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New quantitative test for HPV
It is known that human papilloma virus (HPV) infection can be associated with the development of cervical carcinoma in situ (CIS). However, less than 1% of women who are positive for the oncogenic types of HPV, such as HPV-16, develop CIS. Thus, HPV infection is a very poor predictive factor. It has been suggested that the amount of virus, the viral load, may be of greater predictive value. However, it has not been possible to test in a quantitative manner the amount of HPV DNA present in smear samples due to technical limitations. The advent of a new technique known as the Taqman assay has overcome some of these problems and the use of this polymerase chain reaction (PCR)-based technique to quantify the amount of HPV-16 DNA in archived Papanicolaou (PAP) smears was recently described by Josefsson and colleagues [1] in the Lancet.
The technique uses a non-extendible DNA probe, which is labelled with different fluorescent dyes at either end. When the probe is intact, the fluorescent emission from the 5' end is quenched by the fluorescent dye at the 3' end. During the PCR reaction, the exonuclease activity of the DNA polymerase can cleave the probe and the fluorescent emission from the probe is proportional to the amount of amplicon that is generated. Thus, a measure of the amount of specific genetic targets, such as HPV-16 DNA, can be obtained.
Using this technique Josefsson and co-workers carried out a nested case-control study of 478 cases (2081 smears) with CIS and 608 matched controls (1754 smears) from the general population to study the HPV-16 levels in smears collected from 1969 to 1995 in the Uppsala county of Sweden. Although the first smear samples from these women were negative cytologically, an increased risk of developing CIS was found with higher amounts of HPV-16 DNA. In fact, for women in the highest DNA group (highest 20th percentile) the risk was approximately 60-fold that of women negative for HPV-16. In a separate study [2], the same group showed that women, in particular, those who were under 25 years of age at the time of sampling, who had long-term consistently high viral loads were also at increased risk of developing CIS.
However, the authors speculate that this assay can not at present be used alone as there was a low positive predictive value for women with lower amounts of HPV-16 DNA. They also suggest testing for all the HPV-types, as only 42% of cases were positive for HPV-16, and the use of fresh, as opposed to archival, material could also improve upon the positive predictive value. This technique might, therefore, be able to replace PAP smears as HPV DNA can be detected when no cytological changes are present. As a screening test, it could also be potentially more accessible since self-collection of samples is possible. Thus, this test could be the way of the future in the identification of the subset of women who are at a higher risk of developing CIS.
Emma Cannell
A forthcoming special issue of the European Journal of Cancer will review the state of the art in screening for cervical cancer in all member states of the European Union. The content has been prepared by Dr Elena Riza, Dr Athena Linos and Dr Marjolein van Ballegooijen (Guest Editors) on behalf of the Epidemiology Group of the European Network for Cervical Cancer, and will consist of a compilation of country-specific articles followed by an overview of important quantitative cervical cancer screening outcomes. The aim of this joint work was to demonstrate the large diversity in the organisation, methodology and reporting of results among the various European screening programmes and to explore the effectiveness of new evaluation methodologies.
1Josefsson AM, Magnusson PKE, Ylitalo N, et al. Viral load of human papilloma virus 16 as a determinant for development of cervical carcinoma in situ: a nested case-control study. Lancet 2000, 355, 2189-2193.
2Ylitalo N, Sorensen P, Josefsson AM, et al. Consistent high viral load of human papillomavirus 16 and risk of cervical carcinoma in situ: a nested case-control study. Lancet 2000, 355, 2194-2198.
European Journal of Cancer
International Cancer News
Compiled by: Brad Timms (Acting News Editor)
European Journal of Cancer: 36 (2000) pp1725-1729
Copyright 2004 Published by Elsevier Ltd
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