Dataset Information

HPV-16, HPV-58, and HPV-33 are the most carcinogenic HPV genotypes in Southwestern China and their viral loads are associated with severity of premalignant lesions in the cervix.

ABSTRACT: BACKGROUNDCurrently, the role of human papillomavirus (HPV)-58 in southwestern China has been unexplored. Although there is some controversy, it is proposed that the viral load of HPV correlates with the severity of intraepithelial lesions.METHODSWe identified 7747 patients from south Sichuan and adjacent regions who were diagnosed with HPV between 2013 and 2017. The HR-HPV subtype distribution was analyzed and the patient's viral loads were quantified using real-time RT-PCR.RESULTSAmong all 7747 patients screened for HPV genotypes, 1728 patients (22.31%) were identified as having HR-HPV subtypes. In patients without intraepithelial lesions (12.41%), HPV-52, HPV-16, and HPV-58 were the three most prevalent HR-HPV subtypes. Moreover, HPV-16, HPV-58, and HPV-33 were the most prevalent subtypes in patients with cervical intraepithelial neoplasia grade II (CINII) (42.86%) and grade III (CINIII) (59.81%), and accounted for the majority of invasive cervical cancer (ICC) (69.34%). Thus, viral loads of HPV-58, HPV-16, and HPV-33 positively correlated with the severity of cervical lesions (P?CONCLUSIONIn our study, we showed that HPV-16 was the most common carcinogenic HPV subtype in southwestern China followed by HPV-58 and HPV-33. Viral loads of these subtypes are associated with the severity of premalignant lesions in the cervix.

SUBMITTER: Long W

PROVIDER: S-EPMC5970451 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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HPV-16, HPV-58, and HPV-33 are the most carcinogenic HPV genotypes in Southwestern China and their viral loads are associated with severity of premalignant lesions in the cervix.

Long Wenbo W Yang Zixi Z Li Xiabin X Chen Ming M Liu Jie J Zhang Yuanxue Y Sun Xingwang X

Virology journal 20180525 1

<h4>Background</h4>Currently, the role of human papillomavirus (HPV)-58 in southwestern China has been unexplored. Although there is some controversy, it is proposed that the viral load of HPV correlates with the severity of intraepithelial lesions.<h4>Methods</h4>We identified 7747 patients from south Sichuan and adjacent regions who were diagnosed with HPV between 2013 and 2017. The HR-HPV subtype distribution was analyzed and the patient's viral loads were quantified using real-time RT-PCR.<h ...[more]

PMID: 29801461

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Project description:BackgroundHuman papillomavirus (HPV) E6 and E7 oncoproteins play a crucial role in HPV-related diseases, such as cervical cancer, and can be used as ideal targets for therapeutic vaccines. Human leukocyte antigen (HLA) participates in the immune response to block HPV infection and invasion by its target/recognition function. HPV-33 and HPV-58 are highly prevalent among Chinese women. Therefore, it is of great significance to study the E6 and E7 region-specific gene polymorphisms of HPV-33 and HPV-58 in Southwest China and to identify ideal epitopes for vaccine design. Both HPV-33 and HPV-58 belong to α-9 genus HPV and are highly homologous, so their correlations are included in our research.MethodsTo study the E6 and E7 variations and polymorphisms of HPV-33 and HPV-58 in Southwest China, we collected samples, extracted and sequenced DNA, and identified variants. Nucleotide sequences were translated into amino acids by Mega 6.0 software. The physical/chemical properties, amino acid-conserved sequences and secondary structure of protein sequences were analysed by the Protparam server, ConSurf server and PSIPRED software. The T and B cell epitopes of the E6/E7 reference and variant sequences in HPV-33 and HPV-58 were predicted by the Immune Epitope Database (IEDB) analysis server and the ABCpred server, respectively.ResultsFive and seven optimal HLA-I restricted T cell epitopes were selected from HPV-33 and HPV-58 E6, respectively, and these optimal epitopes are mainly located in 41-58EVYDFAFADLTVVYREGN of HPV-33 E6 and 40-60SEVYDFVFADLRIVYRDGNPF of HPV-58 E6. Six optimal HLA-I-restricted T cell epitopes were selected from HPV-33 and HPV-58 E7, and these epitopes are mainly located in 77-90RTIQQLLMGTVNIV of HPV-33 E7 and 78-91RTLQQLLMGTCTIV of HPV-58 E7.ConclusionsHPV-33/HPV-58 E6/E7 gene polymorphisms and T/B cell epitopes of their reference and variant sequences were studied, and candidate epitopes were selected by bioinformatics techniques for therapeutic vaccine design for people in Southwest China. This study was the first to investigate the correlation of epitopes between HPV-33 and HPV-58. After experimental validation, these selected epitopes will be employed to induce a wide range of immune responses in heterogeneous HLA populations.

Project description:HPV account for most of the incidence of cervical cancer. Approximately 90% of anal cancers and a smaller subset (<50%) of other cancers (oropharyngeal, penile, vaginal, vulvar) are also attributed to HPV. The L1 protein comprising HPV vaccine formulations elicits high-titre neutralizing antibodies and confers type restricted protection. The L2 protein is a promising candidate for a broadly protective HPV vaccine. In our previous study, we found the most prevalent high-risk HPV infectious serotypes were HPV-16 and HPV-58 among women of Southwest China. To explore gene polymorphisms and intratypic variations of HPV-16 and HPV-58 L1/L2 genes originating in Southwest China, HPV-16 (L1: n = 31, L2: n = 28) and HPV-58 (L1: n = 21, L2: n = 21) L1/L2 genes were sequenced and compared to others described and submitted to GenBank. Phylogenetic trees were then constructed by Neighbor-Joining and the Kimura 2-parameters methods (MEGA software), followed by an analysis of the diversity of secondary structure. Then selection pressures acting on the L1/L2 genes were estimated by PAML software. Twenty-nine single nucleotide changes were observed in HPV-16 L1 sequences with 16/29 non-synonymous mutations and 13/29 synonymous mutations (six in alpha helix and two in beta turns). Seventeen single nucleotide changes were observed in HPV-16 L2 sequences with 8/17 non-synonymous mutations (one in beta turn) and 9/17 synonymous mutations. Twenty-four single nucleotide changes were observed in HPV-58 L1 sequences with 10/24 non-synonymous mutations and 14/24 synonymous mutations (eight in alpha helix and four in beta turn). Seven single nucleotide changes were observed in HPV-58 L2 sequences with 4/7 non-synonymous mutations and 3/7 synonymous mutations. The result of selective pressure analysis showed that most of these mutations were of positive selection. This study may help understand the intrinsic geographical relatedness and biological differences of HPV-16/HPV-58 and contributes further to research on their infectivity, pathogenicity, and vaccine strategy.

Project description:BackgroundPersistent human papillomavirus (HPV) infection is a key factor for the development and progression of cervical cancer. We sought to identify the type-specific HPV prevalence by cervical cytology and assess disease progression risk based on high-risk persistent HPV infection in South Korea.MethodsTo investigate the HPV prevalence by Pap results, we searched seven literature databases without any language or date restrictions until July 17, 2019. To estimate the risk of disease progression by HPV type, we used the Korea HPV Cohort study data. The search included the terms "HPV" and "Genotype" and "Korea." Studies on Korean women, type-specific HPV distribution by cytological findings, and detailed methodological description of the detection assay were included. We assessed the risk of disease progression according to the high-risk HPV type related to the nonavalent vaccine and associated persistent infections in 686 HPV-positive women with atypical squamous cells of uncertain significance or low-grade squamous intraepithelial lesions from the Korea HPV Cohort Study. Type-specific HPV prevalence was the proportion of women positive for a specific HPV genotype among all HPV-positive women tested for that genotype in the systematic review.ResultsWe included 23 studies in our review. HPV-16 was the most prevalent, followed by HPV-58, -53, -70, -18, and -68. In women with high-grade squamous intraepithelial lesions, including cancer, HPV-16, -18, and -58 were the most prevalent. In the longitudinal cohort study, the adjusted hazard ratio of disease progression from atypical squamous cells of uncertain significance to high-grade squamous intraepithelial lesions was significantly higher among those with persistent HPV-58 (increase in risk: 3.54-5.84) and HPV-16 (2.64-5.04) infections.ConclusionsWhile HPV-16 was the most prevalent, persistent infections of HPV-16/58 increased the risk of disease progression to high-grade squamous intraepithelial lesions. Therefore, persistent infections of HPV-16 and -58 are critical risk factors for cervical disease progression in Korea. Our results suggest that equal attention should be paid to HPV-58 and -16 infections and provide important evidence to assist in planning the National Immunization Program in Korea.

Dataset Information

HPV-16, HPV-58, and HPV-33 are the most carcinogenic HPV genotypes in Southwestern China and their viral loads are associated with severity of premalignant lesions in the cervix.

Publications

HPV-16, HPV-58, and HPV-33 are the most carcinogenic HPV genotypes in Southwestern China and their viral loads are associated with severity of premalignant lesions in the cervix.

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