ArticlesConsistent high viral load of human papillomavirus 16 and risk of cervical carcinoma in situ: a nested case-control study
Introduction
Viral persistence of oncogenic human papillomaviruses (HPV) seems essential for the development of cervical neoplasia. A high viral load resulting from productive viral replication might support viral persistence.1 All studies but one that have estimated HPV load, have shown an increased risk for cervical carcinoma in relation to high viral load.2, 3, 4, 5, 6, 7 These investigations did not, however, quantify viral load, which was estimated crudely from the signal intensity in the hybridisation assay or by comparison of results from different HPV detection methods. We did a nested case-control study to investigate the temporal relation between HPV 16 load and cervical carcinoma in situ by quantitative PCR assay to try to achieve better understanding of the role of HPV load in the development of cervical carcinoma.
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Participants
We selected women from a cohort in a cytological screening programme that covered women aged 30–49 years (and, later, 25-49 years), started in Uppsala County, Sweden in 1967.8 732 287 smears from 146 889 women were stored at the University Hospital, and all information was stored on computer from 1969 to 1995. From this cytology register we identified all registered women who had at least one smear. We required that the first smear was cytologically normal (PAP=1) and that the women were born
Characteristics of participants
462 smears for cases and 386 smears for controls were excluded because of negative β-actin Ct values. Therefore, 2081 smears from the cases and 1754 smears from the controls were analysed (table 1). 871 (42%) smears were HPV 16 positive among cases and 117 (7%) among controls. The median β-actin Ct values were similar at different times before diagnosis (table 1), with no change over time.15 By contrast, the median HPV 16 Ct values were strikingly lower (indicating high viral load) in cases
Discussion
Viral load of HPV 16 determines a woman's risk of developing cervical carcinoma in situ many years in advance of the event. A substantial excess risk could already be predicted in women with a high viral load of HPV 16a decade before diagnosis of cervical carcinoma in situ, compared with HPV-16-negative women. By contrast, women with low viral load of HPV 16 were not at increased risk of cervical carcinoma in situ. Quantitative measurement of low, medium, high, and no HPV 16 viral load added
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