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BACKGROUND Although delay to diagnosis after a breast screening abnormality causes anxiety, its effect on prognosis is unknown. METHODS Using pooled data from five Canadian organized breast cancer screening programs, the authors used unconditional logistic regression to evaluate the effect of delay to diagnosis on prognostic indicators among 4465 women with invasive breast carcinoma diagnosed in the ipsilateral breast within 3 years of an abnormal screen performed during 1990–1996. RESULTS Women with high‐suspicion screens (n = 1569) compared with those without (n = 2896) were more promptly investigated (median days from screen to diagnosis, 31 vs. 47; P ≤ 0.0001), had larger tumors (79.4% vs. 55.9% > 10 mm; P ≤ 0.0001), and were more likely to be lymph node positive (33.9% vs. 17.3%; P ≤ 0.0001). For delays beyond > 12 to ≤ 20 weeks, a linear trend of increased tumor size and lymph node positivity began to emerge. Controlling for suspicion, the authors found that odds ratios for tumor size greater than 10 mm were 0.9 (95% CI, 0.66–1.17), 1.2 (95% confidence interval [CI], 0.88–1.56), 1.5 (95% CI, 1.05–2.16), and 2.1 (95% CI, 1.15–3.86) for delays of > 12 to ≤ 20, > 20 to ≤ 52, > 52 to ≤ 104, and > 104 ≤ 156 weeks, respectively (ptrend ≤ 0.0001), compared with delays of > 4 to ≤ 12 weeks. Similarly, odds ratios for lymph node metastasis were 1.0 (95% CI, 0.67–1.42), 1.2 (95% CI, 0.84–1.69), 2.2 (95% CI, 1.48–3.15), and 3.2 (95% CI, 1.84–5.55) for the same time intervals (ptrend = 0.0033). CONCLUSIONS The authors' findings suggest that delays to diagnosis of asymptomatic breast carcinoma of 6 to 12 months are associated with progression of breast carcinoma as measured by increasing risk of lymph node metastases and larger tumor size. A policy of early recall rather than biopsy for low suspicion mammographic abnormalities may introduce delays of this magnitude. The tendency to more expediently investigate women with high‐suspicion, worse prognosis screens (suspicion bias) obscures whether delays shorter than 20 weeks also worsen prognostic indicators. Suspicion bias should be considered when interpreting the effect of delay on prognosis. Cancer 2002;94:2143–50. © 2002 American Cancer Society. DOI 10.1002/cncr.10453

Background:Round 1 data of human papillomavirus (HPV) FOCAL, a three-arm, randomised trial, which aims to establish the efficacy of HPV DNA testing as a primary screen for cervical cancer, are presented.Methods:The three arms are: Control arm – liquid based cytology with atypical squamous cells of unknown significance (ASC-US) triage with hrHPV testing; Intervention Arm – hrHPV at entry with liquid-based cytology (LBC) triage of hrHPV positives, with exit screen at 4 years; Safety check arm – hrHPV at entry with LBC triage of hrHPV positives with exit screen at 2 years.Results:A total of 6154 women were randomised to the control arm and 12 494 to the HPV arms (intervention and safety check). In the HPV arm, the baseline cervical intraepithelial neoplasia (CIN)2+ and CIN3+ rate was 9.2/1000 (95%CI; 7.4, 10.9) and 4.8/1000 (95%CI; 3.6, 6.1), which increased to 16.1/1000 (95%CI 13.2, 18.9) for CIN2+ and to 8.0/1000 (95%CI; 5.9, 10.0) for CIN3+ after subsequent screening of HPV-DNA-positive/cytology-negative women. Detection rate in the control arm remained unchanged after subsequent screening of ASC-US-positive/hrHPV DNA-negative women at 11.0/1000 for CIN2+ and 5.0/1000 for CIN3+.Conclusion:After subsequent screening of women who were either hrHPV positive/cytology negative or ASC-US positive/HPV negative, women randomised to the HPV arms had increased CIN2+ detection compared with women randomised to the cytology arm.

BackgroundIn the HPV FOCAL trial, we will establish the efficacy of hr-HPV DNA testing as a stand-alone screening test followed by liquid based cytology (LBC) triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with ≥ CIN3 as the outcome.Methods/DesignHPV-FOCAL is a randomized, controlled, three-armed study over a four year period conducted in British Columbia. It will recruit 33,000 women aged 25-65 through the province's population based cervical cancer screening program. Control arm: LBC at entry and two years, and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases; Two Year Safety Check arm: hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives; Four Year Intervention Arm: hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive casesDiscussionTo date, 6150 participants have a completed sample and epidemiologic questionnaire. Of the 2019 women enrolled in the control arm, 1908 (94.5%) were cytology negative. Women aged 25-29 had the highest rates of HSIL (1.4%). In the safety arm 92.2% of women were hr-HPV negative, with the highest rate of hr-HPV positivity found in 25-29 year old women (23.5%). Similar results were obtained in the intervention arm HPV FOCAL is the first randomized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population-based cervical cancer screening program.Trial RegistrationInternational Standard Randomised Controlled Trial Number Register, ISRCTN79347302

Standardized abnormal interpretation ratios and standardized cancer detection ratios provide a method of comparing two important performance measures in a screening program. A minimum of 2,500 interpretations per year is associated with lower abnormal interpretation rates and average or better cancer detection rates.