Effect of cervical cytologic status on the association between human papillomavirus type 16 DNA load and the risk of cervical intraepithelial neoplasia grade 3

Abstract

Background: Although correlations between cervical cytologic status and both human papillomavirus (HPV) load and histopathologic status are recognized, it is largely undetermined whether the association between the HPV DNA load and the risk of cervical intraepithelial neoplasia grade 3 (CIN-3) differs on the basis of cervical cytologic findings.

Methods: Study subjects were 821 women enrolled in the ASCUS-LSIL Triage Study who tested positive for HPV-16 at entry. Women were followed semiannually for 2 years. The baseline HPV-16 load was measured by real-time polymerase chain reaction.

Results: CIN-3 was confirmed in 286 (34.8%) of 821 women during the 2-year follow-up period. The adjusted odds ratio (OR) of the 2-year cumulative risk of CIN-3 was 1.46 (95% confidence interval [CI], 1.29-1.64) per 1 log(10) increase in virus load. The ORs varied from 1.66 (95% CI, 1.16-2.37) for women with normal cytologic findings at enrollment to 0.86 (95% CI, 0.61-1.20) for those with high-grade squamous intraepithelial lesions. Among women with normal cytologic findings at enrollment, the area under the receiver operating characteristic curve for detection of CIN-3 on the basis of the virus load was 0.70 (95% CI, 0.61-0.78).

Conclusion: The HPV-16 DNA load was associated with the risk of developing CIN-3, but the associations varied with cytologic findings at the time of virus load measurement. The clinical usefulness of measuring the HPV-16 load as a means to detect CIN-3 was minimal, even in women with normal cytologic findings.

Figure 1. Normal Q-Q plot of the log₁₀-transformed HPV16 DNA load for women with baseline infection

Observed values are plotted against values expected from a normal distribution. If the sample is from a normal distribution, the points are cluster around a straight line.

Figure 2. Receiver operating characteristic curves of quantitative analysis of baseline HPV16 DNA load for detection of 2-year prevalent CIN3

The area under the ROC curve was 0.63 (95% CI, 0.59-0.67) for the entire group of HPV16-positive women: 0.70 (95% CI, 0.61-0.78) for those with normal cytology at enrollment, 0.62 (95% CI, 0.55-0.69) for those with ASCUS, 0.60 (95% CI, 0.55-0.65) for those with LSIL, and 0.46 (95% CI, 0.38-0.54) for those with HSIL.