Viral load of human papilloma virus 16 as a determinant for development of cervical carcinoma in situ: a nested case-control study.

Infection with certain types of human papillomavirus (HPV), which is common among young women, increases the risk of cervical cancer. However, less than 1% of young women positive for oncogenic types of HPV develop cervical cancer. We investigated whether the amount of HPV DNA is a useful predictor of progression to cervical carcinoma in situ. We estimated the amount of HPV 16 DNA by a PCR that uses the 5'-exonuclease (Taqman) method, in 478 women with cervical carcinoma in situ and 608 individually matched controls. To adjust for differences in the amount of genomic DNA between samples, we estimated the amount of a nuclear gene (beta-actin). We studied multiple smears (total 3835 archived samples) from each woman, taken over periods of up to 26 years, that covered normal cytology to development of cervical cancer. The risk of cervical carcinoma in situ increased with the amount of HPV 16 DNA. Analysis of the first smear from each woman, collected a mean of 7.8 years before cancer diagnosis, showed that women with the 20% highest amount of HPV 16 DNA were at a 60-fold higher risk of developing cervical carcinoma in situ than women negative for HPV 16. The first smear samples were classified as normal by squamous-cell cytology. Analysis of the amount of HPV DNA can predict cancer risk at a stage when current screening methods are uninformative. Testing for the amount of HPV 16 DNA during gynaecological health checks might strikingly improve our ability to distinguish between infections that have a high or low risk of progressing into cervical cancer.