ArticlesNatural history of cervical human papillomavirus infection in young women: a longitudinal cohort study
Introduction
Laboratory-based research has firmly established a role for human papillomavirus (HPV) infection in cervical cancer. The epidemiological evidence that lends support to this finding is largely based on case-control studies, which have consistently revealed a strong association between cervical neoplasia and the detection of HPV DNA in samples of exfoliated cervical cells taken at, or subsequent to, diagnosis of disease.1 However, there is always ambiguity about the temporal relation between exposure and outcome with case-control studies, which, for example, does not allow us to eliminate the possibility that the presence of disease could itself increase the ability to detect HPV.2 Only cohort studies that include women who are cytologically normal at enrolment can provide direct evidence of temporality. Even with these studies, however, time of onset of infection has to be known to describe the incubation curve for HPV-associated abnormality; this detail cannot be established when the cohort includes women who are HPV positive on study entry, because the duration of infection before recruitment is unknown. To address this issue we recruited a cohort of young women who had recently become sexually active and were therefore unlikely to have had a previous cervical HPV infection. Here we describe the natural history of incident HPV infection and its temporal relation to the occurrence of cytological abnormality and development of high-grade cervical intraepithelial neoplasia (CIN).
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Patients
We recruited women aged 15–19 years who visited one Birmingham Brook Advisory Centre between 1988 and 1992. The women were likely to be available for long-term follow-up because of their continuing need for contraceptive supplies. At study entry, we obtained a detailed social, sexual, and behavioural risk-factor profile for each participant and took a cervical smear. We stored cervical and serum samples for future virological testing. We asked women to reattend at intervals of 6 months when we
Results
We enrolled 2011 women, 530 (26%) of whom were excluded from analyses because they had abnormal smears (148) or were HPV positive on study entry (244), or both (138). We also excluded 406 women who gave only one sample that could be tested both cytologically and virologically. The final cohort comprises 1075 women who were cytologically normal and HPV negative on study entry and who had more than one evaluable sample. Table 1 shows baseline characteristics of our cohort at study entry. The
Discussion
As far as we know, this is the first cohort study to describe the natural history of incident cervical HPV infection in a UK population. The prevalence at recruitment and the incidence of HPV infection in our population were high. Our estimate of the cumulative risk at 3 years is similar to that reported for a cohort of North American college students, where HPV 16 was also the most common infecting type.9 We intended to recruit women before, or soon after, they had become sexually active, to
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