Detection and significance of HPV16 E5-specific productive transcripts in oropharyngeal carcinoma

Detection and significance of HPV16 E5-specific productive transcripts in oropharyngeal carcinoma

Abstract Background 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 spli...

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Main Authors: Maria Gabriella Donà, Francesca Paolini, Maria Benevolo, Francesca Rollo, Elisabetta Merenda, Eugenia Giuliani, Flaminia Campo, Claudia Bonomo, Francesco Lorusso, Fabio Cecconi, Rita Antonelli, Ignazio La Mantia, Giuseppe D’Ermo, Renato Covello, Barbara Pichi, Raul Pellini, Antonio Carlos De Freitas, Andrew Sharabi, Aldo Venuti
Format: Article
Language:English
Published: BMC 2025-08-01
Series:BMC Cancer
Subjects:
Oropharyngeal cancer (OPC)
HPV
E5 mRNA
Transcripts
HLA-I
EGFR
Online Access:https://doi.org/10.1186/s12885-025-14506-0
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Summary:Abstract Background 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. Methods 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. Results 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). Conclusions 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.
ISSN:1471-2407

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