Use of a high-risk human papillomavirus DNA test as the primary test in a cervical cancer screening programme: a population-based cohort study.

OBJECTIVE: To present the results of the first 2 years of a human papillomavirus (HPV) test-based screening programme outside the research context. DESIGN: Population-based cohort study. SETTING: A cervical service screening programme in Italy. POPULATION: Women aged 25-64 years invited to screening from April 2009 to April 2011. METHODS: Eligible women were invited to undergo an HPV test: those with a negative HPV test went on to the next screening episode; those with a positive HPV went on to triage with a Pap smear. Women with positive cytology (i.e. positive for atypical squamous cells of undetermined significance or worse, ASC-US+) were referred to colposcopy, whereas those with negative cytology were referred to repeat HPV testing 1 year later. MAIN OUTCOME MEASURES: Participation rate, positivity at HPV and at triage, referral rate to colposcopy, positive predictive value for cervical intraepithelial neoplasia grade 2+ (CIN2+) at colposcopy, and detection rate for CIN2+. RESULTS: Participation increased compared with the previous Pap programme (60.6 versus 43.9%). The HPV positivity rate was 7.0; 39.6% of Pap smears were scored as positive, and therefore 2.8% of the women screened were referred for immediate colposcopy. The compliance of women who scored positive for HPV and negative for Pap for repeat HPV testing at 12 months was 78.6%, and the HPV positivity rate was 56.6%. The overall referral rate to colposcopy was 4.6%. The overall detection rate for CIN2+ was 4.5 versus 1.5% of the Pap programme (25-34 years, 8.2%; 35+ years, 3.6%). CONCLUSIONS: Compared with the traditional Pap test, the HPV programme recorded a higher response to invitation and an increased DR for CIN2+. The most critical aspects were the reading of cytology in women that were positive for HPV and the increased workload at colposcopy.

[Facilitation of the onset of tetanic responses induced by 4-methylesculetol in amphibian isolated neuromuscular preparations]. / Facilitazioni sull'insorgenza delle risposte tetaniche indotte dal 4-metilesculetolo in preparati neuromuscolari isolati di anfibio.

Previous observations have shown that the 4-Methylesculetin (4ME) and the calcium provoke an increased response when the motor somatic and autonomic nerve-endings are stimolated. In the present research, we have studied the influence of the bioflavonoid and of an increased medium [Ca++] on the tetanic responses obtained from the isolated frog "sciatic nerve-gastrocnemius muscle" preparation. The 4ME has always facilitated the beginning of a complete tetanic response and has also frequently increased the developed mechanical tension. These effects appeared more evident when the bioflavonoid was employed together with the ascorbic acid. Moreover, an increased medium [Ca++] has induced similar effects. The nifedipine and the flunarizine, well-known Ca++ -antagonists, have constantly reduced or even abolished the facilitating effect induced by the bioflavonoid. On the basis of these results, we could hypothize that these observed facilitating effects are dependent on both an increased Ach-release and an increased muscle mechanical efficiency. Our previous results and also some literature data suggest that these effects could be due to an increased Ca++-passage through the cell membrane of the motor nervendings and of the muscle fibres too.