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

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.]

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.

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