Update on recent clinical studies using HPV testing for screening and diagnosis of cervical neoplasia

Because HPV is the primary etiologic agent in cervical cancer, HPV testing may be useful for cervical cancer screening. Among the assays measuring HPV DNA, polymerase chain reaction (PCR)-based testing is the current research reference standard because it is highly sensitive and detects a large number of different HPV types. However, the extremely sensitive PCR-based testing may result in undesirable non-specificity in the context of cervical cancer screening, because many young, sexually active normal women harbor low-level, transient HPV infections. Therefore, other methods have been developed for clinical diagnostic use. In the U.S., the leading HPV diagnostic assay is the Hybrid Capture Tube test (HCT), an FDA- approved signal-amplification test that captures and detects target HPV DNA, bound by RNA probes, using antibodies directed against the DNA-RNA hybrids. To evaluate the performance of HCT as well as the MY09-MY11 PCR-based method, we analyzed HPVD-NA test data from our cohort of nearly 23,800 women in Portland, Oregon. Among the 596 samples tested by both PCR and HCT, agreement on overall HPV positivity (any type) was 93%. Using PCR as the reference standard, the sensitivity of HCT was higher for samples obtained from women diagnosed with concurrent squamous intraepithelial lesions (SIL) (81%) than for those collected from women with normal cytology (47%). Quantitative HCT results revealed a higher load of HPV infection among infected women with SIL (mean = 543.2 pg/ml, 95% CI 365.7-720.7) than those with normal cytology (mean = 243.9 pg/ml, 95% CI 95.9-391.9). In another larger subset of women tested by either assay, the individual performances of HCT and PCR were again more equivalent among women with concurrent SIL than among cytologically normal women. Overall, a higher proportion of women who tested HPV-positive by HCT were found to have concurrent SIL, compared to that of women who tested positive by PCR. On the other hand, women who tested HPV-negative by PCR were less likely to have concurrent or incipient (develop into SIL in a few months) SIL than those tested negative by HCT. Digene Corporation has recently modified HCT by introducing a new microplate format (HC II) and by lowering the detection threshold from the original 10 pg/ml to 1 pg/ml (or even lower) to increase analytical sensitivity of HPV detection. The new HC II kits should be carefully evaluated, along with recently developed PCR diagnostic kits, to determine the most suitable uses of these modified assays in different clinical settings.