title: Quantitation of human papillomavirus DNA in plasma of oropharyngeal carcinoma patients.
abstract: OBJECTIVE
  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
  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.
authors: Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305-5847, USA.
authors: Hongbin
authors: H
authors: Cao
authors: Alice
authors: A
authors: Banh
authors: Shirley
authors: S
authors: Kwok
authors: Xiaoli
authors: X
authors: Shi
authors: Simon
authors: S
authors: Wu
authors: Trevor
authors: T
authors: Krakow
authors: Brian
authors: B
authors: Khong
authors: Brindha
authors: B
authors: Bavan
authors: Rajeev
authors: R
authors: Bala
authors: Benjamin A
authors: BA
authors: Pinsky
authors: Dimitrios
authors: D
authors: Colevas
authors: Nader
authors: N
authors: Pourmand
authors: Albert C
authors: AC
authors: Koong
authors: Christina S
authors: CS
authors: Kong
authors: Quynh-Thu
authors: QT
authors: Le
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000737:chemistry / Q000628:therapy / Q000821:virology; D059248:Chemoradiotherapy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D004279:DNA, Viral / Q000097:blood* / Q000302:isolation & purification; D018628:Gene Dosage; D005819:Genetic Markers / Q000235:genetics; D052162:Human papillomavirus 16 / Q000235:genetics*; D052161:Human papillomavirus 18 / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000097:blood* / Q000737:chemistry / Q000473:pathology / Q000628:therapy / Q000821:virology; D060888:Real-Time Polymerase Chain Reaction; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D005819:Genetic Markers