Manuel Zorzi

BACKGROUND: Although testing for human papillomavirus (HPV) has higher sensitivity and lower specificity than cytology alone for detecting cervical intraepithelial neoplasia (CIN), studies comparing conventional and liquid-based cytology have had conflicting results. METHODS: In the first phase of a two-phase multicenter randomized controlled trial, women aged 35-60 years in the conventional arm (n = 16,658) were screened using conventional cytology, and women in the experimental arm (n = 16,706) had liquid-based cytology and were tested for high-risk HPV types using the Hybrid Capture 2 assay. Women in the conventional arm were referred to colposcopy with atypical cells of undetermined significance (ASCUS) or higher and those in the experimental arm were referred with ASCUS or higher cytology or with a positive (> or = 1 pg/mL) HPV test. Sensitivity and positive predictive value (PPV) for detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were calculated. RESULTS: The screening methods and referral criterion applied in the experimental arm had higher sensitivity than that in the conventional arm (relative sensitivity = 1.47; 95% confidence interval [CI] = 1.03 to 2.09) but a lower PPV (relative PPV = 0.40; 95% CI = 0.23 to 0.66). With HPV testing alone at > or = 1 pg/mL and at > or = 2 pg/mL, the gain in sensitivity compared with the conventional arm remained similar (relative sensitivity = 1.43, 95% CI = 1.00 to 2.04 and relative sensitivity = 1.41, 95% CI = 0.98 to 2.01, respectively) but PPV progressively improved (relative PPV = 0.58, 95% CI = 0.33 to 0.98 and relative PPV = 0.75, 95% CI = 0.45 and 1.27, respectively). Referral based on liquid-based cytology alone did not increase sensitivity compared with conventional cytology (relative sensitivity = 1.06; 95% CI = 0.72 to 1.55) but reduced PPV (relative PPV = 0.57; 95% CI = 0.39 to 0.82). CONCLUSIONS: HPV testing alone was more sensitive than conventional cytology among women 35-60 years old. Adding liquid-based cytology improved sensitivity only marginally but increased false-positives. HPV testing using Hybrid Capture 2 with a 2 pg/mL cutoff may be more appropriate than a 1 pg/mL cutoff for primary cervical cancer screening.

OBJECTIVE: Colorectal cancer (CRC) screening programmes based on the guaiac faecal occult blood test (gFOBT) reduce CRC-specific mortality. Several studies have shown higher sensitivity with the faecal immunochemical test (FIT) compared with gFOBT. We carried out an ecological study to evaluate the impact of FIT-based screening programmes on CRC mortality. DESIGN: In the Veneto Region (Italy), biennial FIT-based screening programmes that invited 50-69-year-old residents were introduced in different areas between 2002 and 2009. We compared CRC mortality rates from 1995 to 2011 between the areas where screening started in 2002-2004 (early screening areas (ESA)) and areas that introduced the screening in 2008-2009 (late screening areas (LSA)) using Poisson regression models. We also compared available data on CRC incidence rates (1995-2007) and surgical resection rates (2001-2012). RESULTS: Before the introduction of screening, CRC mortality and incidence rates in the two areas were similar. Compared with 1995-2000, 2006-2011 mortality rates were 22% lower in the ESA than in the LSA (rate ratio (RR)=0.78; 95% CI 0.68 to 0.89). The reduction was larger in women (RR=0.64; CI 0.51 to 0.80) than in men (RR=0.87; CI 0.73 to 1.04). In the ESA, incidence and surgery rates peaked during the introduction of the screening programme and then returned to the baseline (2006-2007 incidence) or dropped below initial values (surgery after 2007). CONCLUSIONS: FIT-based screening programmes were associated with a significant reduction in CRC mortality. This effect took place much earlier than reported by gFOBT-based trials and observational studies.

BACKGROUND: In the first recruitment phase of a randomized trial of cervical cancer screening methods (New Technologies for Cervical Cancer Screening [NTCC] study), we compared screening with conventional cytology with screening by human papillomavirus (HPV) testing in combination with liquid-based cytology. HPV-positive women were directly referred to colposcopy if aged 35 or older; if younger, they were retested after 1 year. METHODS: In the second recruitment phase of NTCC, we randomly assigned women to conventional cytology (n = 24,661) with referral to colposcopy if cytology indicated atypical squamous cells of undetermined significance or more severe abnormality or to testing for high-risk HPV DNA alone by Hybrid Capture 2 (n = 24,535) with referral to colposcopy if the test was positive at a concentration of HPV DNA 1 pg/mL or greater. For the main endpoint of the study, histologic detection of cervical intraepithelial neoplasia of grade 2 or more (CIN2+), we calculated and compared sensitivity and positive predictive value (PPV) of the two screening methods using HPV DNA cutoffs of 1 pg/mL and 2 pg/mL. All statistical tests were two-sided. RESULTS: For women aged 35-60 years, the relative sensitivity of HPV testing for detection of CIN2+ at a cutoff of 1 pg/mL vs conventional cytology was 1.92 (95% CI = 1.28 to 2.87) and the relative PPV was 0.80 (95% CI = 0.55 to 1.18). At a cutoff of 2 pg/mL HPV DNA, the relative sensitivity was 1.81 (95% CI = 1.20 to 2.72) and the relative PPV was 0.99 (95% CI = 0.67 to 1.46). In this age group, there was no evidence of heterogeneity between study phases. Among women aged 25-34 years, the relative sensitivity for detection of CIN2+ of HPV testing at a cutoff of 1 pg/mL vs cytology was 3.50 (95% CI = 2.11 to 5.82), statistically significantly larger (P = .019) than that observed in phase 1 at this age (1.58; 95% CI = 1.03 to 2.44). CONCLUSIONS: For women aged 35-60 years, HPV testing with a cutoff of 2 pg/mL achieves a substantial gain in sensitivity over cytology with only a small reduction in PPV. Among women aged 25-34 years, the large relative sensitivity of HPV testing compared with conventional cytology and the difference between relative sensitivity during phases 1 and 2 suggests that there is frequent regression of CIN2+ that are detected by direct referral of younger HPV-positive women to colposcopy. Thus, triage test or repeat testing is needed if HPV is to be used for primary testing in this context.