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.
Highlights
IntroductionInfection with high risk types of Human papillomaviruses (HPVs) is a necessary factor for the development of precancerous lesions and cervical cancer [2,3,4]
Human papillomaviruses (HPVs) are common and are clinically important pathogens [1]
HPV infection and PCR amplification With the carefully designed PCR primers, we were able to detect HPV in 87 (92.5%) of the 94 cancer samples. Of these 87 samples, 80 cases were positive for HPV16
Summary
Infection with high risk types of HPV is a necessary factor for the development of precancerous lesions and cervical cancer [2,3,4] Of those that can infect human beings, over 120 different types have been isolated, and among these around 20 types are classified as high-risk HPV types (HR-HPV) based on their established association with cancer [1,5,6]. Through epidemiological and in-vitro experimental studies, natural variants of HPV16 have shown substantial differences in pathogenicity, immunogenicity and tumorigenicity. These variants may reflect the evolution of the viral population as it has adapted to local human ethnic groups [13]. By studying molecular evolution of the viral genomes, patterns of this evolutionary history can be identified and important molecular variants responsible for viral pathogenicity and carcinogenesis may be characterized [14]
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