Double Positivity for HPV DNA/P16^INK4a Does Not Influence Survival of Patients With Oral Squamous Cell Carcinoma

We investigated the prevalence of human papillomavirus (HPV) in a prospective cohort of patients with squamous cell carcinoma of the oral cavity (OSCC) using both p16^INK4a and HPV DNA, i.e., double positivity, as a definition criterion. Additionally, we examined the association of HPV with survival.

Samples from 280 OSCC patients were analyzed for HPV-positivity using p16^INK4a immunohistochemistry (IHC) and in situ hybridization (ISH)/LCD arrays, for HPV low and high-risk types. Only patients positive for both p16^INK4a and HPV DNA were considered as HPV-positive. Survival probabilities and 95% confidence intervals were estimated using the Kaplan-Meier method. Cox proportional hazards models were used to assess HPV association with disease-free survival (DFS), cause-specific survival (CSS) and overall survival (OS) in a competing risks scenario.

Specimen from 30 (10.7%) patients were p16+ and HPV DNA+, while 31 (11.0%) were either p16+ or HPV DNA+ only. OS probabilities at five years for HPV-positive and -negative groups were 50.9% (35.4%-73.1%) and 52.9% (47.0%-59.5%), respectively. HPV double positivity influenced neither OS, CSS nor DFS: HR=0.84 (0.43-1.63), 1.64 (0.76-3.54) and 1.13 (0.55-2.35), respectively.

In contrast to oropharyngeal cancer, the prevalence of HPV in OSCC is low and the presence of HPV does not influence survival outcomes. Hence, there is no evidence to support a parallel transfer of therapy regimen for HPV-positive OPC to OSCC, in terms of therapy de-escalation and/or vaccination.