High-risk human papillomavirus (hrHPV) testing has a higher sensitivity but lower specificity than cytology for detection of high-grade intraepithelial neoplasia (CIN). To avoid over-referral to colposcopy and overtreatment, hrHPV-positive women require triage testing and/or followup. A total of 25,658 women (30-60 years) enrolled in a population-based cohort study had an adequate baseline Pap smear and hrHPV test. The end-point was cumulative two-year risk of CIN grade 3 or worse (CIN31). In a post-hoc analysis, fourteen triage/followup strategies for hrHPV-positive women (n 5 1,303) were evaluated for colposcopy referral rate, positive (PPV) and negative predictive value (NPV). Five strategies involved triage testing without a repeat test and nine strategies involved triage testing followed by one repeat testing. The tests were cytology, hrHPV, HPV16/ 18 genotyping and HPV16/18/31/33/45 genotyping. Results were adjusted for women in the cohort study who did not attend repeat testing. Of the strategies without repeat testing, combined cytology and HPV16/18/31/33/45 genotyping gave the highest NPV of 98.9% (95%CI 97.6-99.5%). The corresponding colposcopy referral rate was 58.1% (95%CI 55.4-60.8%). Eight of the nine strategies with retesting had an estimated NPV of at least 98%. Of those, cytology triage followed by cytology at 12 months had a markedly lower colposcopy referral rate of 33.4% (95%CI 30.2-36.7%) than the other strategies. The NPV of the latter strategy was 99.3% (95%CI 98.1-99.8%). Triage hrHPV-positive women with cytology, followed by repeat cytology testing yielded a high NPV and modest colposcopy referral rate and appear to be the most feasible management strategy.Strong evidence is now available that testing for high-risk human papillomavirus (hrHPV) infection is more sensitive than cytology in detecting high-grade cervical intraepithelial neoplasia (CIN). 1-7 However, hrHPV testing also detects more transient hrHPV infections than cytology, 1,8 which may lead to over-referral for colposcopy and thus overtreatment. 5 Management of hrHPV-positive women is, therefore, of major concern. In particular, in countries with an efficient cytology-based screening program and a moderate colposcopy referral rate such as The Netherlands and the United Kingdom, the increased burden on healthcare resources upon introduction of a less-specific screening test may be Key words: human papillomavirus, uterine cervical neoplasms, cervical intraepithelial neoplasia, colposcopy, early detection of cancer CJLM was the project leader, designed the study with SB, LR and PJFS and had access to all data. DCR, together with JB, CJLM, FJvK, VC and PJFS, drafted the manuscript. DCR, JB and VC were responsible for data analysis. ATH, DAMH CJLM and PJFS were responsible for HPV testing and HPV genotyping. LR was responsible for database management. DCR and WMV were responsible for the logistics. RHMV was responsible for communication with gynaecologists. FJvK and LR were responsible for cytology testing. All authors critically...

Background:Human papillomavirus (HPV) testing is more sensitive than cytology for detecting high-grade cervical intraepithelial neoplasia (CIN). We evaluated the performance of high-risk HPV (hrHPV) testing in routine screening.Methods:In all, 25 871 women (29–61) enrolled in our population-based cohort study were offered both cytology and hrHPV testing. High-risk HPV-positive women with normal cytology and an age-matched subcohort of hrHPV-negative women with normal cytology were invited for repeat testing after 1 and/or 2 years and were referred for colposcopy if they presented with abnormal cytology and/or a positive hrHPV test. The hrHPV-positive women with borderline or mild dyskaryosis (BMD) and all women with moderate dyskaryosis or worse (>BMD) were directly referred for colposcopy. Women with BMD and an hrHPV-negative test were advised to repeat cytology at 6 and 18 months and were referred for colposcopy if the repeat cytology test was abnormal. The main outcome measure was CIN grade 3 or worse (CIN3+). Results were adjusted for non-attendance at repeat testing.Results:The hrHPV-positive women with abnormal cytology had a CIN3+ risk of 42.2% (95% confidence interval (CI): 36.4–48.2), whereas the hrHPV-positive women with normal cytology had a much lower risk of 5.22% (95% CI: 3.72–7.91). In hrHPV-positive women with normal cytology, an additional cytology step after 1 year reduced the CIN3+ risk to only 1.6% (95% CI: 0.6–4.9) if the repeat test was normal. The CIN3+ risk in women with hrHPV-positive normal cytology was higher among women invited for the first time (29–33 years of age) (9.1% 95% CI: 5.6–14.3) than among older women (3.0% 95% CI: 1.5–5.5).Conclusion:Primary hrHPV screening with cytology triage in women aged ⩾30 years is an effective way to stratify women on CIN3+ risk and seems a feasible alternative to cytological screening. Repeat cytology after 1 year for hrHPV-positive women with normal cytology is however necessary before returning women to routine screening.

Aims: To compare the ability of different B-type natriuretic peptide (BNP) assays to identify heart failure in stable elderly patients with a diagnosis of chronic obstructive pulmonary disease (COPD). Methods: 200 patients aged ≥65 years with COPD according to their general practitioner and without known heart failure, underwent a diagnostic work-up. The final diagnosis of heart failure was established by a panel using the diagnostic principles of the European Society of Cardiology. All available diagnostic results, including echocardiography, but not BNP or NT-proBNP measurements, were used. The ability of different B-type natriuretic peptide assays to identify heart failure was estimated using the area under the receiver operating characteristic curves (ROC-area). Results: The ROC-areas did not differ significantly between the various assays of NT-proBNP and BNP, and ranged from 0.68 (95%CI 0.60-0.73) to 0.73 (95%CI 0.64-0.81). For NT-proBNP the age-and gender-independent 'optimal' cut-point was 15 pmol/l (125 pg/ml) and for BNP 10 pmol/l (35 pg/ml). All assays were much better at excluding than detecting heart failure. Conclusions: All assays of B-type natriuretic peptide showed reasonable and comparable accuracy in recognising heart failure. At 'optimal' cut-points, all assays performed better at excluding than detecting new cases of heart failure in this population.

In practice, a valid diagnosis in patients suspected of slow-onset heart failure remains elusive for many in the absence of echocardiographic imaging.

We studied the effectiveness of high-risk human papillomavirus (hrHPV) triage for immediate colposcopy in women with borderline or mild dyskaryosis (BMD). In the Utrecht province of the Netherlands, women aged 30-60 years who participated in the regular cervical screening programme were offered hrHPV testing and cytology (intervention group) or cytology only (control group). In the intervention group (n 5 337), women with BMD were immediately referred for colposcopy only if the sample was hrHPV positive. Women with a hrHPV negative test were advised to repeat cytology at 6 and 18 months and were referred for colposcopy if and when the repeat test result was positive (BMD or worse). In the control group (n 5 329), referral of women with BMD was delayed until cytology was repeatedly positive at 6 or 18 months. The CIN3 detection rates were 10.7% (36/337) in the intervention group and 6.4% (21/329) in the control group (p 5 0.047). Moreover, hrHPV triaging resulted in shorter time to diagnosis (154 vs. 381 days). Although the number of colposcopy referrals was 51.5% higher in the intervention group than in the control group, the medical costs per detected CIN3 were slightly lower ([euro] 4781 vs.[euro] 6235). If, in addition, hrHPV negative women had been referred back to routine screening at baseline, the CIN3 rate would have been 10.1% (34/337) and colposcopy rate would only have been 30.4% higher than in the control group. This study shows that hrHPV triaging of women with BMD is at least as effective for detecting CIN3 as repeat cytology, also when hrHPV negative women are referred back to routine screening.In many European population-based screening programmes, women with borderline or mild dyskaryosis (BMD) are recalled for repeat cytology before being referred for colposcopy only if the cytological abnormality persists. This policy is used because only 5-15% of these women have or will develop high-grade cervical lesions.1-3 A disadvantage of repeat testing is that women may become lost during follow-up. 4 Repeat cytology also induces a considerable amount of side effects in terms of psychological distress. 5,6 Several groups have studied the possible value of hrHPV testing and cytology for the detection of cervical lesions. 7,8 Most studies show that hrHPV testing is a sensitive instrument to triage women with BMD, but the optimal triaging strategy remains controversial. 9,10 In the Netherlands, women with BMD are followed with cytology testing at 6 and 18 months. Since 2006, screening laboratories may choose to include a hrHPV test in the repeat cytology at 6 months.11 This leads to a reduction in the number of repeat smears as it is considered safe to refer women with normal cytology and a negative hrHPV test back to the routine screening. A more substantial reduction in the number of repeat smears is expected when women with BMD are tested for hrHPV at baseline. However, population-based prospective evidence, in terms of the end-points CIN3 or cancer (CIN3þ), colposcopy referrals and medical costs needed...