ArticleDiscover oncology2026
Identification of a 32-gene signature that determines HPV status in head and neck cancer.
Article in Discover oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundDetermination of HPV status for head and neck cancer (HNSCC) is prognostically important, and various testing modalities are commonly used. Discordant results are occasionally observed. We aimed to evaluate accuracy of multiple HPV testing modalities, develop a new, highly accurate HPV signature that we hypothesize will capture HPV-related oncogenic processes, and make recommendations for HPV testing in an era where HPV informs treatment decisions.
methodsHNSCC samples from the Chicago HNSCC Genomics Cohort (CHGC) were evaluated by: (1) E6 PCR (DNA), (2) qPCR for E6, E7 (HPV16), E6, L1 (HPV18) (mRNA), (3) p16 expression by IHC and, (4) CDKN2A expression (mRNA), and (5) TP53 mutational status. In addition, HPV DNA and RNA were determined for TCGA samples using exome and RNA-seq data, respectively. A gene expression (GE) signature for predicting HPV status was developed based on CHGC and TCGA cohorts and validated by two independent datasets.
resultsDNA and RNA based (PCR) approaches appeared to be similarly accurate and concordant in 97% of samples. p16 IHC/mRNA misclassified 12.2% cases in oropharynx tumors (87.8% accurate), and in non-oropharynx tumors was not useful due to high rates of false-positive results. The newly developed HPV-GE signature allowed to reconcile discrepant cases, was similarly accurate as PCR, but also missed cases. HPV-GE allowed annotation with biologic processes and identified tumors with overlapping biology between HPV + and - tumors. TP53 mutation status performed poorly as an HPV surrogate.
conclusionsIn summary, no single test was perfectly accurate. Both PCR-based methods and the HPV-GE signature aligned well with consensus status and, unlike p16 IHC, are applicable across all head and neck tumor sites. The HPV-GE signature further supports the concept of biological overlap between HPV(+) and HPV(-) HNSCC in some cases. For research and retrospective stratification, a dual-modality approach (e.g., p16 IHC plus PCR or HPV-GE) offers a more robust assessment than any single test.
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