Development of a pre-malignant condition of the cervix.

Cancer Res. 2000 Nov 1;60(21):6027-32.

A prospective study showing long-term infection with human papillomavirus 16 before the development of cervical carcinoma in situ.Ylitalo N,Josefsson A,Melbye M,Sorensen P,Frisch M,Andersen PK,Sparen P,Gustafsson M,Magnusson P, Ponten J,Gyllensten U,Adami HO.

Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden. Nathalie.Ylitalo@mep.ki.se 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.

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