Testing optional screening tools for cervical cancer in the new independent states (NIS) of the former Soviet Union

Background and Objective: The incidence and mortality rates of cervical cancer are rapidly rising in the new independent states (NIS) of the former Soviet Union. Am EC-funded (INCO-COPERNICUS) cross-sectional and cohort study was recently completed, analyzing the performance of HPV test (HCII) as a potential screening tool for cervical cancer in these countries. Methods: A series of 3.187 women (screening-, gynecological-, and STD patients) from six clinics in Russia, Belarus and Latvia received routine cytology and HPV testing with Hybrid Capture II (HC II). Women with HPV positive results or abnormalities in cytology were examined by colposcopy and biopsy. The performance characteristics (SP, SE, PPV, NPV, ROC) were calculated for HCII and PAP smear cytology. Results: Pap smear cytology detected high-grade lesions with sensitivity of 64.0% (44.8-83.2), specificity 89.1% (84.5-93.7), PPV 44.4% (28.8-61.0) and NPV% 94.8 (91.2-98.4). Of the 3.086 samples analyzed by HCII, 32.8% were positive for oncogenic HPV types, with a wide variation (from 24.7% to 45%) between the three diagnostic categories (P<0.0001). The presence of high-grade cytology was significantly associated with HCII-positivity at all cut-off levels (OR 12,0 95% CI 8.5 to 16,9; Chi-square p<0.0001; 1pg/ml threshold). In ROC curve, the HCII cut-off point most closely balancing the sensitivity (82.0%) and specificity (80.3%) in detecting significant cytology was 10pg/ml (area under ROC curve 0.867, 95% CI 0.834-0.900). The presence of high-grade histology was associated with HCII-positivity (cut-off 1pg/ml)(OR 2.6, 95% CI 1,3 to 5.3; p=0.002). At the cutoff (1pg/ml), sensitivity of HCII test in detecting significant histology (CINII or higher) was 95.7%, specificity 17.4%, PPV 23.4% and NPV 93.9%. The figures for detecting high-grade cytology were: 87.7%, 69.5%, 11.5%, and 99.2%, respectively. Conclusions: HCH assay is more sensitive but less specific than PAP test in detecting significant pathology. Negative HCII test practically pre-eludes high-grade SIL (NPV >99%). The cost-benefit issues in different settings will be the critical factor for the adoption of this test as a screening tool.