Quantitation of human papillomavirus DNA in plasma of oropharyngeal carcinoma patients

Int J Radiat Oncol Biol Phys. 2012 Mar 1;82(3):e351-8. doi: 10.1016/j.ijrobp.2011.05.061. Epub 2011 Oct 8.

Abstract

Purpose: To determine whether human papillomavirus (HPV) DNA can be detected in the plasma of patients with HPV-positive oropharyngeal carcinoma (OPC) and to monitor its temporal change during radiotherapy.

Methods and materials: We used polymerase chain reaction to detect HPV DNA in the culture media of HPV-positive SCC90 and VU147T cells and the plasma of SCC90 and HeLa tumor-bearing mice, non-tumor-bearing controls, and those with HPV-negative tumors. We used real-time quantitative polymerase chain reaction to quantify the plasma HPV DNA in 40 HPV-positive OPC, 24 HPV-negative head-and-neck cancer patients and 10 non-cancer volunteers. The tumor HPV status was confirmed by p16(INK4a) staining and HPV16/18 polymerase chain reaction or HPV in situ hybridization. A total of 14 patients had serial plasma samples for HPV DNA quantification during radiotherapy.

Results: HPV DNA was detectable in the plasma samples of SCC90- and HeLa-bearing mice but not in the controls. It was detected in 65% of the pretreatment plasma samples from HPV-positive OPC patients using E6/7 quantitative polymerase chain reaction. None of the HPV-negative head-and-neck cancer patients or non-cancer controls had detectable HPV DNA. The pretreatment plasma HPV DNA copy number correlated significantly with the nodal metabolic tumor volume (assessed using (18)F-deoxyglucose positron emission tomography). The serial measurements in 14 patients showed a rapid decline in HPV DNA that had become undetectable at radiotherapy completion. In 3 patients, the HPV DNA level had increased to a discernable level at metastasis.

Conclusions: Xenograft studies indicated that plasma HPV DNA is released from HPV-positive tumors. Circulating HPV DNA was detectable in most HPV-positive OPC patients. Thus, plasma HPV DNA might be a valuable tool for identifying relapse.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Carcinoma, Squamous Cell / blood*
  • Carcinoma, Squamous Cell / chemistry
  • Carcinoma, Squamous Cell / therapy
  • Carcinoma, Squamous Cell / virology
  • Chemoradiotherapy
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis*
  • DNA, Viral / blood*
  • DNA, Viral / isolation & purification
  • Gene Dosage
  • Genetic Markers / genetics
  • Human papillomavirus 16 / genetics*
  • Human papillomavirus 18 / genetics*
  • Humans
  • Male
  • Mice
  • Mice, SCID
  • Middle Aged
  • Oropharyngeal Neoplasms / blood*
  • Oropharyngeal Neoplasms / chemistry
  • Oropharyngeal Neoplasms / pathology
  • Oropharyngeal Neoplasms / therapy
  • Oropharyngeal Neoplasms / virology
  • Real-Time Polymerase Chain Reaction
  • Tumor Burden
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • Genetic Markers