Type specific persistence of high risk human papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study

doi:10.1136/bmj.325.7364.572

BMJ 2002;325:572 ( 14 September )

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Type specific persistence of high risk human papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study

Susanne K Kjaer, senior investigator, ^a Adriaan J C van den Brule, molecular biologist, ^b Gerson Paull, assistant professor, ^c Edith I Svare, senior research fellow, ^a Mark E Sherman, senior research fellow, ^d Birthe L Thomsen, senior statistician, ^a Mette Suntum, statistician, ^a Johannes E Bock, professor of gynecology, ^e Paul A Poll, pathologist, ^f Chris J L M Meijer, professor of pathology. ^b

^a Danish Cancer Society, Institute of Cancer Epidemiology, DK-2100 Copenhagen, Denmark, ^b Department of Pathology, Section of Molecular Pathology, University Hospital Vrije Universiteit, Amsterdam, Netherlands, ^c Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA, ^d Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA, ^e Department of Gynecology, Rigshospitalet, Copenhagen, Denmark, ^f Department of Pathology, Nykøbing Falster Hospital, Nykøbing Falster, Denmark

Correspondence to: S K Kjær susanne{at}cancer.dk

Objectives: To investigate the role of human papillomavirus(HPV) in the development of cervical neoplasia in women with noprevious cervical cytological abnormalities; whether the presenceof virus DNA predicts development of squamous intraepitheliallesion; and whether the risk of incident squamous intraepitheliallesions differs with repeated detection of the same HPV type versusrepeated detection of differenttypes.
Design: Population based prospective cohortstudy.
Setting: General population in Copenhagen,Denmark.
Participants: 10 758 women aged 20-29 years followed upfor development of cervical cytological abnormalities; 370 incidentcases were detected (40 with atypical squamous cells of undeterminedsignificance, 165 with low grade squamous intraepithelial lesions,165 with high grade squamous intraepitheliallesions).
Main outcome measures: Results of cervical smear tests and cervicalswabs at enrolment and at the second examination about two yearslater.
Results: Compared with women who were negative forhuman papillomavirus at enrolment, those with positive resultshad a significantly increased risk at follow up of having atypicalcells (odds ratio 3.2, 95% confidence interval 1.3 to 7.9), lowgrade lesions (7.5, 4.8 to 11.7), or high grade lesions (25.8,15.3 to 43.6). Similarly, women who were positive for HPV at thesecond examination had a strongly increased risk of low (34.3,17.6 to 67.0) and high grade lesions (60.7, 25.5 to 144.0). Forhigh grade lesions the risk was strongly increased if the samevirus type was present at both examinations (813.0, 168.2 to 3229.2).
Conclusions: Infection with human papillomavirus precedesthe development of low and high grade squamous intraepitheliallesions. For high grade lesions the risk is greatest in womenpositive for the same type of HPV on repeatedtesting.

What is already known on this topic
Persistence of infection with human papillomavirus (HPV) is thought to have a role in the development of cervical neoplasia

Previous studies have included only a few cases of high grade squamous intraepithelial lesions, and few have randomly sampled women from the general population

What this study adds
In women aged 20-29, HPV infection preceded the development of high grade lesions

Persistent HPV infection with a specific HPV type was an indicator of incident high grade lesions among young women in the general population

The association between persistence and high grade cervical lesions was more pronounced among women aged over 25

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