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.

Concentrations of polychlorinated dibenzodioxins, polychlorodibenzofurans, and polychlorobiphenyls in women of reproductive age in Italy: A human biomonitoring study.

BACKGROUND: Polychlorinated dibenzodioxins (PCDDs), polychlorodibenzofurans (PCDFs), and polychlorobiphenyls (PCBs) are persistent organic pollutants that represent a major concern for women of reproductive age because of the neurodevelopmental effects associated to perinatal exposure. OBJECTIVES: This study was aimed at characterizing exposure of women of reproductive age to PCDDs, PCDFs, and PCBs as a function of residence in different Italian Regions, in areas at presumable different environmental contamination and human exposure to these pollutants. METHODS: Study participants were enrolled in 2011-2012 in 6 Italian Regions representative of Northern, Central and Southern Italy; in each region, areas at presumed different exposure (rural, urban and industrial) were selected for enrolment. Each participant provided a serum sample for the analysis of PCDDs, PCDFs and PCBs. RESULTS: Median concentrations of PCDDs+PCDFs, DL-PCBs, NDL6-PCBs and NDL9-PCBs in serum samples were respectively 6.0 and 3.5 pgWHO-TE05/g fat, and 75 and 93ng/g fat. Age was the variable that most affected median serum concentrations. Age adjusted concentrations were found significantly different between geographical zones: women from Northern Italy showed the highest values, followed by Central and Southern Italy. PCDDs+PCDFs concentrations were significantly higher in the group of women residing in industrial areas compared to the group residing in rural areas. A clear diminishing temporal trend was observed compared to levels reported in previous studies. CONCLUSIONS: This study produced the largest dataset on serum concentrations of PCDDs, PCDFs and PCBs in women of childbearing age in Italy. RESULTS: confirmed that environmental and lifestyle factors may influence exposure to these contaminants and thereby the body burden. The observed marked temporal decline in body burden during three decades is in agreement with the general trend observed worldwide.