Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas

Yuxuan Wang, Simeon Springer, Carolyn L Mulvey, Natalie Silliman, Joy Schaefer, Mark Sausen, Nathan James, Eleni M Rettig, Theresa Guo, Curtis R Pickering, Justin A Bishop, Christine H Chung, Joseph A Califano, David W Eisele, Carole Fakhry, Christine G Gourin, Patrick K Ha, Hyunseok Kang, Ana Kiess, Wayne M Koch, Jeffrey N Myers, Harry Quon, Jeremy D Richmon, David Sidransky, Ralph P Tufano, William H Westra, Chetan Bettegowda, Luis A Diaz Jr, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Nishant Agrawal, Yuxuan Wang, Simeon Springer, Carolyn L Mulvey, Natalie Silliman, Joy Schaefer, Mark Sausen, Nathan James, Eleni M Rettig, Theresa Guo, Curtis R Pickering, Justin A Bishop, Christine H Chung, Joseph A Califano, David W Eisele, Carole Fakhry, Christine G Gourin, Patrick K Ha, Hyunseok Kang, Ana Kiess, Wayne M Koch, Jeffrey N Myers, Harry Quon, Jeremy D Richmon, David Sidransky, Ralph P Tufano, William H Westra, Chetan Bettegowda, Luis A Diaz Jr, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Nishant Agrawal

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.

Conflict of interest statement

Competing interests: Under agreements between the JHU, Genzyme, Sysmex-Inostics, Qiagen, Invitrogen, and Personal Genome Diagnostics, L.D., N.P., B.V., and K.W.K. are entitled to a share of the royalties received by the University on sales of products related to genes and technologies described in this manuscript. L.D., N.P., B.V., and K.W.K. are co-founders of Personal Genome Diagnostics and PapGene Inc., are members of the Scientific Advisory Boards of Sysmex-Inostics, Personal Genome Diagnostics, and PapGene Inc., and own Personal Genome Diagnostics and PapGene Inc. stock, which is subject to certain restrictions under Johns Hopkins University policy. The terms of these arrangements are managed by the Johns Hopkins University in accordance with its conflict-of-interest policies. Additionally, B.V. and K.W.K. are on the Scientific Advisory Board of Morphotek Inc., and N.J. is affiliated with the Emmes Corporation.

Copyright © 2015, American Association for the Advancement of Science.

Figures

Fig. 1. Schematic showing the shedding of…
Fig. 1. Schematic showing the shedding of tumor DNA from head and neck cancers into the saliva or plasma
Tumors from various anatomic locations shed DNA fragments containing tumor-specific mutations and HPV DNA into the saliva or the circulation. The detectability of tumor DNA in the saliva varied with anatomic location of the tumor, with the highest sensitivity for oral cavity cancers. The detectability in plasma varied much less in regard to the tumor’s anatomic location.

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