p300 expression is related to high-risk human papillomavirus infections and severity of cervical intraepithelial neoplasia but not to viral or disease outcomes in a longitudinal setting.

To evaluate the role of the expression of the transcription factor p300 as an independent predictor of high-risk human papillomavirus (HR-HPV) infections and outcome of the cervical disease.Cervical biopsy samples taken at enrolment from 225 women of the Latin American Screening study cohort were analyzed for p300 using immunohistochemistry to assess its value as predictor of (a) cervical intraepithelial neoplasia (CIN) grade, and (b) HR-HPV at baseline, as well as (c) outcomes of HR-HPV infections, and (d) development of incident CIN as surrogate endpoints of progressive disease.There was a significant linear trend in increasing upregulation (=pattern shift) of p300 (P=0.0001) in parallel with increasing grade of CIN. When dichotomized (normal/moderately increase vs. strong-intense), upregulated p300 expression predicted CIN3+ with odds ratio=4.16 (95% confidence interval: 1.95-8.86) (P=0.0001) and CIN2+ with odds ratio=3.48 (95% confidence interval: 1.86-6.48) (P=0.0001). p300 was upregulated more often in HR-HPV+ lesions than in those remaining negative. Semiquantitative viral loads were also directly related to upregulation of p300 (P=0.036), but p300 was not a significant predictor of disease progression to either CIN1+ or CIN2+.p300 expression was upregulated in CIN lesions and related to detection and viral load of HR-HPV but not to their outcome or to incident CIN.

Screening for cervical cancer in high-risk populations: DNA pap test or Hybrid Capture II test alone?

This study was designed to evaluate whether Hybrid Capture II (HC2) test alone refer women to colposcopy as appropriately as DNA Papanicolaou (Pap) test, in the context of a high-risk group of women using the recently validated DNACitoliq LBC system. Women with suspected cervical disease were included in this cross-sectional study at a tertiary center in São Paulo, Brazil, for further workup. All women had cervical material collected for LBC and HC2 for high-risk human papillomavirus (hrHPV)-DNA test. Irrespective of cytology and HC2 results, colposcopy, and cervical biopsy when applicable, was systematically performed. All tests were performed blindly. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of both methods were computed in relation to histology. A total of 1,080 women were included: 36.4% (393/1080) had ACUS+, 10.2% (110/1080) were high-grade squamous intraepithelial lesions (HSIL) or cancer. Mean age was 33.5 years. All women underwent colposcopy, and cervical biopsies were performed in 38.4% (415/1080): 33% (137/415) of the biopsies were negative, 14.4% (155/415) were low-grade squamous intraepithelial lesions (LSIL), 10.7% (116/415) were HSIL, and 0.6% (7/415) were cancer. HC2 sensitivity to diagnose biopsy-proven HSIL was 100%. Because all HSIL cases had a positive HC2 test, sensitivity could not be improved by adding LBC. Specificity and positive and negative predictive values of DNA Pap were not significantly different from HC2 test alone when considering LSIL+ histology as "gold standard" and HSIL+ histology. As a screening strategy for women with high-risk for cervical cancer, DNA Pap test does not seem to add substantially to HC2 alone in terms of appropriately referring to colposcopy.

DCS liquid-based system is more effective than conventional smears to diagnosis of cervical lesions: study in high-risk population with biopsy-based confirmation.

OBJECTIVE: To compare the performances of Papanicolaou test (PapTest) and of a new liquid-based cytology method, DNA-Citoliq System (DCS), in a high-risk population, with histology confirmation. METHODS: Paired specimens of exfoliated cervical cells were collected under split-sample protocol. All patients were submitted to colposcopy and a biopsy taken when any atypical transformation zone was seen. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of both conventional and DCS methods were computed in relation to histology. RESULTS: A total of 1095 patients were analyzed by two cytology methods and, in 425 (38.8%), histologically. There were significantly more adequate samples with DCS (98.63%) than with conventional (89.6%) smears (P < 0.001). ASCUS was diagnosed significantly more with DCS than with conventional Pap (P < 0.001). Conventional Pap misclassified as normal 55.4% (158/285) of cases with either LSIL or HSIL or cancer at histology, whereas DCS misclassified 31.2% (89/285) of cases (P < 0.001). DCS had a significantly higher sensitivity (70% and 91.3%) than the conventional Pap (49.8% and 72.8%) to detect both LSIL+ and HSIL+ at histology, respectively. On the other hand, specificity of conventional smear (88.2% and 85.2%) was significantly higher than DCS (75.4% and 70.9%) considering both LSIL+ and HSIL+ at histology, respectively. CONCLUSIONS: This study confirms the superiority of the liquid-based cytology system DCS to detect cervical lesions. The rate of adequate DSC slides was significantly higher than with conventional cytology.

Hybrid capture II and polymerase chain reaction for identifying HPV infections in samples collected in a new collection medium: a comparison.

OBJECTIVE: To compare the performance of human papillomavirus (HPV) DNA detection by polymerase chain reaction (PCR) and Hybrid Capture II (HCII) test (Digene, Gaithersburg, Maryland, U.S.A.) in residual cells left in the collection vials of the DNACitoliq system (Digene Brasil, São Paulo, Brazil). STUDY DESIGN: A series of 263 cervical samples collected for liquid-based cytology with the DNACitoliq system was tested for oncogenic HPV types first with HCII and subsequently with PCR. After DNA purification with GFX Genomic Blood DNA Purification Kit (Amersham, Piscataway, New Jersey, U.S.A.), PCR was performed using AmpliTaq Gold DNA polymerase (Applied Biosystems). PGMY09/11 L1 consensus primers and GH20/PCO4 primers for human beta-globin target were coamplified. RESULTS: Altogether, 260 samples were positive for beta-globin, and 3 negative ones were excluded from the analysis. PCR and HCII yielded concordant results in 199 cases (76.5%) (102 positive and 97 negative), with Cohen's kappa of .577 (95% CI .477-.677) and weighted kappa of .733 (95% CI .659-.791). HPV prevalence in different categories of cytologic abnormalities was practically identical with HCII and PCR assays (P=.989). Among the 61 (23.5%) discrepant cases, 28 samples were HCII+/PCR- cases. Of these, 27 of 28 samples showed a low viral load, and 1 had an intermediate viral load. CONCLUSION: The data suggest that residual material from the DNACitoliq system adequately preserves HPV DNA for detection by HCII and PCR, with performance similar to that of specimen transport medium.