Accuracy of different triage strategies for human papillomavirus positivity in an Italian screening population.

How to manage human papillomavirus (HPV)-positive women in cervical cancer screening remains debated. Our study compared different strategies to triage HPV positivity in a large cohort of women participating in a population HPV-based screening program. Women were tested for HPV (Cobas 4800; Roche), and those positive were triaged with cytology; cytology-positives were referred to colposcopy, while negatives were referred to 1-year HPV retesting. All HPV-positive women were also evaluated with p16/ki67 dual staining (Roche). All lesions found within 24 months of follow-up were included in the analyses. Of the 70 146 women tested, 4757 (6.8%) were HPV-positive. Of these, 1090 were cytology-positive and were referred to colposcopy. Of the 2958 HPV-positive/cytology-negative women who presented at 1-year retesting, 1752 (59.9%) still tested positive. Cumulatively, 532 CIN2+ (including 294 CIN3+) were found. The sensitivity of cytology, HPV16/18 and p16/ki67 as triage test for CIN3+ was 67.9%, 56.0% and 85.0%, respectively. The positive predictive value (PPV) for immediate colposcopy referral was 21.0%, 15.8% and 22.9%, respectively. Combining cytology with typing increased sensitivity to 83.9% and lowered PPV to 14.8%, while combining p16/ki67 and typing increased sensitivity to 91.1%, lowering the PPV to 15.9%. Women negative to p16/ki67 triage presented a cumulative 1-year CIN3+ risk of about 1%. In conclusion, when triaging HPV positivity, p16/ki67 performed better than cytology with or without HPV16/18 genotyping. The strategies that included dual staining achieved sensitivity and low 1-year risk for CIN3+ sufficiently high enough to permit considering extending the surveillance interval to 2 to 3 years for HPV-positive/triage-negative women.

A web-based tumor registration system for a regional Canine Cancer Registry in Umbria, central Italy.

The Umbria Canine Cancer Registry (CCR) is a web-based platform for cancer registration set up in order to estimate the incidence of spontaneous tumors. It is an integral part of the regional canine demographic registry in which veterinary practitioners and pathologists interact. Veterinary pathologists perform double-blind comparisons and classify neoplasms in an automated classification process using the WHO criteria for canine neoplasms and the ICD-O tumor topographical and morphological keys. Here we describe the organization, on-line procedures and the methods used to assess canine demography, a pre-requisite for accurately estimating the incidence of cancer. In its first 4 years the CCR recruited 4857 cases of suspected tumors, as diagnosed by practitioners, clinics and a veterinary hospital. After the first year the number of enrolled cases increased by 63%, suggesting growing interest from the regional veterinary community.

Cervical human papilloma virus (HPV) DNA primary screening test: Results of a population-based screening programme in central Italy.

Objective To present the results of the first and second round human papilloma virus (HPV)-based screening programme in the Umbria region after three years. Methods From August 2010 to November 2011, the entire female population aged 35-64 in a local health district was invited for HPV testing (HPV-DNA cobas4800 on a liquid-based cytology sample). HPV-negative women were re-invited after three years. For HPV-positive women, a slide was prepared and interpreted. Positive cytologies were referred to colposcopy; negatives were referred to repeat HPV after one year. If HPV was persistently positive, women were referred to colposcopy; if negative, to normal screening. Indicators of the first and second round are compared with those of cytology screening in the same area in the preceding three years. Results Participation was 56.5%, the same as cytology (56.6%). HPV-positivity was 6.4% (396/6272), cytology triage positivity was 35.6%; 251 cytology negative women were referred to one-year HPV retesting, 84.1% complied, and 55.5% were positive. Total colposcopy referral was 4.1%, and for cytology 1%. The detection rate for cervical intraepithelial neoplasia grade 2 or more severe was 10‰, compared with 3.7‰ using cytology. After three years, HPV-positivity was 3.4% (129/3831), overall colposcopy referral was 2.3% (most at one-year follow-up), and detection rate was 0.5/1000. Conclusions The first round detection rate was more than twice that of cytology screening, while colposcopy referral increased fourfold. At the second round, the detection rate decreased dramatically, showing that longer interval and more conservative protocols are needed.

Use of Cytology, E6/E7 mRNA, and p16INK4a-Ki-67 to Define the Management of Human Papillomavirus (HPV)-Positive Women in Cervical Cancer Screening.

OBJECTIVES: We measured the accuracy of p16(INK4a)-Ki67 (CINtec PLUS, Roche, Mannheim, Germany), and E6/E7mRNA (types 16/18/31/33/45 NucliSENS easyQ, bioMérieux, Boxtel, The Netherlands) as triage test, alone and combined with cytology. METHODS: Six thousand two hundred and seventy two women were recruited in a population-based screening using HPV DNA as primary test; 396 were positive and were tested for cytology and biomarkers. All tests were performed on the same sample. Cytology-positive women were referred to colposcopy; cytology-negative women were referred to one-year HPV re-testing. The endpoint was CIN2+ at baseline or follow up. RESULTS: Sensitivity was 77.6% (95% confidence interval (CI) 65.3-86.7) and 53.2% (95%CI: 40.3-65.4) for cytology at atypical squamous cells of undetermined significance (ASC-US) and high-grade threshold, and 87.6% (95%CI:75.7-93.6), and 80.8% (95%CI: 67.6-89.8) for p16INK4a-Ki67, and E6/E7mRNA, respectively. Colposcopy referral was 36% (95%CI: 31.2-40.9) and 11.2% (95%CI: 7.8-14.1) for cytology at ASC-US and high-grade threshold, respectively, and 36.0% (95%CI: 29.9-29.6), and 47.5% (95%CI: 32.5-42.4) for p16(INK4a)-Ki67, and E6/E7mRNA, respectively. Strategies referring high-grade cytology or biomarker positive women to colposcopy reached sensitivity close to 100%, with modest increase in colposcopy referral. CONCLUSIONS: The high sensitivity of combined strategies probably allows longer intervals in HPV-positive, triage-negative women.

Description of the EUROBIS program: a combination of an Epode community-based and a clinical care intervention to improve the lifestyles of children and adolescents with overweight or obesity.

The present paper describes the Epode Umbria Region Obesity Prevention Study (EUROBIS) and aims to implement the C.U.R.I.A.MO. model through the EPODE methodology. The main goal of the EUROBIS is to change the pendency of slope of the actual trend towards the increase in the yearly rates of childhood overweight and obesity in Umbria and to improve healthy lifestyles of children and their parents. The project is the first EPODE program to be performed in Italy. The aims of the Italian EUROBIS study are: (1) a community-based intervention program (CBP) carrying out activities in all primary schools of the Umbria Region and family settings as first step, to reverse the current obesity trend on a long-term basis, and (2) a clinical care program for childhood and adolescent by C.U.R.I.A.MO. model. C.U.R.I.A.MO. model is a multidisciplinary approach to improve three key aspects of healthy lifestyles: nutrition, exercise, and psychological aspects with the strategy of a family-based approach. The community-based intervention and clinical trial provide an innovative valuable model to address the childhood obesity prevention and treatment in Italy.