Study Of Cervical Cancer Screening Methods And Stratigies

Objectives:To evaluate multiple screening methods systemically and specificly and explore various screening strategies suitable for regions with different resource settings, and promote the prevention and control of cervical cancer to achieve the aim of decreasing the incidence and mortality of cervical cancer in China.Materials and Methods:Data were collected from 18 cross-sectional population-based studies conducted by CICAMS and its national or international collaborators in 10 provinces, which including 5 urban areas and 9 rural areas during 1999 to 2008. The performance of liquid based cytology (LBC), visual inspection with 5% Acetic acid staining (VIA) or Lugol's Iodine (VILI) and HPV DNA test (hc2), such as sensitivity (Se), specificity (Sp), et al. were analyzed by Pooled analysis. Specific research on LBC, VIA/VILI, and HPV DNA test were performed based on data from several projects and rural demonstration site for early diagnosis and treatment of cervical cancer in order to explore factors affect screening effectiveness. The clinical accuracy of new HPV-DNA test was tested in a cross-sectional population based study. Considering various health-resource settings, several screening algorithms were developed by combining screening tests in parallel or in serial, and their accuracy were evaluated by pathology.Results:1. Overall performance of screening tests:1) Se and Sp for LBC detecting CIN 2+ were 80.7% and 95.6%, respectively.2) Se and Sp for VIA detecting CIN 2+ were 48.2% and 90.5%, Se and Sp for VIA/VILI detecting CIN 2+ were 55.0% and 90.4%, Se among women older than 50 years decreased to 24.0%.3) Se and Sp for HPV DNA (hc2) detecting CIN 2+ were 96.3% and 86.0%.2. Specific performance of screening tests:1) Se for LBC without quality control (QC) detecting CIN 2+ were 62.2% and increased to 88.9% after QC, Sp was changed from 98.6% to 96.0% after QC, among the 11 unsatisfactory before QC, one CIN 2,3 cases CIN 3 and one SCC were diagnosed by pathology.2) In each age group of HPV positive women, there was a positive correlation between the risk of CIN 2+ and viral load (P<0.01), the risk of CIN2+ was highest among women aged 40-44 with high viral load [OR(95%CI):2.02 (1.15 - 3.52)].3) VIA/VILI was the primary screening test for cervical cancer rural demonstration site,53.4% of CIN 2,67.9% of CIN 3 and 91.7% of early stage cancer were detected by the first round screening, only one CIN 2 was found during the third round among the population screened consecutively three times.3. Clinical trial of new screening test:Se and Sp for physician-sampled careHPVTM detecting CIN 2+ were 90.0% and 84.2%, there was no significant difference compared to hc2 test, Se and Sp for self-sampled careHPVTM detecting CIN 2+ were 81.4% and 82.4%, respectively.4. Screening algorithms study:1) Se, Sp and colposcopy referral rate (CRR) for LBC as primary screening test with ASC-US women triage by HPV DNA testing were 93.0%, 89.9% and 13.7%, for HPV DNA testing as the primary screening test with HPV positive women triage by LBC were 91.7%,93.0% and 10.6%.2) Se, Sp and CRR for solely LBC (≥ASC-US) were 94.2%,77.3% and 25.7%, for LBC (≥LSIL) were 87.2%,93.5% and 10.0%, for solely physician-sampled HPV DNA test were 97.6%,84.8% and 18.8%, for solely self-sampled HPV DNA test were 83.5%,85.9% andl7.1%.3) Se, Sp and CRR for solely VIA were 70.9%,74.3% and 27.6%, and for HPV primary testing followed by VIA triage were 65.9%,95.2% and 7.4%.Conclusions:1. The study performed a systematic evaluation on multiple screening tests in order to explore different screening strategies according to various resource settings. Sampling and reading are the major factors of false negative of LBC, screening effectiveness only can be achieved by training and QC; HPV DNA test is high sensitive, moderate specific, objective and reproducible screening method, a low cost and rapid HPV test (careHPVTM) is a better alternative screening method due to high cost of hc2; VIA is simple and independent on equipment and resources, but is subjective, needs intense training, its sensitivity could be improved by adding VILI, twice screening can help to increase the detection rate of precancerous lesions.2. 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 feasible primary screening test in less developed regions before careHPVTM is available, and HPV primary testing followed by VIA triage will be more appropriate for the areas lack of colposcopy and doctors.