Plasma human papillomavirus (HPV)-DNA level was measured to evaluate the clinical usefulness of circulating DNA for cervical cancer management. DNA extracted from pretreatment plasma of 50 cervical cancer patients and from serial longitudinal plasma of 21 patients was quantified for HPV16/HPV18 by means of quantitative polymerase chain reaction. Another 15 patients with low-grade lesion (LG), 18 patients with high-grade lesion (HG), and 96 normal individuals were studied as controls. Plasma HPV16-DNA was detectable in 50% of cancer patients. The incidence and median level were statistically higher than those in LG patients and normal, but similar to HG patients. Plasma HPV18-DNA was only detected in 6% of cancer patients and 1% of normal. Same type of HPV present in plasma was also detected in its primary tumor; and the level of plasma HPV16-DNA was dependent on the viral load in primary tumor. Plasma HPV-DNA was not detected in 16 of 21 patients after treatment, and those patients had complete response to therapy. HPV-DNA persisted or reappeared in five patients after treatment (one had persistent disease and another had recurrence). Plasma HPV-DNA might be a valuable marker for monitoring therapeutic response and disease progression in cervical cancer.