Whole Genome Sequencing and Evolutionary Analysis of Human Papillomavirus Type 16 in Central China

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
PLoS ONE (Impact Factor: 3.53). 05/2012; 7(5):e36577. DOI: 10.1371/journal.pone.0036577
Source: PubMed

ABSTRACT Human papillomavirus type 16 plays a critical role in the neoplastic transformation of cervical cancers. Molecular variants of HPV16 existing in different ethnic groups have shown substantial phenotypic differences in pathogenicity, immunogenicity and tumorigenicity. In this study, we sequenced the entire HPV16 genome of 76 isolates originated from Anyang, central China. Phylogenetic analysis of these sequences identified two major variants of HPV16 in the Anyang area, namely the European prototype (E(p)) and the European Asian type (E(As)). These two variants show a high degree of divergence between groups, and the E(p) comprised higher genetic diversity than the E(As). Analysis with two measurements of genetic diversity indicated that viral population size was relatively stable in this area in the past. Codon based likelihood models revealed strong statistical support for adaptive evolution acting on the E6 gene. Bayesian analysis identified several important amino acid positions that may be driving adaptive selection in the HPV 16 population, including R10G, D25E, L83V, and E113D in the E6 gene. We hypothesize that the positive selection at these codons might be a contributing factor responsible for the phenotypic differences in carcinogenesis and immunogenicity among cervical cancers in China based on the potential roles of these molecular variants reported in other studies.

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    ABSTRACT: Human papillomavirus (HPV) has several intragenotypic variants with different geographical and ethnic distributions. This study aimed to elucidate the distribution patterns of E6 and E7 (E6/E7) intragenotypic variants of HPV type 16 (HPV-16), which is most common worldwide, and HPV-52, which is common in Asian countries such as Japan, the Philippines, and Vietnam. In previous studies, genomic DNA samples extracted from cervical swabs were collected from female sex workers in these three countries and found to be positive for HPV-16 or HPV-52. Samples were amplified further for their E6/E7 genes using type-specific primers and analyzed genetically. Seventy-nine HPV-16 E6/E7 genes were analyzed successfully and grouped into three lineages: European (Prototype), European (Asian), and African-2. The prevalences of HPV-16 European (Prototype)/European (Asian) lineages were 19.4%/80.6% (n = 31) in Japan, 75.0%/20.8% (n = 24) in the Philippines, and 0%/95.8% (n = 24) in Vietnam. The 109 HPV-52 E6/E7 genes analyzed successfully were grouped into four lineages, A-D; the prevalences of lineages A/B/C/D were, respectively, 5.1%/92.3%/0%/2.6% in Japan (n = 39), 34.4%/62.5%/0%/3.1% in the Philippines (n = 32), and 15.8%/73.7%/7.9%/2.6% in Vietnam (n = 38). The distribution patterns of HPV-16 and HPV-52 lineages in these countries differed significantly (P < 0.000001 and P = 0.0048, respectively). There was no significant relationship between abnormal cervical cytology and either HPV-16 E6/E7 lineages or specific amino acid mutations, such as E6 D25E, E6 L83V, and E7 N29S. Analysis of HPV-16 and HPV-52 E6/E7 genes can be a useful molecular-epidemiological tool to distinguish geographical diffusion routes of these HPV types in Asia. J. Med. Virol. 85: 1069-1076, 2013. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 06/2013; 85(6):1069-76. DOI:10.1002/jmv.23566 · 2.22 Impact Factor
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    ABSTRACT: Worldwide, cervical cancer is the second most common cancer in women. High-risk human papillomavirus (HPV) play a crucial role in the etiology of cervical cancer and the most prevalent genotype is HPV16. HPV 16 intratypic variants have been reported to differ in their prevalence, biological and biochemical properties. The present study was designed to analyze and identify HPV type 16 E6 variants among patients with cervical cancer in Morocco. A total of 103 HPV16 positive samples were isolated from 129 cervical cancer cases, and variant status was subsequently determined by DNA sequencing of the E6 gene. Isolates from patients were grouped into the European (E), African (Af) and North-American (NA1) phylogenetic clusters with a high prevalence of E lineage (58.3%). The Af and NA1 variants were detected in 31.1% and 11.6% of the HPV16 positive specimens, respectively, whereas, only 3% of cases were prototype E350T. No European-Asian (EA), Asian (As) or Asian-American (AA) variants were observed in our HPV16-positive specimens. At the amino acid level, the most prevalent non-synonymous variants were L83V (T350G), H78Y (C335T), E113D (A442C), Q14D (C143G/G145T) and R10I (G132T), and were observed respectively in 65%, 41.8%, 38.8%, 30.1% and 23.3% of total samples.Moreover, HPV16 European variants were mostly identified in younger women at early clinical diagnosis stages. Whereas, HPV16 Af variants were most likely associated with cervical cancer development in older women with pronounced aggressiveness. This study suggests a predominance of E lineage strains among Moroccan HPV 16 isolates and raises the possibility that HPV16 variants have a preferential role in progression to malignancy and could be associated with the more aggressive nature of cervical cancer.
    BMC Infectious Diseases 08/2013; 13(1):378. DOI:10.1186/1471-2334-13-378 · 2.56 Impact Factor

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