Validation of local p16 testing for determination of human papilloma virus status eligibility on a low risk oropharyngeal cancer trial - A Trans-Tasman Radiation Oncology Group study.

Objective: Accurate determination of human papilloma virus (HPV) status is critical when identifying patients with oropharyngeal squamous cell carcinoma (OPSCC) who may be candidates for de-escalation trials. In this study we investigated whether local p16 screening, by immunohistochemistry (IHC), has high positive predictive value (PPV) for HPV status in a good prognosis HPV positive OPSCC (HPVOPSCC) population treated on a clinical trial.
Methods and Materials: Patients enrolled on the TROG 12.01 randomised trial for good prognosis HPVOPSCC were randomised based on local p16 IHC testing but subsequently had central p16 IHC and HPV RNA in situ hybridisation (HPV RNA ISH) testing. Correlations between the local and central p16 and central HPV RNA ISH were studied. The main outcome was the positive predictive value (PPV) of local pathology laboratory testing of p16.
Results: 176/182 patients had samples available for central testing. 172/176 were evaluable for central testing of p16, and all were confirmed to be p16 positive (172/172, 100%, 95% CI = [97.9%, 100%]). Similarly, 100% of those evaluable for HPV RNA ISH (155/155, 100%, 95% CI = [97.6%, 100%]) were confirmed HPV positive, indicating p16 overexpression driven by transcriptionally active HPV and a PPV of 100% for local p16 testing.
Conclusions: Our results validate the suitability of local pathology laboratory p16 testing alone, in populations with a high attributable fraction of OPSCC due to HPV, to screen and enrol low risk HPVOPSCC patients onto de-intensification trials. This obviates the need for upfront more complex and expensive HPV assays and/or central laboratory testing.
Competing Interests: Declaration of Competing Interests Richard Young - institutional grant from Roche; Ben Solomon - personal fees from Merck Sharp & Dohme, personal fees from Bristol-Myers Squibb, grants and personal fees from Roche, grants from Regeneron, personal fees from AstraZeneca, grants and personal fees from Pfizer, personal fees from Genentech, personal fees from Loxo Oncology; Christopher Angel - institutional grant from Roche; Sandro Porceddu - personal fees from Merck Sharp & Dohme, personal fees from Merck, personal fees from Celgene; Danny Rischin - grants from Merck Sharp & Dohme, grants from Merck, grants from Bristol-Myers Squibb, grants from GSK, grants from Roche, grants from Regeneron, grants from Amgen, grants and personal fees from MSD, Trial Steering Committees and/or Advisory Boards (all uncompensated) - MSD, Merck, Bristol-Myers Squibb, GSK, Regeneron; June Corry, Christopher Wratten, Andrew Macann, James Jackson, and Alan Herschtal - no disclosures.
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