| Popis: |
The work presented in this thesis was performed to investigate the role of human papillomavirus (HPV) testing for improved detection of cervical neoplasia in the Scottish Screening Programme (CSP). A longitudinal study of 975 archived cervical smears from women who had histologically-confirmed cervical intraepithelial neoplasia (CIN) showed that HPV positivity using Hybrid Capture Assay II (HCAII) was found to increase with increased cytological abnormality and 18% overall contained high-risk HPV (HR-HPV) DNA. Retrospective analysis of cytology data showed that the positive predictive value (PPV) of cytology alone for the detection of significant cervical disease was 71% while that of HPV testing alone was 38%. Combined cytology and HPV testing before biopsy would have increased the PPV to 78%. However, the negative predictive value (NPV) of a negative HR-HPV result with normal cytology was 100%. These results suggested that HPV testing may have a greater role in the exclusion of severe cervical diseases rather than as a predictor of its presence. In a split-sample study, comparing conventional Pan smears and liquid-based cytology (LBC), monolayer preparations from LBC samples reduced the inadequacy rate from 7.3% to 2%. LBC also reduced the number of borderline smear reports from 7.9% to 4.2% and increased the number of severe cytological abnormalities detected. The clinical value of LBC was further endorsed in the direct-to-vial study where LBC replaced conventional smears within the cervical screening programme. Monolayer preparations from over 4700 LBC samples showed a reduction in the inadequacy rate from around 10% to less than 1%. This reduced the level of anxiety in women and provided savings in repeat clinic visits for patients, repeat samples for laboratories and administrative time at both sites. HPV testing would be a useful adjunct to cytology for improved management of women with borderline smear results. In the split sample study, 44.3% of women with a previous borderline or low-grade cervical abnormality were HR-HPV DNA positive. However, if all 110 HPV negative women had been managed by routine recall than only two cases of CIN1 would have been missed while 160 repeat visits and smears would have been saved. This clearly has benefits for both patients and clinicians at the primary care level and HPV-based triage has the potential to significantly reduce referrals to colposcopy. |
