The renewal of the National Cervical Screening Program

I question that clinicians and the public may be reassured that the evidence underpinning the renewal of the National Cervical Screening Program (NCSP) is sound.1 A fundamental aspect of the sensitivity of a screening test is the definition of the disease of interest that the test seeks to detect. For cancer screening, it is disease that will progress to life-threatening cancer and not the sensitivity to detect disease that only may progress to cancer.2,3 It is a very common but profound error to consider these equivalent,2 particularly when comparing two tests that measure different aspects of the disease process. Overdiagnosis and regression biases are avoided by using the interval cancer method to estimate sensitivity.2,3

The estimates of the sensitivity of human papillomavirus (HPV) testing and cytology, used in the models of the New South Wales group to justify the NCSP renewal policy, were for the detection of cervical intraepithelial neoplasia (CIN) grade 2+ and not for the detection of progressing disease.4 Their approach is fraught because CIN 2 and CIN 3 have different rates of regression and persistence. A higher sensitivity of HPV to detect CIN 2, but lower sensitivity to detect CIN 3 or progressive disease, will produce a lower effectiveness to reduce invasive cervical cancer than cytology, despite a higher sensitivity to detect CIN 2+. There is evidence from the randomised controlled trials that this is the case, even within the regression, persistence but no progression, and progression spectrum of CIN 3.

The results of the only randomised trial of the implementation of HPV testing in a screening program, published in 2013,2 found the sensitivity of HPV testing (87%) to detect disease that progresses to invasive cervical cancer to be lower than cytology screening (93%). The authors concluded that “sensitivity of HPV testing was similar to that of Pap testing but caused more overdiagnosis. Therefore, implementation of HPV testing needs to be reconsidered especially in countries with well organised programmes”. This suggests that it is mathematically impossible for HPV testing to provide greater protection from invasive cervical cancer than cytology. Assuming participation of 80%, the renewal program will increase the incidence of cervical cancer by about 39%, and the unit of economic effectiveness will be dollars saved per life prematurely lost. From the perspective of public health medicine, it would be professionally negligent not to estimate the effect of moving to 5-yearly HPV testing using the Finnish estimates of the sensitivity of HPV testing and cytology, but instead rely only on estimates with major regression and overdiagnosis bias.4