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Abstract
Laboratory and epidemiological research suggests an association between human papillomavirus
(HPV) and cervical intraepithelial neoplasia (CIN). We studied the natural history
of incident cervical HPV infection and its relation to the development of CIN.
We recruited 2011 women aged 15-19 years who had recently become sexually active.
We took a cervical smear every 6 months and stored samples for virological analysis.
We immediately referred all women with any cytological abnormality for colposcopic
assessment, but postponed treatment until there was histological evidence of progression
to high-grade CIN.
In 1075 women who were cytologically normal and HPV negative at recruitment, the cumulative
risk at 3 years of any HPV infection was 44% (95% CI 40-48): HPV 16 was the most common
type. The cumulative risk at 3 years of detecting an HPV type not present in the first
positive sample was 26% (20-32). 246 women had an abnormal smear during follow-up,
of whom 28 progressed to high-grade CIN. The risk of high-grade CIN was greatest in
women who tested positive for HPV 16 (risk ratio 8.5 [3.7-19.2]); this risk was maximum
6-12 months after first detection of HPV 16. All HPV types under consideration were
associated with cytologically abnormal smears. Although abnormality was significantly
less likely to be associated with low-viral-load samples, the cumulative risk at 3
years of a high-viral-load sample after a low-viral-load sample was 45% (95% CI 35-56).
Five women who progressed to high-grade CIN consistently tested negative for HPV.
Our findings suggest that attempts to exploit the association between cervical neoplasia
and HPV infection to improve effectiveness of cervical screening programmes might
be undermined by the limited inferences that can be drawn from the characterisation
of a woman's HPV status at a single point in time, and the short lead time gained
by its detection.