visits (?12 months). Methylation in L2 was detectable, but methylation levels varied and were not associated with HPV16 persistence. No linearity of methylation levels over time was observed in participants for whom longitudinal data could be analyzed. Analysis of 9 selected SNPs did not reveal an association with persistence. We conclude that at early stages of infection methylation of HPV16 L2 DNA in Pap test samples is not a predictive biomarker of HPV persistence.
| S-EPMC5037005 | biostudies-literature
Project description:BackgroundThe purpose of this study was to examine the rate of and risks for cervical human papillomavirus type 16 (HPV16) redetection in women with documented or suspected HPV16 infection.MethodsA convenience sample of women aged 13-21 years were seen at 4-month intervals for HPV DNA testing and cytology. Serum samples were obtained at baseline and annually.ResultsA total of 1543 women entered the study. Of the 295 women with detection of HPV16 DNA and subsequent clearance, 18.1% had HPV16 redetected by 8.5 years (88% cleared this second detection by 3 years). Of the 247 women who had antibodies to HPV16 and were HPV16 DNA negative at baseline, 15.3% had HPV16 redetected by year 5. Risks for redetection included douching, current use of medroxyprogesterone, reporting >1 sex partner or having a new sex partner, and having a sexually transmitted infection. Development of cervical intraepithelial neoplasia 2/3 was rare in women with redetection, except for those with prevalent HPV16 infection.ConclusionsReappearance of HPV16 DNA was observed in 18% of women. Most are associated with sexual exposure and appear benign. Interpretation of the studies is more complex in women with prevalent infections as it appears that this small subset reflects women with persistence already present at entry.
| S-EPMC3699002 | biostudies-literature