Primary HPV DNA screening with cytology triage is more sensitive than conventional screening. Among women aged 35 years or older, primary HPV DNA screening with cytology triage is also more specific than conventional screening and decreases colposcopy referrals and follow-up tests.

Objective To assess the performance and impact of primary human papillomavirus (HPV) DNA screening with cytology triage compared with conventional cytology on cervical cancer and severe pre-cancerous lesions. Design Randomised trial. Setting Population based screening programme for cervical cancer in southern Finland in 2003-5. Participants 58 076 women, aged 30-60, invited to the routine population based screening programme for cervical cancer. Interventions Primary HPV DNA test (hybrid capture II) with cytology triage if the result was positive or conventional cytological screening (reference). Main outcome measures Rate of cervical cancer, cervical intraepithelial neoplasia (CIN) grade III, and adenocarcinoma in situ (as a composite outcome referred to as CIN III+) during 2003-7 through record linkage between files from the screening registry and the national cancer registry. Results In the HPV and conventional arms there were 95 600 and 95 700 woman years of follow-up and 76 and 53 cases of CIN III+, respectively (of which six and eight were cervical cancers). The relative rate of CIN III+ in the HPV arm versus the conventional arm was 1.44 (95% confidence interval 1.01 to 2.05) among all women invited for screening and 1.77 (1.16 to 2.74) among those who attended. Among women with a normal or negative test result, the relative rate of subsequent CIN III+ was 0.28 (0.04 to 1.17). The rate of cervical cancer between arms was 0.75 (0.25 to 2.16) among women invited for screening and 1.98 (0.52 to 9.38) among those who attended. Conclusions When incorporated into a well established organised screening programme, primary HPV screening with cytology triage was more sensitive than conventional cytology in detecting CIN III+ lesions. The number of cases of cervical cancer was small, but considering the high probability of progression of CIN III the findings are of importance regarding cancer prevention.Trial registration Current Controlled Trials ISRCTN23885553.

The role of high-risk human papillomavirus (hrHPV) testing in primary cervical screening has not been established. We generated a randomised evaluation design ultimately to clarify whether primary hrHPV testing implemented into routine screening can bring increase in the programme effectiveness. The aim of the present report on first-year results was to assess the cross-sectional relative validity parameters for routine hrHPV screening, in comparison with conventional screening. An equal number of women invited to routine screening was randomly allocated to primary hrHPV screening (n ¼ 7060) and to cytological screening (n ¼ 7089). In the hrHPV screening arm, after a single positive hrHPV test result, the need of colposcopy referral was determined by a cytological triage test. Compared with the conventional arm, more colposcopy referrals were made in the hrHPV screening arm (relative risk 1.51, confidence interval 95% 1.03 -2.22). Specificity of the primary screening with sole hrHPV test (91.5 -92.1%) was much lower than that with the cytology triage (98.7 -99.3%), which was not quite as specific as screening with conventional cytology (99.2 -99.6%). Compared with conventional cytology, primary screening with hrHPV test results in increased cross-sectional relative sensitivity at the level of all positive lesions at the cost of substantial loss in specificity. With cytology triage, the specificity improves to the level of conventional cytology.

We compared test sensitivity (in terms of prevented cancers) and overdiagnosis (in terms of non-progressive pre-invasive lesions) between the human papillomavirus test (HPV test, Hybrid Capture 2) and the traditional Pap test in routine screening for cervical cancer. The design was a randomised (1:1) health services study in Finland with intake between 2003 and 2007. We estimated sensitivity by the incidence method within one screening round. Overdiagnosis was based on the rate of cervical intraepithelial Grade 3 (CIN3) lesions diagnosed at screen and during the following interval. Out of 203,788 randomised women 132,298 attended (65% in both study arms) and 600,753 person-years accumulated among attenders up to the end of 2010. In all attenders, 34 invasive cervical cancers and 288 CIN3 lesions were diagnosed at screen or during the following interval. The interval cancer incidence was 2.5/10 5 person-years (sensitivity 0.87) and 1.4 (sensitivity 0.93) in the HPV arm and Pap test arm, respectively. The rate of CIN3 lesions was 57.1 and 38.8, respectively. In conclusion, 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.Recommendations concerning new screening tests for cervical cancer are mostly based on cross-sectional studies and on detection rates of pre-invasive lesions. 1-5 The few follow-up studies have focused on pre-invasive lesions and on the length of reassurance that a negative test provides. 6-10 Only few studies have had emphasis on public health aspects. 11,12 The purpose of screening is to prevent invasive cervical cancer and the demonstration of this effect requires follow-up for incident invasive cancers after the screen. In fact, detection (at screen) of pre-invasive lesions results in both benefit and harm; benefit through preventing some of the lesions from progressing to invasive cancer, and harm by detecting also such pre-invasive lesions that would never have progressed to invasive cancers. These two types of pre-invasive lesions cannot be separated and thus, both types have to be treated if diagnosed.Sensitivity measures a screening test's ability to correctly identify unrecognised disease. It can be estimated in several ways. The most common way is called the detection method 4 which is based on screen detected lesions, both pre-invasive and invasive ones. However, the sensitivity estimate is usually biased and too big (closer to one) due to overdiagnosis of the detection of pre-invasive lesions. Sensitivity can also be estimated by the incidence method 13 that is based on failures of screening.The purpose of the present study was to compare the human papillomavirus (HPV) test to the traditional Pap test in cervical cancer screening in terms of sensitivity (detection of progressive lesions) and overdiagnosis (detection of nonprogressive lesions). Material and methodsIn Finland, women between 30 and 60 years of age (sometimes ...

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