A prospective study showing long-term infection with human papillomavirus 16 before the development of cervical carcinoma in Situ

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  • Nathalie Ylitalo
  • Agnetha Josefsson
  • Mads Melbye
  • Per Sorensen
  • Morten Frisch
  • Andersen, Per Kragh
  • Pär Sparen
  • Margit Gustafsson
  • Patrik Magnusson
  • Jan Ponten
  • Ulf Gyllensten
  • Hans Olov Adami

Human papillomavirus 16 (HPV16) is a predominant cause of cervical neoplasia. However, no population-based study with long-term follow-up has clarified the temporal relationship between HPV16 infection and occurrence of carcinoma in situ, or the importance of recurrent or persistent infection. This nested case-control study was carried out in a population-based cohort of women participating in cytological screening whose initial smear, taken in 1969-1995, was normal. During up to 26 years of follow-up, carcinoma in situ was diagnosed in 484 eligible women. Archival smears from these women were compared with smears from 619 individually matched controls. After DNA extraction, a highly sensitive PCR system was used to detect HPV16. Among case women, the prevalence of HPV16 positivity was 56% at the time of diagnosis. The relative risk of cervical carcinoma in situ increased from 3.6 (95% confidence interval, 1.2-11.0) 13 years before diagnosis to 11.1 (95% confidence interval, 5.5-22.2) 1 year before diagnosis. Having a positive smear at entry to the cohort increased risk >5-fold, whereas having persistent infection with HPV in two subsequent smears increased risk 30-fold. We estimated that among HPV16-positive women, the median incubation period from infection to carcinoma in situ was 7-12 years. We conclude that evidence of persistent and/or recurrent infection is associated with a drastically higher risk of cervical carcinoma in situ than occasional infection with HPV16.

Original languageEnglish
JournalCancer Research
Issue number21
Pages (from-to)6027-6032
Number of pages6
Publication statusPublished - 1 Nov 2000

ID: 259465102