HPV16早期转录物的表达水平与宫颈病变的自然史无关。
The level of expression of HPV16 early transcripts is not associated with the natural history of cervical lesions.
发表日期:2024 Sep
作者:
Elise Jacquin, Maëlle Saunier, Quentin Lepiller, Franck Monnien, Frédéric Mauny, Rajeev Ramanah, Xavier Carcopino, Didier Riethmuller, Christiane Mougin, Jean-Luc Prétet
来源:
JOURNAL OF MEDICAL VIROLOGY
摘要:
宫颈癌的自然史与高危人乳头瘤病毒(HPV)感染密切相关。人们认识到,在 HPV DNA 整合后,E2 开放阅读框的部分或完全丢失会阻止相应蛋白质的表达,导致 E6 和 E7 病毒癌蛋白上调。为了更好地表征宫颈水平的 HPV16 感染,对代表全谱宫颈疾病的 158 个宫颈标本的病毒载量、病毒 DNA 整合和病毒早期转录表达(E2、E5 和 E6)进行了分析。总体而言,早期转录本检测的频率从 45% 到 90% 不等,并且随着病变严重程度而增加。此外,高级病变中E2、E5和E6转录物表达水平略高于无异常宫颈标本。值得注意的是,早期转录本表达与病毒载量明显相关,并且 E2 和 E6 转录本表达之间没有发现负相关。早期转录物表达与 HPV16 DNA 整合之间没有发现明显的关联,但具有完全整合的 HPV16 基因组的样本不包含 E2 或 E5 转录物。总之,早期 HPV16 转录物表达似乎与病毒载量相关,而不是与病变级别相关。从实际角度来看,HPV16 早期转录本的量化很难转化为宫颈癌筛查的相关生物标志物。© 2024 Wiley periodicals LLC。
The natural history of cervical cancer is closely linked to that of high-risk human papillomaviruses (HPV) infection. It is recognized that upon HPV DNA integration, partial or complete loss of the E2 open reading frame precludes expression of the corresponding protein, resulting in upregulation of the E6 and E7 viral oncoproteins. To better characterize HPV16 infection at the cervical level, viral load, viral DNA integration, and viral early transcript expression (E2, E5, and E6) were analyzed in a series of 158 cervical specimens representative of the full spectrum of cervical disease. Overall, the frequency of early transcript detection varied from 45% to 90% and tended to increase with lesion severity. In addition, the levels of E2, E5, and E6 transcript expression were slightly higher in high-grade lesions than in cervical specimens without abnormalities. Notably, early transcript expression was clearly associated with viral load, and no inverse correlation was found between the expression of E2 and E6 transcripts. No clear association was found between early transcript expression and HPV16 DNA integration, with the exception that samples with a fully integrated HPV16 genome did not harbor E2 or E5 transcripts. In conclusion, early HPV16 transcript expression appears to be associated with viral load rather than lesion grade. From a practical point of view, quantification of HPV16 early transcripts is difficult to translate into a relevant biomarker for cervical cancer screening.© 2024 Wiley Periodicals LLC.