Risk reduction by HPV-Testing in Women with Premalignant Cervical Lesions: Studies of clinical management and observations on the immunological background

Chapters 2.1, 2.2 and 4 are preprints of articles accepted for publication in the International Journal of Cancer, Wiley Inc.

Development of cervical cancer is preceded by well-defined premalignant lesions. These lesions are classified as cervical intraepithelial neoplasia (CIN) and are detectable by cervical cytology, resulting in nationwide cervical cancer screening programs. Although these programs have led to a substantial reduction in mortality and morbidity of cervical cancer, there are many drawbacks including limited accuracy of cytology, unnecessary screening rounds, and over-treatment. A persistent infection with high risk Human Papillomavirus (hrHPV) is necessary for development, maintenance and progression of CIN lesions. HPV testing, as an adjunct to cytology, can lead to a better selection of women at risk for development of cervical cancer and consequently to more efficient cervical cancer screening strategies. The use of HPV testing can reduce the risk of detection failure in cervical screening, the studies described in this thesis confirm this in clinically validated settings. New guidelines and recommendations are formulated.