Methods for Detecting Papillomavirus DNA in Blood Plasma and Serum

Abstract

This invention relates to the detection of extracellular papillomavirus DNA in blood plasma or serum from a human or animal. In particular, the invention relates to the detection, identification, evaluation, or monitoring of neoplastic, premalignant or malignant disease associated with a papillomavirus. The invention thereby provides methods for the identification of individuals at risk for, or having, cervical dysplasia, cervical intraepithelial neoplasia, or cervical cancer.

Description

[0001]This application is a continuation-in-part of U.S. patent application Ser. No. 09 / 456,222, filed Dec. 7, 1999, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 049,234, filed Mar. 27, 1998, which is a continuation-in-part of U.S. patent application Ser. No. 08 / 818,058, filed Mar. 14, 1997, which is a continuation-in-part of U.S. Provisional Application Ser. No. 60 / 028,180, filed Oct. 15, 1996, which is a continuation-in-part of U.S. Provisional Application Ser. No. 60 / 026,252, filed Sep. 17, 1996, which is a continuation-in-part of U.S. Provisional Application Ser. No. 60 / 013,497, filed Mar. 15, 1996, the entire disclosure of each of the foregoing is hereby incorporated by reference.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]This invention relates to methods for detecting specific extracellular nucleic acid in plasma or serum fractions of human or animal blood associated with neoplastic or proliferative disease. Specifically, the inve...

AI Technical Summary

Benefits of technology

The present invention provides methods for detecting papillomavirus nucleic acid in bodily fluids, such as blood or plasma, for diagnosis, monitoring, or evaluation of neoplastic disease. The methods involve extracting the nucleic acid from the fluid, amplifying a portion of the nucleic acid, and detecting the amplified product. The invention also provides a diagnostic kit for detecting papillomavirus nucleic acid in bodily fluids. The technical effect of the invention is to provide a reliable and sensitive method for detecting papillomavirus nucleic acid in bodily fluids, which can be used for diagnosis, monitoring, or evaluation of neoplastic disease.

Problems solved by technology

Unfortunately, the Pap smear does not detect all instances of cervical dysplasia or premalignancy.

In an additional 20-30% of cases, the Pap smear may be insufficient for interpretation due to the presence of inflammatory cells.

However, HPV infection cannot be detected in all cases of cervical dysplasia / pre-malignancy or even of cervical carcinoma.

Unfortunately, this method identifies both individuals with prior HPV exposure but without persistent infection and those with persistent infection, but does not distinguish between ongoing, persistent, and chronic HPV infections.

Serologic testing for HPV antibodies thus does not correlate well with the presence of cervical dysplasia, because it does not permit discrimination between previous HPV exposure and persistent HPV infection (Olsen et al., 1996, Int. J. Cancer 68: 415-419).

This method is disadvantageous because the examiner may miss an infected region of the cervix, or the infected lesion may not be superficial and readily accessible, so that the test provides a false-negative result.

Furthermore, as this method of testing for HPV DNA requires a gynecologic exam, DNA testing of cervical smears remains an imperfect method of screening the general female population because such exams are avoided by many women despite medical recommendations to the contrary.

Direct tissue swabs of the male urethra are not an effective general screening approach for detecting such carriers in the male population.

However, it is not known in the art that papillomavirus DNA can be detected in the blood of individuals without cancer.

Further, it is not known to the art whether papilloma virus can be detected in plasma and serum as an indication of persistent infection or risk for dysplasia or carcinoma.

To the contrary, the prior art suggests that some viruses are not readily detectable in the blood of infected individuals.

This makes screening of women for the HPV virus doubly impractical, since any such screening would most likely be performed well beyond the period of initial exposure to the virus in the majority of cases.

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