Human Papillomavirus‐16 E7 Viral Load Predicts Distant Metastasis in Oral Cavity Squamous Cell Carcinoma

Abstract

Objectives: Human papillomaviruses (HPV) seem to be related to distant metastasis (DM) in advanced oral cavity squamous cell carcinoma (OSCC) patients. The objective of this study was to investigate whether high-risk HPV viral load may predict DM among patients with OSCC and stratify patients for risk-adapted treatment. Methods: We measured viral load of E7 oncogenes for HPV-16 and HPV-18 by quantitative PCR tests in paraffin-embedded surgical specimens from 312 OSCC of which the HPV genotypes had been determined previously. Multivariable regression analysis was used to identify the independent prognostic factors for 5-year DM. Results: Only the HPV-16 E7 viral load was a significant adverse predictor of 5-year DM. By multivariable analysis, high HPV-16 E7 viral load (≥15.0 copies/genome); pathological N2 status (pN2); tumor depth ≥11 mm; extracapsular spread (ECS); and level IV/V metastases were independent risk factors for DM and identified 3 prognostic groups. In the high-risk group (level IV/V metastases or high HPV-16 E7 viral load plus pN2, tumor depth ≥11 mm, or ECS), the 5-year DM rate was 77.5%. In the intermediate-risk group (high HPV-16 E7 viral load, pN2, tumor depth ≥11 mm, or ECS), the 5-year DM rate was 17.8%. Finally, the 5-year DM rate was 1.3% in the low-risk group (no risk factors). Conclusions: Among OSCC patients, a high HPV-16 E7 viral load and the presence of specific pathological risk factor(s) identify a subgroup of patients at high-risk of 5-year DM. These subjects may benefit from a more intensive follow-up program and aggressive therapeutic strategies.