title: Saliva and plasma quantitative polymerase chain reaction-based detection and surveillance of human papillomavirus-related head and neck cancer.
abstract: OBJECTIVE
  Human papillomavirus type 16 (HPV-16) is a major causative factor in oropharyngeal squamous cell carcinoma (OPSCC). The detection of primary OPSCC is often delayed owing to the challenging anatomy of the oropharynx.
  
  
  OBJECTIVE
  To investigate the feasibility of HPV-16 DNA detection in pretreatment and posttreatment plasma and saliva and its potential role as a marker of prognosis.
  
  
  METHODS
  This is a retrospective analysis of a prospectively collected cohort. Among a cohort of patients with oropharyngeal and unknown primary squamous cell carcinoma with known HPV-16 tumor status from the Johns Hopkins Medical Institutions and Greater Baltimore Medical Center (from 1999 through 2010), 93 patients were identified with a complete set of pretreatment and posttreatment plasma or saliva samples, of which 81 patients had HPV-16-positive tumors and 12 patients had HPV-16-negative tumors. Real-time quantitative polymerase chain reaction was used to detect HPV-16 E6 and E7 DNA in saliva and plasma samples.
  
  
  METHODS
  Main outcomes included sensitivity, specificity, negative predictive value of combined saliva and plasma pretreatment HPV-16 DNA status for detecting tumor HPV-16 status, as well as the association of posttreatment HPV DNA status with clinical outcomes, including recurrence-free survival and overall survival.
  
  
  RESULTS
  The median follow-up time was 49 months (range, 0.9-181.0 months). The sensitivity, specificity, negative predictive value, and positive predictive value of combined saliva and plasma pretreatment HPV-16 DNA status for detecting tumor HPV-16 status were 76%, 100%, 42%, and 100%, respectively. The sensitivities of pretreatment saliva or plasma alone were 52.8% and 67.3%, respectively. In a multivariable analysis, positive posttreatment saliva HPV status was associated with higher risk of recurrence (hazard ratio [HR], 10.7; 95% CI, 2.36-48.50) (P = .002). Overall survival was reduced among those with posttreatment HPV-positive status in saliva (HR, 25.9; 95% CI, 3.23-208.00) (P = .002) and those with HPV-positive status in either saliva or plasma but not among patients with HPV-positive status in plasma alone. The combined saliva and plasma posttreatment HPV-16 DNA status was 90.7% specific and 69.5% sensitive in predicting recurrence within 3 years.
  
  
  CONCLUSIONS
  Using a combination of pretreatment plasma and saliva can increase the sensitivity of pretreatment HPV-16 status as a tool for screening patients with HPV-16-positive OPSCC. In addition, analysis of HPV-16 DNA in saliva and plasma after primary treatment may allow for early detection of recurrence in patients with HPV-16-positive OPSCC.
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors: Sun M
authors: SM
authors: Ahn
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors: Jason Y K
authors: JY
authors: Chan
authors: Division of Biostatics and Bioinformatics, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors: Zhe
authors: Z
authors: Zhang
authors: Division of Biostatics and Bioinformatics, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors: Hao
authors: H
authors: Wang
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors: Zubair
authors: Z
authors: Khan
authors: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors: Justin A
authors: JA
authors: Bishop
authors: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors: William
authors: W
authors: Westra
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors: Wayne M
authors: WM
authors: Koch
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland4Milton J. Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland.
authors: Joseph A
authors: JA
authors: Califano
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis*; D042241:Early Diagnosis; D005240:Feasibility Studies; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D009856:Oncogene Proteins, Viral / Q000032:analysis; D009959:Oropharyngeal Neoplasms / Q000401:mortality / Q000821:virology*; D030361:Papillomavirus Infections / Q000097:blood / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012463:Saliva / Q000821:virology*; D012680:Sensitivity and Specificity
chemical_list: D004279:DNA, Viral; D009856:Oncogene Proteins, Viral