Is Human Papillomavirus Viral Load a Clinically Useful Predictive Marker? A Longitudinal Study

Abstract

Background: It has been suggested that in women who test positive for high-risk human papillomavirus (HPV) types, viral load can distinguish women who are at increased risk of cervical neoplasia from those who are not.Methods: Quantitative PCR (qPCR) was used to measure HPV copy number in serial samples taken from 60 and 58 young women previously found to have incident cervical HPV16 or HPV18 infections, respectively, using GP5+/GP6+ primers; women provided at least three samples for qPCR testing, at least one of which was positive.Results: A 10-fold increase in HPV16 or HPV18 copy number was associated with a modestly increased risk of acquiring a cytologic abnormality [HPV16: hazards ratio, 1.76 (95% confidence interval, 1.38-2.25); HPV18: hazards ratio, 1.59 (95% confidence interval, 1.25-2.03)]. However, in most women, copy number increased during follow-up, before decreasing again. In women with a HPV16 infection, the median copy number per 1,000 cells was 7.7 in their first qPCR HPV-positive sample, 1,237 in the sample yielding the maximum copy number, and 7.8 in their last qPCR HPV-positive sample; corresponding copy numbers for women with HPV18 infection were 2.3, 87, and 2.4. Maximum HPV16 and HPV18 copy number did not differ significantly between women who acquired an incident cervical cytologic abnormality and those who did not.Conclusion: Whereas large relative increases in copy number are associated with an increased risk of abnormality, a single measurement of viral load made at an indeterminate point during the natural history of HPV infection does not reliably predict the risk of acquiring cervical neoplasia. Therefore, a single measure of HPV viral load cannot be considered a clinically useful biomarker. Cancer Epidemiol Biomarkers Prev; 19(3);

Comparison of Abbott RealTime High Risk HPV and Hybrid Capture 2 for the detection of high-risk HPV DNA in a referral population setting

“…However the association between viral load and disease severity is still matter of debate. 17 Analysis of samples with discordant results between ART and HC2 in our study revealed cross reactivity of HC2 with non-targeted HPV types in 12 cases, while only 2 cases were found with ART. These findings confirm observations from numerous previously studies 18 and demonstrate superior analytical performance of ART.…”

Clinical Validation of a Type-Specific Real-Time Quantitative Human Papillomavirus PCR against the Performance of Hybrid Capture 2 for the Purpose of Cervical Cancer Screening

“…And finally, we recommend the use of individual type-specific and normalized (for the number of cells) HPV tests which allow monitoring of individual patients over time (12). Such serial measurements without clinical threshold constraints (9,12,16), in comparison to a fixed single viral load threshold (24,25), could allow earlier detection of CIN2ϩ and improve clinical sensitivity.…”

Detection of human papillomavirus (HPV) L1 gene DNA possibly bound to particulate aluminum adjuvant in the HPV vaccine Gardasil®

“…Existent enzyme-based biochemical methods cannot quantify the DNA bound to a particulate aluminum adjuvant. Quantitation of HPV by qPCR assay involves phenol/chloroform extraction of the HPV DNA from proteinase K digestate [46].Such assays cannot be used to quantify the mineral-bound DNA which requires a nested PCR with a highly processive DNA polymerase for detection.…”