T he primary screening of cancer of the uterine cervix is based in most countries on Pap cytology testing. Women with an abnormal cytology are referred for colposcopy-directed biopsy to assess the presence and grade of cervical disease. In North America, for each new case of cervical cancer, there are between 50 and 100 cases of abnormal smears consistent with low-grade (LSIL) or high-grade squamous intraepithelial lesions (HSIL) (11). Additionally, there are at least twice as many cases of "atypical squamous cells of undetermined significance" (ASC-US). Up to 15% of women with ASC-US have underlying high-grade cervical intraepithelial neoplasia 2 (CIN2) or CIN3 (2). Three clinical options have been proposed by the American Society for Colposcopy and Cervical Pathology to refer women with ASC-US to colposcopy, namely, repeat cytology, immediate referral to colposcopy, and reflex testing with generic assays for detection of high-risk (HR) human papillomavirus (HPV) genotypes (7, 21).When liquid-based cytology is used or when cocollected samples for cytology and HR HPV DNA testing can be obtained, HR HPV testing is the preferred triage approach (21). Since the introduction of the Hybrid Capture 2 assay (HC2; Qiagen, Inc., Mississauga, Ontario, Canada), several new HPV generic assays have been developed for the detection of HR HPV for ASC-US triage (17). The cobas 4800 HPV test (Roche Diagnostics, Laval, Québec, Canada) is a novel assay that detects HPV66 in addition to the 13 HR HPV genotypes detected by HC2. Nevertheless, HPV66 is detected by HC2 due to cross-hybridization (7). One report found that cross-reactivity with low-risk genotypes was more frequently encountered with HC2 than with the cobas 4800 HPV test (14). Few studies have evaluated the screening performance of the cobas 4800 HPV test (4,6,12,14,15,19,22).In this work, we compared the clinical performance of cobas 4800 HPV to that of HC2 on clinical specimens collected from women referred for colposcopy because of an ASC-US smear. HPV genotypic analysis was also performed with the Linear Array HPV genotyping (LA) assay (Roche Diagnostics, Laval, Canada) on all samples to assess cross-reactivity of the HPV generic assays. MATERIALS AND METHODSStudy design and population. Participants were recruited consecutively from December 2005 to December 2007 if they were referred for colposcopy because of at least one ASC-US cytology, were Ն24 years old, and had not received treatment for CIN in the last 2 years (10). Cervical cells were first collected with a Cytobrush for a conventional cytology. A second cervical specimen was collected with a Cytobrush prior to colposcopic examination. The Cytobrush was washed into PreservCyt collection medium (Hologic, Inc., Marlborough, MA) and kept at room temperature for 1 week and at Ϫ20°C thereafter. Samples in PreservCyt were processed for HPV DNA testing within 1 week for HC2 testing and LA and 3 to 5 years later depending on patients' inclusion dates for cobas 4800 HPV (Roche Diagnostics) testing. Colposcopy-guided b...

Up to 20% of women having a cytology smear showing atypical squamous cells of undetermined significance (ASC-US) and infected with high-risk human papillomavirus (HR HPV) have high-grade cervical intraepithelial neoplasia (CIN 2/3). Results obtained with theHigh-risk human papillomavirus (HR HPV) genotypes are associated with high-grade cervical intraepithelial neoplasia (CIN 2/3) and cancer of the uterine cervix (2, 3). Primary screening of cervical cancer is essentially based on Pap cytology testing. In North America, for each new case of cervical cancer screened by cytology, there are between 50 and 100 cases of abnormal smears consistent with low-grade squamous intraepithelial lesions (LSIL) or high-grade squamous intraepithelial lesions (HSIL) (9). Additionally, there are at least twice as many cases of equivocal or borderline atypias, referred to as "atypical squamous cells of undetermined significance" (ASC-US). Three options have been proposed by the American Society for Colposcopy and Cervical Pathology to perform triage on women with ASC-US, namely, repeat cytology, immediate referral to colposcopy, and reflex HR HPV testing (28).The most widely used HR HPV detection assay for the triage of women with ASC-US is the Hybrid Capture 2 assay (HC-2; Qiagen, Inc., Mississauga, Ontario, Canada) (15). The HC-2 and Amplicor HPV (Roche Diagnostics, Laval, Quebec, Canada) tests detect the same 13 HR genotypes and are approved by Health Canada for clinical use. Several studies have evaluated the Amplicor HPV test, but only one analyzed fresh samples collected from women with ASC-US (4,11,14,15,25,26,27). The evaluation of the performance of the Amplicor HPV test in a diagnostic setting is mandatory to assess its utility in the management of women with ASC-US. We evaluated the clinical performance of two generic HPV assays, Amplicor HPV and HC-2, on fresh clinical specimens obtained prospectively from women referred to colposcopy because of an ASC-US cytology result. HPV genotypic analysis was performed on all samples to assess the cross-reactivity of the HPV generic assays. MATERIALS AND METHODSStudy design and population. Participants were recruited consecutively if (i) they were referred to colposcopy because of at least one ASC-US cytology, (ii) were Ն24 years old, and (iii) had not received treatment for CIN in the last 2 years. During the study period, HPV DNA testing was not widely available to primary care physicians in the study area and women were referred to colposcopy