title: Human papillomavirus 16/18 E7 viral loads predict distant metastasis in oral cavity squamous cell carcinoma.
abstract: BACKGROUND
  Human papillomaviruses (HPV) seem to be related to distant metastasis (DM) in advanced oral cavity squamous cell carcinoma (OSCC) patients.
  
  
  OBJECTIVE
  This study aimed to investigate whether high-risk HPV viral load may predict DM among OSCC patients and stratify patients for risk-adapted treatment.
  
  
  METHODS
  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.
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; Department of Medical Biotechnology and Laboratory Science, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC.
authors.forename: Chung-Guei
authors.initials: CG
authors.lastname: Huang
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Li-Ang
authors.initials: LA
authors.lastname: Lee
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Kuo-Chien
authors.initials: KC
authors.lastname: Tsao
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC. Electronic address: liaoct@cgmh.org.tw.
authors.forename: Chun-Ta
authors.initials: CT
authors.lastname: Liao
authors.affiliation: Departments of Biostatistics and Informatics Unit, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Lan-Yan
authors.initials: LY
authors.lastname: Yang
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Chung-Jan
authors.initials: CJ
authors.lastname: Kang
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Kei-Ping
authors.initials: KP
authors.lastname: Chang
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Shiang-Fu
authors.initials: SF
authors.lastname: Huang
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: I-How
authors.initials: IH
authors.lastname: Chen
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Shu-Li
authors.initials: SL
authors.lastname: Yang
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Clinical Trial Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Lee
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Clinical Trial Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Chuen
authors.initials: C
authors.lastname: Hsueh
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Clinical Trial Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Tse-Ching
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Kang-Hsing
authors.initials: KH
authors.lastname: Fan
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Tung-Chieh
authors.initials: TC
authors.lastname: Chang
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Medical Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Wang
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Diagnostic Radiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Shu-Hang
authors.initials: SH
authors.lastname: Ng
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC. Electronic address: yen1110@cgmh.org.tw.
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000556:secondary / Q000821:virology; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification*; D052161:Human papillomavirus 18 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000150:complications / Q000175:diagnosis*; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D009856:Oncogene Proteins, Viral / Q000235:genetics; D050725:Papillomavirus E7 Proteins / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D019562:Viral Load
chemical_list: D004268:DNA-Binding Proteins; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: Distant metastasis; HPV; HPV 16; Oral cavity squamous cell carcinoma; Outcome; Viral load