Detection and Quantitation of Human Papillomavirus DNA in the Plasma of Patients with Cervical Carcinoma1

  1. Seung Myung Dong,
  2. Sara I. Pai,
  3. Seo-Hee Rha,
  4. Allan Hildesheim,
  5. Robert J. Kurman,
  6. Peter E. Schwartz,
  7. Rodrigue Mortel,
  8. Larry McGowan,
  9. Mitchell D. Greenberg,
  10. Willard A. Barnes and
  11. David Sidransky2
  1. Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division [S. M. D., S. I. P., S-H. R., D. S.] and Department of Pathology [R. J. K.], Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892 [A. H.]; Yale University School of Medicine, New Haven, Connecticut [P. E. S.]; Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033 [R. M.]; George Washington University, Washington, DC 20052 [L. M.]; Graduate Hospital, Philadelphia, Pennsylvania 19146 [M. D. G.]; and Lombardi Cancer Center, Georgetown University, Washington, DC 20007 [W. A. B.]

    Abstract

    Human papillomaviruses (HPVs) play a central role in the development of cervical carcinoma. Plasma DNA from 232 patients taken at diagnosis or after treatment for invasive cervical cancer (n = 175) or carcinoma in situ (n = 57) and 60 normal controls were examined for HPV-16 or HPV-18 E7 DNA by conventional and real-time quantitative PCR assays. We found HPV-16 or HPV-18 E7 DNA in 6.9% (11 of 175) of invasive cervical cancer cases (18.1% of cases positive for HPV-16 or HPV-18 at the genital tract), 1.8% (1 of 57) of carcinoma in situ, and 1.7% (1 of 60) of normal controls by conventional PCR. Quantitative PCR identified the highest concentrations of HPV DNA (copy number of HPV/ml of plasma) in patients with invasive cervical cancer (mean, 11,163; median, 183.5), followed by a level of 8 in the single carcinoma in situ case and 0 copies in the normal control initially positive by conventional PCR. HPV DNA can be detected in the plasma of some patients with HPV-positive cervical tumors. It remains to be demonstrated whether quantitative PCR analysis of HPV DNA in plasma may have utility in patients at high risk of recurrent disease.

    Footnotes

    • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • 1 Supported by Grant U01-CA-84986 from the National Cancer Institute and R01-DE-12588 from the National Institute of Dental and Craniofacial Research.

    • 2 To whom requests for reprints should be addressed, at Department of Otolaryngology and Head and Neck Surgery, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, 818 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205-2196. E-mail: dsidrans{at}jhmi.edu

    • 3 The abbreviations used are: HPV, human papillomavirus; NPC, nasopharyngeal cancer.

      • Accepted September 29, 1901.
      • Received March 12, 1901.
      • Revision received September 7, 1901.
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