Although the molecular events involved in cervical HPV infection and the development of neoplasia are not completely understood, the clinical course of cervical carcinogenesis is now relatively well charted. Therefore, the natural history of cervical disease lends itself to a modelling approach. Modelling can assist with decision making by exploring the implications of a range of possible interventions (Royston, 1999
) and has been previously used to evaluate the natural history of CIN (Myers et al, 2000
) and changes in screening practice (Sherlaw-Johnson et al, 1994
). The model we have described builds on previous work to provide a tool that encompasses the current understanding of the natural history of cervical neoplasia and is specific to the UK setting.
We used the Markov simulation of the events leading to cervical cancer and the screening and treatment of cervical disease to predict cancer incidence rates in the UK population under various conditions. The predicted age-specific cervical cancer incidence in the absence of screening was 18.6 per 100
000 women, standardised to the European standard population. The cancer registration data, standardised to the same population, suggest rates between 14 and 16 per 100
000 during the 1970s and 1980s in England (Quinn et al, 1999
). Some opportunistic cervical screening was performed in the UK from the 1960s and, as expected, the observed incidence in the context of opportunistic screening was slightly less than the model prediction for a completely unscreened population. Since cancer registration data for England, which has only been collected since the early 1970s, incorporates a screening effect, they cannot be used to validate the model prediction for the incidence of cervical cancer in the UK population in the absence of screening. There are additional problems associated with using historical data, in terms of disentangling the influence of cohort effects related to differential HPV exposure and the influence of changing practice in screening, diagnostic and treatment procedures. For these reasons, we thought it most appropriate to estimate the validity of the model by incorporating the effect of pre-2003 screening practice and comparing the model predictions of cervical cancer incidence rates with recent cancer registration data for the UK. We found close agreement between the observed and predicted values of age-specific cervical cancer incidence, cumulative lifetime incidence and age-standardised incidence in the screened UK population ().
The primary objective of the study was to assess the likely long-term impact of the 2003 NHSCSP recommended changes in screening intervals. Although the current study has focused upon screening in the UK, a Working Group of the International Agency for Research on Cancer (IARC) has recently confirmed the efficacy of screening every 3 years between the ages of 25 and 49 years and every 5 years between the ages of 50 and 64 years (International Agency for Research on Cancer, 2004
), and therefore our results also have more general implications. We found that ceasing screening in women under the age of 25 years will have a very small effect on the lifetime incidence of cervical cancer. Reducing the screening interval to 3 years in women aged 25–49 will have major benefits, resulting in an 18% reduction of the cumulative lifetime incidence of cervical cancer, compared to pre-2003 screening. As a result, the predicted proportion of cervical cancers prevented in women aged 20–79, compared to an unscreened population, is 63%. Our findings of a reduction in cervical cancer incidence broadly agree with the original estimates performed by Sasieni et al (2003)
, who found that the new screening intervals would be associated with a 61% reduction in women aged 20–39 years and an 84% reduction in women aged 40–54 years, compared to women who were never screened. However, the results are not directly comparable because our model included microinvasive cancers, whereas their estimate was based on 1305 women aged 20–69 years with Stage 1B+ cancer and 2532 age-matched control women, but did not include 537 microinvasive (Stage 1A) cancers and 490 cancers of unknown stage observed in women of the same age group. Also, Sasieni et al
assumed that all women with abnormal smears are prevented from developing cancer, which is not assumed in our model. They calculated the relative risks resulting from 3- or 5-year screening intervals in various age groups as a function of the time since the last negative smear, and then derived a summary measure of the overall proportion of cancers preventable, using a previously described method (Sasieni et al, 1996
). This approach provided a measure of the efficacy of screening in individuals who complied with screening recommendations. Our study extends these results by assessing the overall effectiveness of the proposed NHSCSP changes across the lifetime of a cohort of women, taking into account real-world limitations in population screening coverage rates, the sensitivity of screening and the efficacy of treatment. For women over 50 years of age, the modelling approach takes into account the carried-over beneficial effect resulting from previous 3-yearly screening of the cohort when they were aged 25–49 years, whereas this carry-over effect could not be taken into account in the relative risk estimates performed by Sasieni et al
Some further reductions in cervical cancer incidence could be achieved after the implementation of the 2003 screening interval recommendations, by means of increasing the sensitivity of the screening test or extending screening to older women. Increasing the sensitivity of the screening test would result in a substantial further reduction of the cumulative lifetime incidence of cervical cancer, of up to 27%. Alternatively, when we examined the possibility of extending screening to include 5-yearly coverage of women aged 65–79 years, we found that there was an 11% further reduction in cumulative lifetime incidence predicted. However, this measure does not take into account the person-years saved, and reducing incidence in women over 65 years of age is expected to save fewer years of life compared to reducing incidence in younger women. Therefore, when comparing the two possible strategies, both the relative magnitudes of the expected improvements and the age ranges over which incidence is reduced would suggest that increasing screening sensitivity would be the most preferable option for the future. However, cost-effectiveness analysis is required to fully assess the public health impact of such future screening strategies.
In conclusion, a UK-specific Markov model for cervical HPV infection, CIN and invasive cervical cancer has been constructed, successfully validated against cancer registration data and used as a tool to evaluate the impact of screening policy changes. The results support the 2003 NHSCSP recommendations that screening should start at age 25 years, that screening intervals should be reduced to 3 years in women aged 25–49 years and that screening intervals should be standardised to 5 years in those aged 50–64, and suggest that a substantial further reduction in cervical cancer incidence should follow.