Cervical carcinogenesis risk association of HPV33 E6 and E7 genetic variations in Taizhou, Southeast China

traits of the population under study

A total of 189 women with one HPV33 infection were chosen between February 2014 and December 2020. The range of 19 to 73 years was 42.3 years old on average. The entire E6 and E7 gene family from HPV33 was successfully sequenced in 185 ( 97.9 %) sequences. The remaining 4 ( 2.1 %%) sequences were excluded because there weren’t many HPV copies available. 110 ( 59.5 %) of the 185 cases underwent colposcopy biopsy for histological diagnosis, including 57 who had healthy cervices after the procedure, 17 of whom had CIN1, 16 of which had CINIC2, and 20 did not have cervical cancer. Table & nbsp, 1. displays the characteristics of the study population.

Table 1 traits of the population under study categorized by HPV33 (sub)lineage

variations in the genes E6 and E7

59 of the <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02125-9#Fig1“>185 HPV33 samples( 3<a data-track="click" data-track-label="link" data-track-action="figure anchor" href="https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02125-9#Fig1“>1.9 %) displayed nucleotide variations when compared to M<a data-track="click" data-track-label="link" data-track-action="figure anchor" href="https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02125-9#Fig1“>12732.<a data-track="click" data-track-label="link" data-track-action="figure anchor" href="https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02125-9#Fig1“>1. All variations in nucleotide and amino acid sequences in the entire E6 and E7 fragments of the HPV33 lineage / sublineages are visually distinguished by Figure & nbsp. In this study, the HPV33 E6 / E7 variants, which were published with GenBank accession nos. 33CNTZ0<a data-track="click" data-track-label="link" data-track-action="figure anchor" href="https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02125-9#Fig1“>1 – 33BNTZ<a data-track="click" data-track-label="link" data-track-action="figure anchor" href="https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02125-9#Fig1“>15, were found to have <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02125-9#Fig1“>15 different variation patterns. The most prevalent variant in the Taizhou-based population, with complete E6 and E7 sequence homology with M<a data-track="click" data-track-label="link" data-track-action="figure anchor" href="https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02125-9#Fig1“>12732.<a data-track="click" data-track-label="link" data-track-action="figure anchor" href="https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02125-9#Fig1“>1, was OQ672665 to Oq672779.33CNTZ0<a data-track="click" data-track-label="link" data-track-action="figure anchor" href="https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02125-9#Fig1“>1( 68.<a data-track="click" data-track-label="link" data-track-action="figure anchor" href="https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02125-9#Fig1“>1 %, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02125-9#Fig1“>126 / <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02125-9#Fig1“>185 ). The novel HPV33 E6 / E7 variants, which are highlighted in bold in Fig., included ten( 66.7 %, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02125-9#Fig1“>10 / <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02125-9#Fig1“>15 ). & nbsp, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02125-9#Fig1“>1.

Fig. 1.
figure 1
Genetic variation in the Southeast Chinese Taizhou region’s HPV33 E6 and E7 nucleotide sequences. The first nucleotide of the HPV33 prototype reference sequence( GenBank: M12732.1 ) is referred to as the number. Each row indicates the variant identification and the nucleotide sequence alignment compared to the reference. Novel HPV33 variants are highlighted in bold and novel nucleotide substitutions are highlights in gray

Altogether, 20 single nucleotide substitutions were identified, with 6 ( 30.0 %) novel substitutions and 10 ( 50.0 %) nonsynonymous substitutions. Nonsynonymous substitutions included T196G( C30G ), A213C ( K35N ), C245T ( A46V ), A364C ( N86H ), A387C ( K93N ), A446G ( Q113R ), and G458T ( R117L ) in the E6 sequence and C706T( A45V ), C706A ( A45E ), and A862T( Q97L ) in the E7 sequence. To our knowledge, the nucleotide substitutions of T196G ( C30G ), A447T, G458T ( R117L ), G531A, A704A, and C740T have not been reported in previous studies.

Phylogenetic construction

The phylogenetic tree was constructed from 21 complete HPV33 E6 and E7 sequences( 15 obtained from our study and 6 from GenBank )( Fig. & nbsp, 2 ). Based on the phylogenetic tree, sublineages A1, A2, and A3 were detected in 75.7 %( 140 / 185 ), 1.1 %( 2 / 185 ), and 23.2 %( 43 / 185 ) of samples, respectively. All HPV33 E6 / E7 variants belonged to lineage A, whereas no variants belonged to lineage B or lineage C in the present study.

Fig. 2
figure 2
Phylogenetic tree of the HPV33 E6 / E7 variants. Maximum – likelihood analysis( with MEGA X ) of E6 and E7 nucleotide sequences was inferred from 15 obtained HPV33 E6 / E7 variants and 5 reference sequences. Numbers below branches indicate bootstrap values

Risk association with cervical lesions

Our data suggested that the proportion of sublineage A1 in CIN2 / 3 was higher when compared with CIN1, but it was not significant( 76.5 % vs. 80.6 %, P & gt, 0.05 ). There was no significant difference in the risk of cervical lesions between sublineage A1 and other HPV33 E6 / E7 variants. No significant difference was observed in the relative risk for cervical lesions among the nucleotide variations in the HPV33 E6 and E7 genes( Table & nbsp, 1 ).

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Categorized as Virology

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