title: Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas.
abstract: To explore the potential of tumor-specific DNA as a biomarker for head and neck squamous cell carcinomas (HNSCC), we queried DNA from saliva or plasma of 93 HNSCC patients. We searched for somatic mutations or human papillomavirus genes, collectively referred to as tumor DNA. When both plasma and saliva were tested, tumor DNA was detected in 96% of 47 patients. The fractions of patients with detectable tumor DNA in early- and late-stage disease were 100% (n = 10) and 95% (n = 37), respectively. When segregated by site, tumor DNA was detected in 100% (n = 15), 91% (n = 22), 100% (n = 7), and 100% (n = 3) of patients with tumors of the oral cavity, oropharynx, larynx, and hypopharynx, respectively. In saliva, tumor DNA was found in 100% of patients with oral cavity cancers and in 47 to 70% of patients with cancers of the other sites. In plasma, tumor DNA was found in 80% of patients with oral cavity cancers, and in 86 to 100% of patients with cancers of the other sites. Thus, saliva is preferentially enriched for tumor DNA from the oral cavity, whereas plasma is preferentially enriched for tumor DNA from the other sites. Tumor DNA in saliva was found postsurgically in three patients before clinical diagnosis of recurrence, but in none of the five patients without recurrence. Tumor DNA in the saliva and plasma appears to be a potentially valuable biomarker for detection of HNSCC.
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Simeon
authors.initials: S
authors.lastname: Springer
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Mulvey
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Silliman
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Joy
authors.initials: J
authors.lastname: Schaefer
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Personal Genome Diagnostics, Baltimore, MD 21224, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Sausen
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: James
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Eleni M
authors.initials: EM
authors.lastname: Rettig
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Theresa
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA.
authors.forename: Curtis R
authors.initials: CR
authors.lastname: Pickering
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Bishop
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Christine H
authors.initials: CH
authors.lastname: Chung
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Milton J. Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, MD 21204, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Eisele
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Milton J. Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, MD 21204, USA.
authors.forename: Carole
authors.initials: C
authors.lastname: Fakhry
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Christine G
authors.initials: CG
authors.lastname: Gourin
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Milton J. Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, MD 21204, USA.
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Ha
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Hyunseok
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Kiess
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Koch
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Myers
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Harry
authors.initials: H
authors.lastname: Quon
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Richmon
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Tufano
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Chetan
authors.initials: C
authors.lastname: Bettegowda
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Nickolas
authors.initials: N
authors.lastname: Papadopoulos
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. nagrawal@jhmi.edu vogelbe@jhmi.edu.
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. nagrawal@jhmi.edu vogelbe@jhmi.edu.
authors.forename: Nishant
authors.initials: N
authors.lastname: Agrawal
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000235:genetics / Q000821:virology*; D004273:DNA, Neoplasm / Q000097:blood; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000235:genetics / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000502:physiology*; D012463:Saliva / Q000821:virology*
chemical_list: D004273:DNA, Neoplasm