This evaluation was informed by comprehensive and detailed use of epidemiological and cost data from the NHS Cervical Cancer Screening Programme Sentinel Sites Study and other observational studies, plus data from the screening programme in England. We found that the early use of human papillomavirus testing after treatment averts more cases of CIN3+ and is also cost saving compared with cytology only follow-up, because it seems to be more effective at the early identification of women who are at risk of recurrent disease in the future. The findings also indicate that the capacity of annual cytology to prevent CIN3+ in women previously treated for CIN depends on a very high level of compliance with annual visits. This is likely to explain, in part, the difference between our findings and those of a previous evaluation, which assumed perfect compliance with follow-up recommendations.5
We also found that human papillomavirus testing according to the sentinel sites protocol results in fewer colposcopies over 10 years than does cytology only follow-up, and a higher proportion of colposcopies resulted in re-treatment. This is potentially an important reduction in the burden of follow-up on women, as well as on the health system. It also indicates that the colposcopies done under this strategy are better targeted at women who will benefit from them. As a result of the successful implementation of the sentinel sites and this cost effectiveness analysis, the human papillomavirus test of cure is now being implemented nationally in England, so the cytology only protocol is no longer current practice.
When we assessed the relative effects and costs of alternative human papillomavirus based strategies, we found that once-only cytology and human papillomavirus testing at six months after treatment is predicted to have comparable effectiveness to a strategy involving three rounds of repeat testing; in addition, the once-only cytology and human papillomavirus based testing strategy was found to be less costly. This finding may be relevant to other settings, especially in countries that have implemented extended human papillomavirus testing protocols. For example, the national screening programmes in Australia and New Zealand have introduced recommendations involving repeated rounds of human papillomavirus and cytology testing after treatment, in which women are required to have negative results in both tests for two consecutive years before they are discharged back to routine screening.24
These recommendations were originally based, in part, on cost minimisation (rather than cost effectiveness) analysis comparing extended human papillomavirus testing with previous recommendations in those settings, which was annual cytological follow-up until the age of 70. To our knowledge, the comparative cost effectiveness of simplified human papillomavirus test based strategies compared with extended test protocols has not been examined in these settings and is a potential subject for future cost effectiveness analyses.
Follow-up testing at six months post-treatment could also be further streamlined to involve only human papillomavirus testing without cytology. Studies of longitudinal outcomes after primary human papillomavirus testing in the general population show that cumulative rates of CIN3+ in human papillomavirus negative women are very similar to rates in the group of women who are both human papillomavirus and cytology negative over several years of follow-up,26
implying that adjunctive testing with both tests is relatively inefficient compared with using human papillomavirus testing alone. However, further data on the comparative performance of human papillomavirus testing alone versus combined with cytological screening are needed in the post-treatment setting. We were not able to evaluate human papillomavirus testing as a standalone test in this evaluation, because the data used came from studies in which human papillomavirus testing was done at six months only when cytology was negative.
The high negative predictive value of post-treatment management involving human papillomavirus testing and cytology at six, 12, and 24 months has recently been reported to be maintained over five years.27
Longer term follow-up data from the Sentinel Sites Study will further enable the validity of the observable model predictions (such as rates of colposcopy and re-treatments) to be assessed. Our evaluation of the cost effectiveness of human papillomavirus as a test of cure over a period of 10 years represents a modelled extrapolation of data obtained from studies with shorter follow-up periods. Therefore, although our findings support the implementation of human papillomavirus based strategies for post-treatment management, a need remains for ongoing monitoring and evaluation of the long term safety of these strategies.
We found that the human papillomavirus test of cure according to the sentinel sites protocol is a more effective and less costly strategy than annual cytological follow-up over 10 years. The findings of this analysis suggest that a single round of cytology and human papillomavirus testing six months after treatment effectively identifies women at future risk of serious recurrent cervical disease. The results support the full scale implementation within the NHS Cervical Cancer Screening Programme of human papillomavirus testing as a test of cure after treatment for CIN.
What is already known on this topic
- Results of previous studies are inconsistent about whether human papillomavirus (HPV) testing as a test of cure after treatment for cervical intraepithelial neoplasia (CIN) is cost effective
What this study adds
- If realistic assumptions are made about women’s compliance with follow-up recommendations, HPV testing is likely to be more effective and cost less than strategies based on annual cytological follow-up of women treated for CIN