The use of p16INK4a (p16) immunostaining alone, as compared with dual p16 immunostaining and human papillomavirus (HPV) DNA detection, may result in misclassification of patients with oropharyngeal cancer (OPC) according to a large comprehensive analysis presented at the ESMO Virtual Congress 2020 by Miren Taberna of the Medical Oncology Department, Head and Neck Cancer Unit, Institut Català d'Oncologia-Hospital Duran i Reynals in Barcelona, Spain.
Dr. Taberna and colleagues used dual determination to define the clinical aspects and prognosis in patients with OPC who are positive for p16 but HPV DNA–negative (p16+/HPV-). This subset of patients has been less well studied and their prognosis remains unclear, according to the authors.
The study population consisted of 7702 patients from 9 separate countries (13 cohorts) with information regarding p16, HPV, demographics, tobacco/alcohol use and clinical data. The investigators performed this centralised individual patient data reanalysis using multivariate models to evaluate factors associated with HPV status as defined by different HPV-assessment methods. Proportional-hazards models were used to compare the risk of death among patients with HPV-related and un-related OPC.
Patients with p16+/HPV- OPC are relatively rare
The investigators determined that 49.7% of study participants were positive for p16; and 44.3% of patients were p16+/HPV+.
However, among study cases overall, 10.9% of p16+ cases were negative for HPV (p16+/HPV-).
This proportion of discordant samples (p16+/HPV-) differed significantly by geographic area (p < 0.001) and was lowest in the areas of highest HPV Attributable Fraction. For example, in North America, as represented by Toronto, Canada cohort had 186 OPC cases, of which 135 were p16+ and of those, 2 (1.5%) were p16+/HPV-.
On the contrary regarding Southern Europe, as represented by Barcelona, Spain cohort had 861 OPC cases, of which 95 were p16+, of those 28 (29%) were HPV-.
Compared with p16-/HPV- tumours, p16+/HPV+ emerged as the combination of biomarkers with the strongest prognostic value for overall survival (5-y OS; adjusted hazard ratio [aHR] 0.25; 95% confidence interval [CI] 0.22-0.28), followed by p16+/HPV- (aHR 0.64; 95% CI 0.54-0.76), and p16-/HPV+ (HR 0.65; 95% CI 0.53-0.79). Similar results were obtained for 5-y disease free survival (DFS) and 5-y specific cumulative hazard of oropharyngeal cancer death.
Conclusions
From OS and DFS data presented at the congress, the authors concluded that p16+/HPV+ tumours showed the highest OS and DFS magnitude of association compared with other biomarker combinations.
Using p16 immunostaining alone, 11% of OPC patients would be incorrectly classified as having HPV-related OPC disease according to TNM-8 staging, resulting in risk of misclassification for de-escalation in clinical trials, particularly in regions with lower attributable fractions of HPV.
p16 and HPV DNA detection should be evaluated to assess HPV in OPC in the clinical practice.
Reference
911O – Taberna M, Mehanna H, Tous S, et al. Performance of dual p16 and HPV testing for determining prognosis in cancer of the oropharynx, the EPIC-OPC Study. ESMO Virtual Congress 2020.