Comparison of human papillomavirus DNA testing and repeat Papanicolaou test in women with low-grade cervical cytologic abnormalities: a randomized trial

Background: Results of cervical cytology screening showing atypical squamou s cells of undetermined significance (ASCUS) or low-grade squamous intraepi thelial lesions (LSIL) indicate risk for high-grade cervical intraepithelia l neoplasia (CIN 2 or 3). In a community-based randomized trial we compared the test performance of human papillomavirus (HPV) DNA testing with that o f 6-month repeat Papanicolaou (Pap) test in detecting histologically confir med CIN 2 or 3. Methods: We randomly assigned 212 women aged 16-50 years with ASCUS or LSIL on cervical cytology screening to undergo either immediate HPV DNA testing or a repeat Pap test in 6 months. Cervical swabs for the HPV DNA testing a nd the Pap smears were obtained by their familiy physicians. We tested the swabs for oncogenic HPV using the Hybrid Capture II assay (Digene Corp., Be ltsville, Md.). Community-based pathologists examined the Pap smears. All w omen were referred for colposcopy by their family physicians. Two gynecolog ical pathologists assessed the histology findings. We calculated test perfo rmance in women who completed the trial using CIN 2 or 3 as the reference s tandard, Results: A total of 159 women completed the study. Compared with HPV DNA te sting, which detected 87.5% (7/8) of the cases of CIN 2 or 3, repeat Pap sm ear showing high-grade intraepithelial neoplasia (HSIL) detected 11.1%(1/9) of cases (p = 0.004), and repeat Pap smear showing ASCUS, LSIL or HSIL dete cted 55.6% (5/9) (p = 0.16). Corresponding specificities were 50.6%, 95.2% (p = 0.002) and 55.6% (p = 0.61). Loss to follow-up was 17.1% in the HPV te st group and 32.7% in the repeat Pap group (p = 0.009). Given the 7 cases o f CIN 2 or 3 detected by HPV testing and the 5 cases detected by the repeat Pap smear, the incremental cost of HPV testing was calculated to be $3003 per additional case of CIN identified. Interpretation: HPV DNA testing was more costly but was associated with sig nificantly less loss to follow-up. It may detect more cases of CIN 2 or 3 i n women with low-grade cytologic abnormalities.