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Persistently high loads of human papillomavirus 16 over time were associated with an increased risk for cervical cancer

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 QUESTION: In women with a first normal cervical smear, what is the temporal relation between human papillomavirus (HPV)-16 infection and cervical carcinoma in situ (CIS)?


Nested case control study of 146 889 women screened from 1969 to 1995.


Uppsala County, Sweden.


Women who were <50 years of age at entry (time of first registered smear); were born in Sweden; and had ≥1 cervical smear, a normal first smear, and smears containing β actin. The case group consisted of women who had CIS (n=478; 2081 smears). For each woman with CIS, 5 women in the control group were matched by date of first registered smear and age. Eligible women in the control group were randomly selected from each set of 5 women (n=604; 1754 smears); they had no history of CIS or invasive cervical carcinoma or hysterectomy before the date of diagnosis for the corresponding woman in the case group.

Assessment of risk factors

All smears taken after entry were analysed for HPV-16 by using quantitative polymerase chain reaction (5′-exonuclease [Taqman] method). The technician who analysed the smears was blinded to case control status. The level of β actin was also assessed.

Main outcome measure

Women with CIS were identified by the National Cancer Registry, and their histological samples were reassessed to confirm …

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  • Sources of funding: National Institutes of Health; Swedish Cancer Society; Danish National Research Foundation.

  • For correspondence: Dr N Ylitalo, Department of Medical Epidemiology, Karolinska Institute, Box 281, SE-171 77 Stockholm, Sweden. Fax +46 8 8 31 49 57.