Author:
Simoens Cindy,Gheit Tarik,Ridder Ruediger,Gorbaslieva Ivana,Holzinger Dana,Lucas Eric,Rehm Susanne,Vermeulen Peter,Lammens Martin,Vanderveken Olivier M.,Kumar Rekha Vijay,Gangane Nitin,Caniglia Alessandro,Maffini Fausto,Rubio Maria Belén Lloveras,Anantharaman Devasena,Chiocca Susanna,Brennan Paul,Pillai Madhavan Radhakrishna,Sankaranarayanan Rengaswamy,Bogers Johannes,Pawlita Michael,Tommasino Massimo,Arbyn Marc,Carreira Christine,McKay-Chopin Sandrine,Jayshree Rudrapatna S.,Sabitha Kortikere S.,Shenoy Ashok M.,Zito Alfredo,Chiesa Fausto,Tagliabue Marta,Ansarin Mohssen,Sankaran Subha,Herold-Mende Christel,Dyckhoff Gerhard,Mosialos George,Boeing Heiner,Castellsagué Xavier,Sanjosé Silvia de,Mena Marisa,Bosch Francesc Xavier,Alemany Laia,Esmy Pulikottil Okkuru,Vijayakumar Manavalan,Chiwate Aruna S.,Thorat Ranjit V.,Hublikar Girish G.,Lakshetti Shashikant S.,Nene Bhagwan M.,Kataki Amal Ch.,Das Ashok Kumar,Ramadas Kunnambath,Somanathan Thara,
Abstract
Abstract
Background
The incidence of high-risk human papillomavirus (hrHPV)-driven head and neck squamous cell carcinoma, in particular oropharyngeal cancers (OPC), is increasing in high-resource countries. Patients with HPV-induced cancer respond better to treatment and consequently have lower case-fatality rates than patients with HPV-unrelated OPC. These considerations highlight the importance of reliable and accurate markers to diagnose truly HPV-induced OPC.
Methods
The accuracy of three possible test strategies, i.e. (a) hrHPV DNA PCR (DNA), (b) p16(INK4a) immunohistochemistry (IHC) (p16), and (c) the combination of both tests (considering joint DNA and p16 positivity as positivity criterion), was analysed in tissue samples from 99 Belgian OPC patients enrolled in the HPV-AHEAD study. Presence of HPV E6*I mRNA (mRNA) was considered as the reference, indicating HPV etiology.
Results
Ninety-nine OPC patients were included, for which the positivity rates were 36.4%, 34.0% and 28.9% for DNA, p16 and mRNA, respectively. Ninety-five OPC patients had valid test results for all three tests (DNA, p16 and mRNA). Using mRNA status as the reference, DNA testing showed 100% (28/28) sensitivity, and 92.5% (62/67) specificity for the detection of HPV-driven cancer. p16 was 96.4% (27/28) sensitive and equally specific (92.5%; 62/67). The sensitivity and specificity of combined p16 + DNA testing was 96.4% (27/28) and 97.0% (65/67), respectively. In this series, p16 alone and combined p16 + DNA missed 1 in 28 HPV driven cancers, but p16 alone misclassified 5 in 67 non-HPV driven as positive, whereas combined testing would misclassify only 2 in 67.
Conclusions
Single hrHPV DNA PCR and p16(INK4a) IHC are highly sensitive but less specific than using combined testing to diagnose HPV-driven OPC patients. Disease prognostication can be encouraged based on this combined test result.
Funder
European Commission
Investigator Initiated Studies Program of Merck Sharp & Dohme Corp
Horizon 2020 Framework Programme for Research and Innovation of the European Commission
the Belgian Foundation Against Cancer
Publisher
Springer Science and Business Media LLC