Natural history of cervical human papillomavirus infection in young women:a longitudinal cohort study

Background 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. Methods We recruited 2011 women aged 15-19 years who had recently become se xually active. We took a cervical smear every 6 months and stored samples f or virological analysis. We immediately referred all women with any cytolog ical abnormality for colposcopic assessment, out postponed treatment until there was histological evidence of progression to high-grade CIN. Findings IN 1075 women who were cytologically normal and HPV negative at re cruitment, 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 progr essed to high-grade CIN. The risk of high-grade CIN was greatest in women w ho tested positive for HPV 16 (risk ratio 8.5 [3.7-19.2]); this risk was ma ximum 6-12 months after first detection of HPV 16. All HPV types under cons ideration were associated with cytologically abnormal smears. Although abno rmality 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. Interpretation Our findings suggest that attempts to exploit the associatio n 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 s ingle point in time, and the short lead time gained by its detection.