Estimation of disease severity in the NHS cervical screening programme. Part II: quantitative methods of estimating disease severity and progression potential

Abstract

This is the second of a two-part paper exploring the use of a more quantitative approach to both cytology and histology disease severity measurements. In Part I the problem of artificial cut-off points was discussed and a semi-quantitative solution to the problem proposed. In Part II quantitative methods are proposed that are used to predict the estimated progression probability (EPP) to invasive cancer. Based on models derived from published data the grade number (GN) is related to the EPP to invasive cancer over the next 10 years for both cytology (CEPP) and histology (HEPP) using a look-up table. CEPP and HEPP are then adjusted by other factors such as age, persistence, HPV result, number of cells and lesion size to obtain the adjusted CEPP and HEPP (ACEPP and (AHEPP). The two factors can be combined to produce an adjusted weighted estimated progression potential using the formula AWEPP √((ACEPP + AHEPP)/2) × AHEPP) using a two to one bias in favour of the histology. As an example of the methodology consider a slide estimated as showing a 60% probability of moderate dyskaryosis (HSIL favouring CIN2) and 40% probability of mild dyskaryosis (LSIL favouring CIN1). The GN number would be 1.6 (as described in Part I) and the EPP over the next 10 years 0.78%. For a woman aged 52 years (correction factor ×2.0) with a second mildly dyskaryotic smear (correction factor ×1.25) and >50 dyskaryotic cells (correction factor 1.5) the ACEPP would be 0.78 × 2.00 × 1.25 × 1.5 = 2.9%. If the HEPP on histology was 50:50 between CIN1 and CIN2, the AHEPP can be calculated as 1.4%. The AWEPP would be √((2.9 + 1.4)/2 × 1.4) = 1.7%. The final estimate of disease progression potential based on both cytology and histology is 1.7% over 10 years. These quantitative approaches based on adjusted and weighted EPP provide a framework suitable for research, audit and comparison between screening centres, and for tailoring criteria for colposcopy referral and treatment. Further research is required to improve the estimates given in the paper.