The recognition of high-risk human papillomaviruses (HPVs) as etiological agents of cervical cancer has increased the demands to use testing for HPV for the detection of abnormal cervical smears and for cervical cancer screening. The present study compared the performance of the Hybrid Capture 2 (HC2) assay with that of PCR for the detection of significant cervical lesions in 1,511 women with different risks for HPV infections in three New Independent States of the former Soviet Union. The results showed that the level of agreement between the HC2 assay and PCR was substantial, with a kappa (Cohen) value of 0.669 (95% confidence interval [CI], 0.629 to 0.709). Of the 228 samples with discrepant results, 92 were positive by the HC2 assay but negative by PCR, whereas 136 samples were PCR positive but HC2 assay negative. The positive predictive values (PPVs) of the HC2 assay and PCR in detecting high-grade intraepithelial lesions (HSILs) were 4.5% (95% CI, 3.5 to 5.5%) and 3.6% (95% CI, 2.7 to 4.5%), respectively, and the negative predictive values (NPVs) were 99.6% (95% CI, 99.3 to 99.9%) and 99.3% (95% CI, 98.9 to 99.7%), respectively. The sensitivities of the HC2 assay and PCR for the detection of HSILs were 85.2 and 74.0%, respectively, and the specificities were 67.2 and 64.1%, respectively. In receiver operating characteristic (ROC) analysis, the performance of the HC2 assay for the detection of HSILs was excellent (P ؍ 0.0001); the area under the ROC analysis curve was 0.858 (95% CI, 0.811 to 0.905), and the optimal balance between sensitivity (86.5%) and specificity (80%) was obtained with an HC2 assay cutoff level of 15.6 relative light units/positive control. Use of this cutoff would increase the specificity of the HC2 assay to 80.0% without compromising sensitivity. In conclusion, the results of PCR and the HC2 assay were concordant for 85% of samples, resulting in substantial reproducibility. Both tests had low PPVs, equal specificities, and equal (almost 100%) NPVs for the detection of HSILs; but the sensitivity of the HC2 assay was slightly better.Cervical carcinoma is the second most common malignancy in women worldwide. Infection with high-risk (HR) types of human papillomaviruses (HPVs) is the single most important risk factor for cervical cancer and its precursors (27,29). Screening for cervical cancer is traditionally based on Pap smear cytology, which suffers from subjectivity and which depends on the skills of the observer. The Pap test usually shows variable (poor to moderate) sensitivities (30 to 87%), and equivocal cases need to be repeated to improve diagnostics (4, 13). The recognition of HR HPVs as etiological agents of cervical cancer has increased the demands to use testing for HPV for the diagnosis of abnormal cervical smears (11) and even for screening for cervical cancer (9, 18). Testing for HPV has been shown to have higher sensitivities (84 to 100%) than the conventional Pap smear. Also, the negative predictive value (NPV) of testing for HPV DNA is very high; Clavel et al.(1) rep...
Recently, conflicting results on human papillomavirus (HPV) clearance have been reported and the data on the accumulation of incident HPV infections are still fragmentary. Thus, we completed an analysis of the age-specific incidence and clearance rates of high-risk (HR) HPV infections in 448 women participating in a multi-centre screening study in three New Independent States countries. At baseline, 239 of the 448 women were negative for HR HPV DNA, whereas 209 were HR HPV-positive and cleared HR HPV during the prospective follow-up. The cumulative incidence and clearance of HR HPV were modelled using life-table techniques. The monthly incidence rates of HR HPV were significantly age dependent (p = 0.0001), whereas monthly clearance rates remained constant across the nine age groups (p = 0.920). The incidence rates (3.04% and 2.65%) exceeded the clearance rates in the two youngest age groups only, 15-20- and 21-25-year-old women, and remained lower (0-0.84%) in all other age groups. The cumulative rate of incident HR HPV infections (1.0%) was significantly lower than the overall clearance rate (1.9%) (p = 0.001). In life-table analysis, incident HR HPV infections between the nine age groups were significantly different (p = 0.0001), while cumulative HR HPV clearance was identical in all groups (p = 0.822). The accumulation of incident HR HPV infections is significantly age-related, whereas virus clearance remains constant between 15 and 60 years of age. These distinct age-specific incidence and clearance rates explain the differences in age-specific prevalence of HR HPV infections in the study population.
These data indicate that cigarette smoking is not an independent risk factor of CIN2+, but the increased risk ascribed to smoking is mediated by acquisition of HR-HPV, of which current smoking was an independent predictor in multivariate model.
The rates of acquisition and the times of incident high-risk (HR) human papillomavirus (HPV) infectionsand Pap smear abnormalities and their predictive factors were analyzed in women participating in a multicenter screening study in three countries of the New Independent States of the former Soviet Union. The 423 patients were prospectively monitored for a mean of 21.6 months. At the baseline, 118 women were HR HPV DNA negative (Hybrid Capture II assay) and Pap smear negative (group 1), 184 were HPV DNA positive and Pap smear negative (group 2), and 121 were HPV DNA negative and Pap smear positive (group 3). The time to the acquisition of an incident abnormal Pap smear (19.4 months) was significantly longer in group 1 than in group 2 (9.2 months) (P ؍ 0.0001). The times of acquisition of incident HR HPV infection were 16.6 and 11.0 months in group 1 and group 3, respectively (P ؍ 0.006). The monthly rates of acquisition of incident HR HPV infections were very similar in group 1 (1.0%) and group 3 (0.8%), whereas the rate of acquisition of an abnormal Pap smear was significantly higher in group 2 (3.1%) than in group 1 (1.5%) (P ؍ 0.0001). The acquisition of HR HPV infection (but not a positive Pap smear result) was significantly (P ؍ 0.0001) age dependent. The only significant independent (P ؍ 0.001) predictor of the incidence of an abnormal Pap smear result was a high HR HPV load of >20 relative light units/control value (CO) (rate ratio, 2.050; 95% confidence interval, 1.343 to 3.129). Independent predictors of incident HR HPV infection were patient category (a sexually transmitted disease) and ever having been pregnant. The time of acquisition of HR HPV infection was 3 months shorter than that of an abnormal Pap smear. At the baseline the high load of a particular HR HPV type is the single most important predictor of an incident Pap smear abnormality, whereas young age and having a sexually transmitted disease predict incident HR HPV infections.The accumulated data from prospective follow-up studies suggest that the natural history of clinical human papillomavirus (HPV) infections of the uterine cervix is basically identical to that of cervical intraepithelial neoplasia (CIN) lesions, with (i) progression, (ii) persistence, and (iii) regression as the main outcome measures (7,13,23). However, special features of the natural history of HPV infections seem to be intimately linked to different risks of the development of cervical cancer (7,22,30,31). These include the presence of latent and subclinical HPV infections and the propensity of the virus to remain persistent (latent) for prolonged periods or to become reactivated or for the infection to undergo spontaneous resolution (3,7,22,30,31).This HPV involvement forms the biological basis of additional patterns recently described in studies of the natural history of CIN lesions, called early regression, fluctuation, and late regression (3,20,21,23,24). It seems obvious that the HPV type, viral load, the acquisition of new (incident) infections, as wel...
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