HPV DNA testing in cervical cancer screening - Results from women in a high-risk province of Costa Rica

Context Human papillomaviruses (HPVs) are known to cause most cervical canc er worldwide, but the utility of HPV DNA testing in cervical cancer prevent ion has not been determined. Objective To provide comprehensive data on the screening performance of HPV testing for the most common carcinogenic types, at different levels of ana lytic sensitivity. Design Laboratory analysis conducted during 1993-1995, using 3 cytologic te chniques and cervicography, followed by colposcopic examination of women wi th any abnormal cervical finding, to detect all high-grade intraepithelial lesions and cancer (reference standard of clinically significant disease). The HPV testing was performed subsequently with masking regarding clinical findings. Setting Guanacaste Province, Costa Rica, a region with a high age-adjusted incidence of cervical cancer. Participants Of 11742 randomly selected women, 8554 nonpregnant, sexually a ctive women without hysterectomies underwent initial HPV DNA testing using the original Hybrid Capture Tube test; a stratified subsample of 1119 speci mens was retested using the more analytically sensitive second generation a ssay, the Hybrid Capture II test. Main Outcome Measures Receiver operating characteristic analysis of detecti on of cervical high-grade intraepithelial lesions and cancer by HPV DNA tes ting based on different cut points of positivity. Results An analytic sensitivity of 1.0 pg/mL using the second generation as say would have permitted detection of 88.4% of 138 high-grade lesions and c ancers (all 12 cancers were HPV-positive), with colposcopic referral of 12. 3% of women. Papanicolaou testing using atypical squamous cells of undeterm ined significance as a cut point for referral resulted in 77.7% sensitivity and 94.2% specificity, with 6.9% referred. Specificity of the second gener ation assay for positivity for high-grade lesions and cancer was 89.0%, wit h 33.8% of remaining HPV DNA-positive subjects having low-grade or equivoca l microscopically evident lesions. The higher detection threshold of 10 pg/ mL used with the original assay had a sensitivity of 74.8% and a specificit y of 93.4%, Lower levels of detection with the second generation assay (<1 pg/mL) proved clinically nonspecific without gains in diagnostic sensitivit y, Conclusions In this study population, a cut point of 1.0 pg/mL using the se cond generation assay permitted sensitive detection of cervical high-grade lesions and cancer, yielding an apparently optimal trade-off between high s ensitivity and reasonable specificity for this test. The test will perform best in settings in which sensitive detection of high-grade lesions and can cer is paramount. Because HPV prevalence varies by population, HPV testing positive predictive value for detection of high-grade lesions and cancer wi ll vary accordingly, with implications for utility relative to other cervic al cancer screening methods.