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To provide realistic estimates of effectiveness for new screening programs, we studied ICC risk after a 7\u2010year repeated multimethod screening effort. In 1993\u20131994, 10,049 women aged 18\u201397\u00a0years were enrolled into a population\u2010based cohort study of cervical HPV in Guanacaste, Costa Rica. Women were screened at different intervals according to enrollment results. Each visit (mean 3.2, 90% attendance) included split\u2010sample conventional, automated, and liquid\u2010based cytology, visual inspection, cervicography, and PCR\u2010based HPV testing. Abnormal screening led to colposcopy and excisional treatment as appropriate during the study. Referral to colposcopy for HPV in the absence of other findings was introduced only at the last visit. Population\u2010based Costa Rica Cancer Registry linkage identified cohort women diagnosed with ICC in the 18\u00a0years following cohort enrollment. The ICC cumulative risk was 0.4% (<jats:italic>n<\/jats:italic>\u00a0=\u00a038); 18 were diagnosed with ICC after study participation. Of these, 9 were missed at the screening step (negative screening or below the referral threshold, refused screening or colposcopy), 5 attended colposcopy but were not diagnosed as CIN2+, and 4 were treated for CIN2\/3 but progressed to ICC nonetheless. Decreasing age\u2010standardized ICC rates for the 1993\u20132011 period were observed in Guanacaste; cohort women showed additional 31% ICC incidence reduction with apparent downstaging of cancers that occurred. ICC risk following negative HPV testing in the optimal age range 30\u201350\u00a0years was extremely low. 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