Human papillomavirus 16/18 E7 viral loads predict distant metastasis in oral cavity squamous cell carcinoma

J Clin Virol. 2014 Oct;61(2):230-6. doi: 10.1016/j.jcv.2014.07.007. Epub 2014 Jul 22.


Background: Human papillomaviruses (HPV) seem to be related to distant metastasis (DM) in advanced oral cavity squamous cell carcinoma (OSCC) patients.

Objectives: This study aimed to investigate whether high-risk HPV viral load may predict DM among OSCC patients and stratify patients for risk-adapted treatment.

Study design: Viral loads of E7 oncogenes for HPV 16/18 were measured by quantitative PCR tests in paraffin-embedded lesional specimens from 312 OSCC of which the HPV genotypes had been determined previously. Multivariable Cox regression analysis was used to identify the independent prognostic factors for 5-year DM and C statistics were further computed.

Results: By multivariable analysis, high HPV 16 E7 viral load (≥15.0 copies/genome); high HPV 18 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. We further identified three prognostic groups. In the high-risk group (level IV/V metastases or high HPV 16/18 E7 viral load plus pN2, tumor depth ≥11 mm, or ECS), the 5-year distant metastasis rate was 74%. In the intermediate-risk group (high HPV 16/18 E7 viral load, pN2, tumor depth ≥11 mm, or ECS), the 5-year DM rate was 17%. Finally, the 5-year DM rate was 1% in the low-risk group (no risk factors). The value of the C statistics was 0.78.

Conclusions: Among OSCC patients, high HPV 16/18 E7 viral load identifies a small subgroup of patients at high-risk of 5-year DM and suggest the need for more intensive treatments and follow-up strategies.

Keywords: Distant metastasis; HPV; HPV 16; Oral cavity squamous cell carcinoma; Outcome; Viral load.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / virology
  • DNA-Binding Proteins / genetics
  • Female
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / isolation & purification*
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / isolation & purification*
  • Humans
  • Male
  • Middle Aged
  • Mouth Neoplasms / complications
  • Mouth Neoplasms / diagnosis*
  • Neoplasm Metastasis / diagnosis*
  • Oncogene Proteins, Viral / genetics
  • Papillomavirus E7 Proteins / genetics
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Viral Load*


  • DNA-Binding Proteins
  • E7 protein, Human papillomavirus type 18
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • oncogene protein E7, Human papillomavirus type 16