Greater sensitivity, which lowers cancer incidence (Rocco et al. Lancet 2014), extended screening intervals and prophylactic vaccination provide the rationale for high-risk human papillo-mavirus (HR-HPV) testing to replace cytology as the primary test in cervical screening programmes both in the UK and internationally. Zorzi et al. report in BJOG, a timely cohort study from Italy of primary HPV cervical screening, concluding that following primary HPV screening, 3 years is too soon for a repeat screening round. Trials of HR-HPV testing have already demonstrated that the screening interval can safely be extended beyond 3 years (Kitchener et al. Eur J Cancer 2011;47:864-87), but 'real world' data are nonetheless relevant. The group of greatest interest is HR-HPV-positive women with negative cytology, which warrants early recall at 12 months to realise the added sensitivity of HPV screening. Clinical outcomes that matter most are: compliance with early recall, the positive predictive value (PPV) of additional colposcopy referral, the proportion of high-grade cervical intraepithelial neoplasia (CIN) detected at early recall, and the prevalence of HPV and high-grade CIN at the 3-year screening round, the latter serving as a surrogate of the safety of interval extension. These are all available from the Italian study, but two limitations, which affect the generalis-ability of the findings, should be noted. The first was the low prevalence of HR-HPV (6.3%), when compared with age-matched data of around twice that level in the ARTISTIC trial, which screened an urban UK population using the same assay(Kitchener et al. Br J Cancer 2006;95:56-61). This has a direct impact on both colposcopy referral and CIN detection. The second is that the use of a separate sample for conventional cytology, rather than reflex liquid-based cytology from the HPV sample, is suboptimal. Of those who screened as HPV-positive, 58% had negative cytology, which required 12 month recall. Encouragingly, over 80% attended early recall, of whom 42% had cleared HPV, the rest were referred to col-poscopy with detection of high-grade CIN in only 7.5%. These lesions amounted to an additional one-third over that found at initial screening, confirming inferior sensitivity of the baseline conventional cytology. At the 3-year round, the combined detection (baseline plus early recall) of high-grade CIN was only 0.1% of those screened (compared with 0.44% in the first round) and required almost 20 colposcopies for each high-grade CIN lesion, with just two CIN 3 lesions among 180 colposcopies, and over 21 000 women screened. This study certainly confirms the safety of extending the screening interval ; 5 years has already been determined for the Dutch and Australian programmes, and a similar interval will probably be used in the English Programme , with the potential for longer intervals in women over 50 years. The Italian study ignored partial genotyp-ing, as used in the ongoing English HPV pilot project, to detect HPV types 16/18 at early recall to achieve mo...

BackgroundEuropean guidelines for cervical cancer screening now recommend the use of clinically validated assays for high-risk HPV-DNA sequences as primary test in women older than 30 years, performed in centralized laboratories, and run on systems providing automated solutions for all steps.MethodsWe conducted a comparison study, according to the international guidelines, nested within the organized population-based cervical screening program, between the cobas 4800 and 6800 systems (Roche Diagnostics), to evaluate accuracy and reproducibility of HPV test results and laboratory workflow. In Italy implementation of HPV cervical screening is under way on a regional basis; in Veneto it started in June 2015, following a piloting phase; the assay in use in the three centralized laboratories is the cobas 4800 HPV test, run on the cobas 4800 system. Comparison of HPV results with a new version of the assay (cobas 6800/8800 HPV) run on the cobas 6800 system, and intra- and inter-reproducibility analyses have been conducted in samples collected in PreservCyt medium (Hologic) from women without and with a subsequent diagnosis of high-grade lesion.ResultsSamples from women older than 30 years attending organized cervical cancer screening were used. Clinical sensitivity and specificity were evaluated on 60 cases and 925 controls, respectively; intra-laboratory reproducibility and inter-laboratory agreement by the 6800 system were evaluated on 593 and 460 specimens, respectively. Our results showed a very high agreement (> 98%) for overall qualitative results between the two systems; clinical sensitivity and specificity of the HPV assay run on 6800 were non-inferior to those of the HPV assay run on 4800 (p = 0,0157 and p = 0,0056, respectively, at the recommended thresholds of 90 and 98%); kappa values of 0.967 and 0.969 were obtained for intra- and inter-laboratory reproducibility analyses in the 6800 system. The 6800 platform displayed several technological improvements over the 4800 system, with higher throughput and laboratory productivity, and lower operator’s hands-on time.ConclusionsThe new cobas 6800/8800 HPV assay run on the 6800 instrument is suitable for use in large centralized laboratories included within population-based cervical cancer screening programs.

Cervical cancer screening by human papillomavirus (HPV) DNA testing with cytology triage is more effective than cytology testing. Compared to cytology, the HPV DNA test's higher sensitivity, which allows better protection with longer intervals, makes it necessary to triage the women with a positive result to compensate its lower specificity. We are conducting a large randomized clinical trial (New Technologies for Cervical Cancer 2 [NTCC2]) within organized population-based screening programs in Italy using HPV DNA as the primary screening test to evaluate, by the Aptima HPV assay (Hologic), the use of HPV E6-E7 mRNA in a triage test in comparison to cytology. By the end of June 2016, data were available for 35,877 of 38,535 enrolled women, 2,651 (7.4%) of whom were HPV DNA positive. Among the samples obtained, 2,453 samples were tested also by Aptima, and 1,649 (67.2%) gave a positive result. The proportion of mRNA positivity was slightly higher among samples tested for HPV DNA by the Cobas 4800 HPV assay (Roche) than by the Hybrid Capture 2 (HC2) assay (Qiagen). In our setting, the observed E6-E7 mRNA positivity rate, if used as a triage test, would bring a rate of immediate referral to colposcopy of about 4 to 5%. This value is higher than that observed with cytology triage for both immediate and delayed referrals to colposcopy. By showing only a very high sensitivity and thus allowing a longer interval for HPV DNA-positive/HPV mRNA-negative women, a triage by this test might be more efficient than by cytology.