AbstractsBiology & Animal Science

Effective primary and secondary prevention tools exist for cervical cancer in the form of human papillomavirus (HPV) vaccines and cervical screening. In order to maximize the impact of prevention strategies in Sweden and European countries, this thesis sought to investigate the long-term effectiveness of different screening strategies and the long-term risk associated with HPV infections, the organization and quality of existing screening programs, and the effectiveness of alternative vaccination strategies. HPV-based screening has been evaluated using intermediate outcomes while its effectiveness against cancer had not been fully examined. In Study I, the European randomized controlled trials (RCT) of screening methods were pooled to investigate the relative efficacy of HPV-based versus cytology-based screening for the prevention of invasive cervical cancer. We found that HPV-based screening provides 60-70% greater protection against invasive cervical cancer compared to cytology-based screening. To address the issue of determining intervals for HPV-based screening and to investigate concerns regarding overdiagnosis with HPV-based screening, a long-term follow-up of the Swedescreen RCT was completed in Study II. The longitudinal performance of cytology- and HPV-based screening was explored and the sensitivity for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) of HPV testing at 5 years of follow-up was similar to that of cytology testing at 3 years. Over 13 years of follow-up, we found that the increased sensitivity of HPV screening for CIN2+ reflects earlier diagnosis rather than overdiagnosis and low long-term risks among HPV negative women suggest that extending screening intervals with HPV-based screening would be possible. The incidence of low-grade cervical lesions is increasing in Sweden. Low-grade lesions require follow-up, creating a burden to the woman and the healthcare system. Examining the long-term HPV-type-specific risk for atypical squamous cells of undetermined significance (ASCUS), low grade squamous intraepithelial lesions (LSIL) and cervical intraepithelial neoplasia grade 1 (CIN1) is of interest to inform screening and vaccination programs. In Study III, we investigated the long-term type-specific absolute risk, population attributable proportion, and incidence rate ratios for ASCUS/LSIL by HPV type. The type-specific IRRs for ASCUS/LSIL were high in the first screening round but decreased over subsequent screening rounds. Type 16 contributed to the greatest proportion of low-grade lesions in the population followed by type 31. Most lesions were caused by new infections and found in the first screening round. Organized, population-based screening with quality assurance (QA) at all levels is recommended by the European Commission to ensure equity and cost-effectiveness of programs. Significant differences in cervical cancer incidence and mortality exist between European countries. In Study IV, a comprehensive questionnaire was developed and circulated among EU/EFTA…