Discordant Biomarkers Foretell Prognosis in Oropharyngeal Cancer
Mismatch between the p16 protein and human papillomavirus (HPV) biomarkers can abet settle prognosis in patients with oropharyngeal most cancers, European researchers reported.
Namely, oropharyngeal most cancers patients with discordance between the p16 (p16INK4a ) and HPV biomarker had vastly worse illness-free survival (DFS) and total survival (OS) than double-sure patients, though vastly better survival than double-damaging patients, in step with Hisham Mehanna, MBChB, PhD, of the Institute of Cancer and Genomics Sciences on the University of Birmingham in England, and colleagues, writing in Lancet Oncology.
5-yr DFS and OS charges of their multinational, individual affected person recordsdata prognosis involving nearly 8,000 patients were as follows:
- Double-sure (p16+/HPV+): 84.3% and 81.1%, respectively
- Discordant (p16-/HPV+): 71.1% and 53.2%
- Discordant (p16+/HPV-): 67.9% and 54.7%
- Double-damaging (p16-/HPV-): 60.8% and 40.4%
“Our findings indicate that classification of patients with oropharyngeal most cancers in step with p16-sure immunohistochemistry on my own is insufficient in a trial atmosphere, and is inclined to be insufficient in routine clinical be conscious, each for predicting prognosis and when deciding on treatment,” the authors wrote.
They explained that the incidence of oropharyngeal most cancers globally has been on the upward thrust since 2000, mostly attributable to an develop in HPV-mediated illness. Overexpression of the protein p16 on immunohistochemistry is broadly frail as a surrogate for determining HPV mediation thanks to the price and bother in enforcing HPV DNA and RNA testing.
Nonetheless, loads of patients comprise discordant biomarker scrape, and results in regards to the prognostic significance of this discordant neighborhood were contradictory, they noted.
“To the correct of our recordsdata, this multicenter, world survey represents by far the ideal effort to name the contribution of p16 and HPV biomarkers in determining prognosis in patients with oropharyngeal most cancers,” Mehanna and colleagues talked about. “In an era the establish oropharyngeal most cancers has been shown to comprise on the least two subtypes with very assorted prognoses, this recordsdata is mandatory to precisely classify this inhabitants of patients, and thereby again appropriate affected person option for de-escalation or escalation of treatment.”
This survey incorporated individual affected person recordsdata from 13 cohorts of patients (n=7,895) with oropharyngeal most cancers from just a few nations, along with the U.Good ample., Canada, Denmark, Germany, The Netherlands, and Switzerland.
Of seven,654 patients (in terms of three-fourths male) eligible for p16 and HPV prognosis, 46.5% were double-damaging, 44.3% double-sure, 3.8% were p16-/HPV+, and 5.4% were p16+/HPV-. Amongst the three,805 p16-sure patients, 10.9% did no longer display conceal presence of HPV, while of the three,849 p16-damaging patients, 7.5% showed presence of HPV.
When put next with double-sure patients, the 5-yr adjusted hazard ratios (HRs) for DFS and OS, respectively, demonstrated vastly worse survival outcomes for all assorted groups:
- Discordant (p16-/HPV+): HR 2.36 (95% CI 1.87-3.97) and HR 3.15 (95% CI 2.50-3.97)
- Discordant (p16+/HPV-): HR 1.92 (95% CI 1.42-2.60) and 2.69 (95% CI 2.21-3.29)
- Double-damaging (p16-/HPV-): HR 3.27 (95% CI 2.84-3.76) and 4.05 (95% CI 3.59-4.58)
Mehanna’s neighborhood chanced on that the prognostic patterns described above were consistent no topic the establish of Europe, the anatomical subsite, and when analyzing assorted HPV testing strategies. Nonetheless, they additionally noted that the prognosis between the just a few p16 and HPV subgroups differed vastly by smoking scrape.
OS in p16+/HPV- by no technique-people who smoke became once such as that of double-sure by no technique-people who smoke. Nonetheless, double-damaging ever-people who smoke had a much worse OS than double-sure ever-people who smoke (adjusted HR 2.94, 95% CI 2.37-3.64), though OS did no longer fluctuate from p16-/HPV+ ever-people who smoke or double-damaging ever-people who smoke.
Look for boundaries incorporated its retrospective hang and utilizing a vary of tests for p16 and HPV in step with institutional preference, although the authors argued that the latter point “may maybe maybe additionally be notion to be a energy of this survey, on anecdote of it replicates the steady-world atmosphere, by which assorted institutions would employ assorted p16 and HPV assays.”
Mike Bassett is a workers creator specializing in oncology and hematology. He is essentially based fully in Massachusetts.
The survey became once funded by the European Regional Sort Fund, Generalitat de Catalunya, National Institute for Health Analysis (NIHR) U.Good ample., Cancer Analysis U.Good ample., Medical Analysis Council (MRC) U.Good ample., the Swedish Cancer Basis, and the Stockholm Cancer Society.
Mehanna dislcosed toughen from, and/or relationships with, NIHR U.Good ample., Cancer Analysis U.Good ample., MRC U.Good ample., AstraZeneca, MSD, Merck, Nanobiotix, and Seagen, apart from as serving as director of Warwickshire Head Neck Clinic and Docspert Health.
Co-authors disclosed more than one relationships with industry.
The Lancet Oncology
Provide Reference: Mehanna H, et al “Prognostic implications of p16 and HPV discordance in oropharyngeal most cancers (HNCIG-EPIC-OPC): A multicentre, multinational, individual affected person recordsdata prognosis” Lancet Oncol 2023; DOI: 10.1016/S1470-2045(23)00013-X.