Cervical screening with primary HPV : from research to clinical effectiveness

Sammanfattning: Organized cervical screening has greatly reduced the incidence of cervical cancer where implemented. Human papilloma virus (HPV) is the cause of cervical cancer, and in later years, convincing evidence has led to cervical screening with HPV as the primary method being implemented around the world. The overall aim of this thesis is to improve cervical screening, with focus on HPV screening.Papers I–III were performed with focus on postmenopausal women. Women aged, 55–59 years, excluded from the screening with a normal cytology cervical sample were found to have a high-risk HPV (hrHPV) prevalence of 5.5% in paper II. In a follow-up sample, 56% (71/126) had a persistent infection with the same genotype. Nineteen per cent of the women had dysplasia, where the majority of the high-grade squamous intraepithelial lesions (HSILs) were associated with HPV types other than HPV 16/18.Women 55-59 has a lower attendance rate in the study region, and since self-sample has been proven to increase attendance, paper I was performed to compare self-sample and professionally collected samples in these postmenopausal women. The concordance between the sampling methods was 83%, and both tests detected all histological HSILs. When including a study with older women (aged 70 years) in paper III, 23% of histological HSILs were found in hrHPV-positive women.Paper IV is a scientific evaluation of an implemented HPV-based screening programme, comparing clinical effectiveness and cost with cytology screening. More HSIL+ were detected in the new programme but at a higher cost than the old cytology-based programme. The screening visits for sampling accounted for two thirds of the costs.Altogether, the results indicate the importance of having a negative HPVtest before exiting screening. Data also present the necessity to find biomarkers that are more specific than cytology and HPV 16/18 for triaging women with hrHPV to further follow-up, both among postmenopausal women and other age groups when screening with HPV, since many women without HSIL are coming for clinical follow-up and treatment. Extending the screening interval between hrHPV-negative tests as well as implementing selfsampling to a greater extent can be important changes, since two thirds of the costs in the programme come from screening visits for sampling.