A study of cervical cancer screening algorithms

Abstract

To assess the feasibility and accuracy of different cervical cancer screening algorithms suitable for different regions, and promote the prevention and control of cervical cancer in China. Using the data of a cross-sectional comparative trial of multiple techniques to detect cervical intraepithelial neoplasia in Xiangyuan County, Shanxi Province, conducted in 1999, to evaluate the feasibility and accuracy of different cervical cancer screening algorithms. All the women were screened by six screening tests, including liquid based cytology (LBC), fluorescence spectroscopy, visual inspection with 5% acetic acid staining (VIA), colposcopy, self-sampled HPV DNA and clinician-sampled HPV DNA test, and each woman had histopathological diagnosis. Different screening algorithms were developed by combining the screening tests in parallel or in serial, and the performance indexes of the algorithms such as sensitivity, specificity, colposcopy referral rate and receiver operating characteristic (ROC) curve for detecting the high grade lesions (>or= CIN 2) were compared. Among the algorithms combined by LBC and HPV DNA testing, for the combination in parallel (either cytology was greater than ASC-US or HPV positives), its sensitivity was 100%, specificity was 68.6%, and colposcopy referral rate was 34.4%; for the algorithm of LBC as primary screening test, with ASC-US women triage by HPV DNA testing, its sensitivity was 93.0%, specificity was 89.9%, and colposcopy referral rate was 13.7%; for the algorithm of HPV DNA testing as the primary screening test, with HPV positive women triage by LBC, its sensitivity was 91.7%, specificity was 93.0%, and colposcopy referral rate was 10.6%. ROC analysis showed that LBC primary testing followed by HPV triage and HPV primary testing followed by LBC triage were much better than the combination in parallel (P = 0.0003, P = 0.0002). Among the algorithms with LBC or HPV DNA testing solely as primary screening test, the sensitivity, specificity and colposcopy referral rate of LBC were 94.2%, 77.3%, 25.7% and 87.2%, 93.5%, 10.0%, respectively, for cutoff by ASC-US or by LSIL; the sensitivity, specificity and colposcopy referral rate of HPV DNA testing were 97.6%, 84.8%, 18.8% and 83.5%, 85.9%, 17.1%, respectively, for clinician-sampled and self-sampled. Clinician-sampled HPV DNA testing was better than LBC cutoff by ASC-US or self-sampled HPV DNA testing (P = 0.005, P = 0.002). Among the algorithms combined by VIA and HPV DNA testing, the sensitivity, specificity and colposcopy referral rate were 70.9%, 74.3% and 27.6% for VIA alone as primary screening test; the sensitivity, specificity and colposcopy referral rate were 65.9%, 95.2% and 7.4% for HPV as primary screening test with HPV positive women triage by VIA. HPV primary testing followed by VIA triage was better than VIA alone (P = 0.004). Considering the health-resource settings and women's preference, both HPV primary testing followed by LBC triage and LBC primary testing followed by HPV triage are suitable for developed regions, moderately developed regions may choose either LBC or HPV as the screening approach, VIA is a suitable primary screening test in less developed regions, and HPV primary testing followed by VIA triage will be more effective if low cost HPV test is available in the future.