Identifying women with cervical neoplasia - Using human papillomavirus DNAtesting for equivocal Papanicolaou results

Context A Papanicolaou (Pap) test result of atypical squamous cells of unde termined significance (ASCUS) presents a clinical challenge. Only 5% to 10% of women with ASCUS harbor serious cervical disease, but more than one thi rd of the high-grade squamous intraepithelial lesions (HSILs) in screening populations are identified from ASCUS Pap test results. Objective To determine whether human papillomavirus (HPV) DNA testing of re sidual material from liquid-based Pap tests and referral of cases found to be HPV-positive directly to colposcopy could provide sensitive detection of underlying HSILs in women with ASCUS Pap results, compared with repeat Pap testing. Design and Setting Natural history of women with ASCUS Pap smear results, a ll of whom had liquid-based cytology, HPV testing, and subsequent repeat Pa p tests and colposcopy with histologic evaluation, conducted at 12 gynecolo gy clinics in a targe managed care organization between October 1995 and Ju ne 1996. Participants From a cohort of 46 009 women who had routine cervical examina tions, 995 women with Pap test results of ASCUS who consented to participat e were identified. Main Outcome Measures Cervical histology, HPV test results, and repeat Pap smear results, and sensitivity of HPV testing to identify patients found to have HSIL+ histology. Results Of 995 participants with ASCUS Pap test results, 973 had both a def initive histologic diagnosis and HPV result. Sixty-five (6.7%) had histolog ic HSIL or cancer. For women with histologic HSIL+, the HPV test was positi ve in 89.2% (95% confidence interval [CI], 78.4%-95.2%), and the specificit y was 64.1% (95% CI, 60.9%-67.2%). The repeat Pap smear result was abnormal in 76.2% (95% CI, 63.5%-85.7%). Triage based on HPV testing only or on rep eat Pap testing only would refer similar proportions (approximately 39%) to colposcopy. The sensitivity of HPV DNA testing for HSIL was equivalent to, if not greater than, that of the repeat Pap test. We further estimated tha t an HPV-based algorithm including the immediate colposcopy of HPV-positive women, and then repeat Pap testing of all others, would provide an overall sensitivity of 96.9% (95% CI, 88.3%-99.5%). Conclusions For women with ASCUS Pap tests, HPV DNA testing of residual spe cimens collected for routine cervical cytology can help identify those who have underlying HSIL. By testing the specimen collected at initial screenin g, the majority of highrisk cases can be identified and referred for colpos copy based on a single screening.