Donà Maria Gabriella, Paolini Francesca, Benevolo Maria, Rollo Francesca, Merenda Elisabetta, Giuliani Eugenia, Campo Flaminia, Bonomo Claudia, Lorusso Francesco, Cecconi Fabio, Antonelli Rita, Mantia Ignazio La, D'Ermo Giuseppe, Covello Renato, Pichi Barbara, Pellini Raul, De Freitas Antonio Carlos, Sharabi Andrew, Venuti Aldo
STI/HIV Unit, San Gallicano Dermatological Institute IRCCS, Rome, Italy.
HPV-Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
BMC Cancer. 2025 Aug 7;25(1):1274. doi: 10.1186/s12885-025-14506-0.
HPV16 is implicated in around 30% of oropharyngeal cancers (OPCs). HPV-associated OPCs generally show a better prognosis, but 20% deviate from this trend, indicating a need for better molecular profiling. HPV16-E5 is an oncoprotein encoded by an mRNA that undergoes extensive splicing, with only one specific transcript being translatable. The prognostic significance of this E5-productive transcript in HPV-related OPCs is not well-studied.
We retrospectively analysed 74 HPV16-positive OPC cases diagnosed between 2011 and 2021. FFPE tissue samples were used for p16, EGFR, and HLA-I analysis by immunohistochemistry while E5, productive E5, E6 and E7 transcripts were detected by qPCR. Survival analysis was conducted using Kaplan-Meier curves and log-rank tests.
Productive HPV16-E5 transcripts were detected in 11.3% of OPCs. There was no significant association between HPV16-E5 transcripts and EGFR or HLA-I expression. However, the presence of the productive E5 transcript was associated with worse progression-free survival (PFS) (p = 0.0024). EGFR or HLA-I expression was not significantly associated with PFS (p = 0.17 and p = 0.93, respectively).
This study demonstrates for the first time the presence of E5-productive transcripts in HPV16-positive OPCs and its association with poorer PFS, highlighting its potential as a prognostic marker. Further research with larger cohorts is needed to validate these findings.
约30%的口咽癌（OPC）与HPV16有关。HPV相关的OPC通常预后较好，但20%的病例偏离了这一趋势，这表明需要更好的分子特征分析。HPV16-E5是一种由经过广泛剪接的mRNA编码的癌蛋白，只有一种特定的转录本可被翻译。这种产生E5的转录本在HPV相关OPC中的预后意义尚未得到充分研究。
我们回顾性分析了2011年至2021年间诊断的74例HPV16阳性OPC病例。通过免疫组织化学对福尔马林固定石蜡包埋（FFPE）组织样本进行p16、表皮生长因子受体（EGFR）和人类白细胞抗原I（HLA-I）分析，同时通过定量聚合酶链反应（qPCR）检测E5、产生E5的转录本、E6和E7转录本。使用Kaplan-Meier曲线和对数秩检验进行生存分析。
在11.3%的OPC中检测到产生HPV16-E5的转录本。HPV16-E5转录本与EGFR或HLA-I表达之间无显著关联。然而，产生E5的转录本的存在与无进展生存期（PFS）较差相关（p = 0.0024）。EGFR或HLA-I表达与PFS无显著关联（分别为p = 0.17和p = 0.93）。
本研究首次证明了HPV16阳性OPC中存在产生E5的转录本及其与较差PFS的关联，突出了其作为预后标志物的潜力。需要对更大的队列进行进一步研究以验证这些发现。
