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. (November 2020)

• Record Type: Journal Article
• Authors: Young, Richard J.; Solomon, Benjamin; Corry, June; Angel, Christopher; Kenny, Lizbeth; Porceddu, Sandro; Wratten, Christopher; Macann, Andrew; Jackson, James E.; Herschtal, Alan; Rischin, Danny
• Is Part Of: Oral oncology. Volume 110(2020)
• Publication Date: 2020-11
• Subjects: Head and neck cancer -- Oropharyngeal cancer -- Human papillomavirus -- P16 immunohistochemistry -- HPV RNA in-situ hybridization; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2020.104988
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: Accurate HPV status crucial for enrolment in HPVOPSCC de-escalation trials. 100% concordance of local and central laboratory p16 IHC in low risk HPVOPSCC trial. 100% concordance between p16 IHC and HPV RNA ISH in low risk HPVOPSCC trial. p16 sufficient to enrol in low risk HPVOPSCC trials if pre-test probability high. Abstract: 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.