ArticleCancers2022
Concordance of p16
Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.
- Diagnostic Accuracy of p16 Immunohistochemistry as a Marker of High-Risk HPV in Invasive Laryngeal Squamous Cell Carcinoma: A Systematic Review.Medicina (Kaunas, Lithuania) · 2026Pooled it
- A systematic literature review of the human papillomavirus prevalence in locally and regionally advanced and recurrent/metastatic head and neck cancers through the last decade: The "ALARM" study.Cancer medicine · 2024Pooled it
- HPV Detection in Oropharyngeal Cancer: A Narrative Review of Diagnostic and Emerging Molecular Approaches.Diagnostics (Basel, Switzerland) · 2026Review
- Advancements in Image-Based Artificial Intelligence in the Diagnosis and Treatment of Head and Neck Squamous Cell Carcinoma: A Narrative Review.International journal of general medicine · 2026Review
- Human papillomavirus 16 E6 oncoprotein promotes up-regulation of RNA-binding protein Sam68 in head and neck cancer.Frontiers in microbiology · 2026Article
- The impact of histopathology on prognosis of squamous cell carcinoma of the larynx: can we do better?Virchows Archiv : an international journal of pathology · 2025Review
- HPV Biomarkers in Oral and Blood-Derived Body Fluids in Head and Neck Cancer Patients.Journal of medical virology · 2025Article
- Human papillomavirus-driven head and neck cancers in Japan during 2008-2009 and 2018-2019: The BROADEN study.Cancer science · 2024Article
- Expression of EGFR and p16 in Squamous Cell Carcinoma of External Auditory Canal.The Kobe journal of medical sciences · 2024Article
- p16 Expression in Laryngeal Squamous Cell Carcinoma: A Surrogate or Independent Prognostic Marker?Pathogens (Basel, Switzerland) · 2024Review
- Ex Vivo Functional Assay for Evaluating Treatment Response in Tumor Tissue of Head and Neck Squamous Cell Carcinoma.Cancers · 2023Article
Corrections and comments
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Authors and funding
21 authors at 11 institutions in 6 countries.
Funding
Abstract
Background: Tests or test algorithms for diagnosing HPV-driven oral cavity and laryngeal head and neck carcinomas (HNC) have not been yet validated, and the differences among oral cavity and laryngeal sites have not been comprehensively evaluated. We aimed to assess the utility of a diagnostic algorithm for the detection of HPV-driven oral cavity (OCC), oropharyngeal (OPC) and laryngeal (LC) carcinomas using HPV-DNA testing followed by p16INK4a immunohistochemistry, taking E6*I mRNA detection as the reference standard. Methods: Formalin-fixed paraffin-embedded OCC, OPC, and LC carcinomas were collected from pathology archives in 29 countries. All samples were subjected to histopathological evaluation, DNA quality control, and HPV-DNA detection. All HPV-DNA-positive samples (including 78 OCC, 257 OPC, and 51 LC out of 3680 HNC with valid HPV-DNA results) were also tested for p16INK4a immunohistochemistry and E6*I mRNA. Three different cutoffs of nuclear and cytoplasmic staining were evaluated for p16INK4a: (a) >25%, (b) >50%, and (c) ≥70%. The concordance of p16INK4a and E6*I mRNA among HPV-DNA-positive OCC, OPC, and LC cases was assessed. Results: A total of 78 OCC, 257 OPC, and 51 LC were HPV-DNA-positive and further tested for p16INK4a and E6*I mRNA. The percentage of concordance between p16INK4a (cutoff ≥ 70%) and E6*I mRNA among HPV-DNA-positive OCC, OPC, and LC cases was 79.5% (95% CI 69.9−89.1%), 82.1% (95% CI 77.2−87.0%), and 56.9% (95% CI 42.3−71.4%), respectively. A p16INK4a cutoff of >50% improved the concordance although the improvement was not statistically significant. For most anatomical locations and p16INK4a cutoffs, the percentage of discordant cases was higher for HPV16- than HPV-non16-positive cases. Conclusions: The diagnostic algorithm of HPV-DNA testing followed by p16INK4a immunohistochemistry might be helpful in the diagnosis of HPV-driven OCC and OPC, but not LC. A different p16INK4a expression pattern was observed in those cases HPV-DNA-positive for types other than HPV16, as compared to HPV16-positive cases. Our study provides new insights into the use HPV-DNA, p16INK4a, and HPV-E6*I mRNA for diagnosing an HPV-driven HNC, including the optimal HPV test or p16INK4a cutoffs to be used. More studies are warranted to clarify the role of p16INK4a and HPV status in both OPC and non-OPC HNC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.