Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screening: a prospective study

Background A relation has been established between infection with high-risk types of human papillomavirus and development of cervical cancer. We inves tigated a role for testing for human papillomavirus as part of cervical-can cer screening. Methods We monitored by cytology, colposcopy, and testing for high-risk hum an papillomavirus 353 women referred to gynaecologists with mild to moderat e and severe dyskaryosis. The median follow-up time was 33 months. At the l ast visit we took biopsy samples. Our primary endpoint was clinical progres sion, defined as cervical intraepithelial neoplasia (CIN) 3, covering three or more cervical quadrants on colposcopy, or a cervical-smear result of su spected cervical cancer. Findings 33 women reached clinical progression. All had persistent infectio n with high-risk human papillomavirus. The cumulative 6-year incidence of c linical progression among these women was 40% (95% CI 21-59). in women with end histology CIN 3, 98 (95%) of 103 had persistent infection with high-ri sk human papillomavirus from baseline. Among women with mild to moderate dy skaryosis at baseline, a second test for human papillomavirus at 6 months p redicted end histology CIN 3 better than a second cervical smear. Interpretation Persistent infection with high-risk human papillomavirus is necessary for development and maintenance of CIN 3. All women with severe d yskaryosis should be referred to gynaecologists, whereas women with mild to moderate dyskaryosis should be referred only after a second positive test for high-risk human papillomavirus at 6 months.