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E6/E7 expression in the triage of HIV-HPV co-infected patients

Abstract number: P1181

Orlando G., Beretta R., Agarossi A., Rimoldi S., Antonacci C., Mazza F., Zanchetta N., Pagano F., Fasolo M., Pileri P., Omodeo Zorini E., Casolati E., Gismondo M.R.

Objective: Anal and cervical HPV related infections occur frequently in HIV infected pts and progression to invasive lesions depends both on HPV types and on host immune response. HPV E6/E7 genes are over-expressed in high-grade lesions and cancers as a consequence of HPV integrated cycle. Detection of E6/E7 mRNA could be a specific marker for high-grade disease and cancer.

We want to evaluate the rate of HPV E6/E7 mRNA expression according to cytology, CD4 cells and HIV-RNA in anal and cervical samples in HIV positive persons to define the potential effectiveness of this molecular approach in the primary screening of such pts.

Methods: E6/E7 mRNA expression was assessed by APTIMA® HPV assay (Gen-Probe Inc, San Diego, CA, USA) in 235 (85 anal and 150 cervical) samples of HIV pos Males and Females included in the GISPAP cohort – L Sacco Univ Hosp (Milan-Italy). Cervical and anal cytology was evaluated according to Bethesda system 2001. HIV related immuno-virological data were collected from clinical records.

Results: Diagnoses on cytology were: 85 neg, 5 inadequate, 3 ASC, 109 LSIL, 27 HSIL.

Proportion of E6/E7 expression was 81.48%, 73.39% and 30.95% in HSIL, LSIL, and neg respectively (c2 test p < 0.0001). Decreasing rates of mRNA expression in HSIL, LSIL and neg samples were confirmed when analysed according to site of infection (anal or cervical), HIV RNA and CD4 levels. Severely immunosuppressed pts (CD4 <200/microL) expressed E6/E7 in higher proportions when compared to pts with higher CD4 levels with 75% of E6/E7 expression also in neg samples.

High sensitivity/NPV and low specificity/PPV in identifying HSIL was assessed for any different group analysed (tab 1).

Conclusion: The molecular approach for HPV screening is aimed to reduce over-treatment of low-grade and, often, transient abnormalities by increasing specificity and PPV. Expression of E6/E7 mRNA is generally strongly associated with the severity of histological diagnosis while negative results, when 14 HPV genotypes are targeted, could have a high NPV.

In HIV infected pts we found a very low specificity and PPV of E6/E7 mRNA test in identifying HSIL lesions thus preventing its use as primary screening test to reduce the second level assessment need. The meaning of E6/E7 expression in LSIL or neg samples, could be the sign that the shift toward the integrated cycle has already begun and, added to other screening tools, could identify pts with the highest risk of progressive disease.

Table 1. Sensitivity, specificity, positive and negative predictive values of HPV-mRNA detection in predicting HSIL

 pSensitivity (95% CI)Specificity (95% CI)Positive predictive value (95% CI)Negative predictive value (95% CI)Likelihood ratio
All the patients0.00310.81 (0.62–0.94)0.50 (0.43–0.58)0.20 (0.13–0.29)0.94 (0.88–0.98)1.64
Anal samples0.720.87 (0.59–0.98)0.22 (0.12–0.34)0.21 (0.11–0.33)0.87 (0.62–0.98)1.11
Cervical samples0.06550.75 (0.43–0.94)0.57 (0.48–0.65)0.14 (0.065–0.25)0.96 (0.89–0.99)1.73
Patients with      
  CD4 <200/mL1.00001.00 (0.16–1.00)0.13 (0.02–0.40)0.13 (0.02–0.40)1.00 (0.16–1.00)1.15
  CD4 200–500/mL0.03710.85 (0.54–0.98)0.47 (0.37–0.58)0.18 (0.09–0.30)0.96 (0.85–0.99)1.606
  CD4 > 500/mL0.03850.89 (0.52–0.99)0.49 (0.37–0.61)0.17 (0.08–0.31)0.97 (0.86–0.99)1.73
Patients with      
  HIV viral load <50 copies/mL0.01270.87 (0.59–0.98)0.48 (0.39–0.57)0.16 (0.09–0.26)0.97 (0.89–0.99)1.66
  HIV viral load 50–500 copies/mL0.52861.00 (0.29–1.00)0.31 (0.09–0.61)0.25 (0.05–0.57)1.00 (0.4–1.00)1.44
  HIV viral load >500 copies/mL0.37830.83 (0.36–0.99)0.44 (0.28–0.60)0.18 (0.06–0.37)0.95 (0.74–0.99)1.49
Boldface type indicates statistically significant results. Likelihood ratio defined as sensitivity/(1.0 - specificity).

Session Details

Date: 10/04/2010
Time: 00:00-00:00
Session name: Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Vienna, Austria, 10 - 13 April 2010
Presentation type:
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