Li Qiongyao, Cheng Qichen, Tian Di, An Zhengyuan, Li Lei, Yang Feng, Zhang Mingjing, Liu Ganglin, Peixin A, Yang Yan, Chen Zuyi
Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, China.
Information Division, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
Virol J. 2025 Apr 26;22(1):121. doi: 10.1186/s12985-025-02752-4.
There is a lack of research on the relations among genetic polymorphisms, viral load, adaptability, persistent infection ability, and pathogenicity of human papillomavirus (HPV) type 33. Understanding these relations is crucial for revealing its pathogenic mechanisms and formulating prevention strategies.
Exfoliated cervical cells were harvested from female participants in three hospitals located in the southwestern region of China (Guizhou, Sichuan, and Chongqing). Real-time fluorescence PCR technology was used for HPV genotyping and genomic quantification, and Sanger sequencing was used to obtain the gene sequence. then, changing trends in HPV33 detection rates and E6/E7 allele frequencies were compared. Positive selection, viral load, pathogenicity, and persistent infection capacity of different E6/E7 variants/mutations were analyzed.
Among 239,743 samples, HPV detection number was 56,681, the HPV33 detection rate was 3.72% (2,110/56,681) among all detected HPV genotypes. Between 2009 and 2023, a downward trend in the HPV33 detection rate was observed. The E6 + E7 prototype (E6 + E7 on the same variant is consistent with the reference sequence) was the dominant variant, with a significantly increased allele frequency. This dominant variant showed a significantly higher relative risk in causing persistent infection and cervical diseases (cervical intraepithelial neoplasia and cervical cancer). The viral load in the cervical disease group was significantly higher than that in the lesion-free group, and the viral load in the persistent infection group was significantly higher than that in the viral clearance group. There was no correlation between viral load and major genetic variants/mutations.
The E6 + E7 prototype has a significant impact on the pathogenicity and persistent infection capacity of HPV33. Viral load is positively correlated with pathogenicity and persistent infection capacity. It may serve as a biomarker for predicting disease progression during HPV33 screening. Other mechanisms underlying allele replacement require further investigation.
关于人乳头瘤病毒33型（HPV33）的基因多态性、病毒载量、适应性、持续感染能力和致病性之间的关系，目前缺乏相关研究。了解这些关系对于揭示其致病机制和制定预防策略至关重要。
从中国西南地区（贵州、四川和重庆）的三家医院的女性参与者中采集宫颈脱落细胞。采用实时荧光PCR技术进行HPV基因分型和基因组定量，并使用桑格测序法获取基因序列。然后，比较HPV33检测率和E6/E7等位基因频率的变化趋势。分析不同E6/E7变体/突变的正选择、病毒载量、致病性和持续感染能力。
在239,743份样本中，HPV检测阳性数为56,681份，在所有检测到的HPV基因型中，HPV33的检测率为3.72%（2,110/56,681）。2009年至2023年期间，观察到HPV33检测率呈下降趋势。E6 + E7原型（同一变体上的E6 + E7与参考序列一致）是主要变体，等位基因频率显著增加。这种主要变体在导致持续感染和宫颈疾病（宫颈上皮内瘤变和宫颈癌）方面显示出显著更高的相对风险。宫颈疾病组的病毒载量显著高于无病变组，持续感染组的病毒载量显著高于病毒清除组。病毒载量与主要基因变体/突变之间无相关性。
E6 + E7原型对HPV33的致病性和持续感染能力有显著影响。病毒载量与致病性和持续感染能力呈正相关。它可作为HPV33筛查期间预测疾病进展的生物标志物。等位基因替换的其他潜在机制需要进一步研究。
