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Relation between E6/E7 transcripts expression and clinical and viro-immunolgical parameters in HIV/HPV co-infected women

Abstract number: P1180

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

Introduction: HIV infected women have a higher oncogenic risk when infected from HPV. Cancer screening and follow up with conventional cytology or HPV typing need to be revisited due to the high prevalence of mild conditions, the high sensitivity of DNA assays and the different pattern of regression/progression in immunocompromized if compared to immunocompetent people. Factors involved in progression to pre-invasive and invasive lesions are virus and host dependant but, once the HPV genome has integrated in host cell, an over-expression of the HPV E6 and E7 genes can be detected.

Here we want to evaluate the correlation between HPV E6 and E7 expression with clinical and immuno-virological parameters to verify clinical performance of this test in the triage of HIV infected women.

Methods: HIV/HPV co-infected women included in the GISPAP cohort (L Sacco University Hospital, Milan – Italy) have been included in this analysis. Pts have been evaluated with cytology, HPV genotyping, HPV E6/E7 mRNA analysis, colposcopy and biopsy of suspected lesions; CDC stage of HIV infection, HIV RNA, CD4 and antiretroviral treatments were collected from clinical records of the patients.

Results: Among 150 HIV/HPV co-infected women included in this analysis, 209 high and low risk HPV genotypes were identified, HPV-52, 16 and 66 being the most represented. Pap smears were neg for cytological lesions in 81 patients, ASC in 3 pts, LSIL in 48 pts and HSIL in 12 pts, unavailable in 6 pts. Colposcopic evaluation in 61 pts revealed 21 abnormal patterns. Biopsies performed in 18 pts revealed 3 CIN-1, 5 CIN-2, 2 CIN-3 and 8 were neg for intraepithelial lesions.

E6/E7 test was positive in 68 (45.33%) of the cases. In a univariate logistic regression model, HR genotypes, LSIL or HSIL, ANTZ1–2, CD4 <200 and multi-experienced for antiretroviral treatment patients, are strongly related to HPV E6/E7 mRNA expression (tab 1).

Discussion: E6/E7 mRNA expression is highly predictive of HPV related lesions in HIV infected women. However, in severely immunosuppressed patients and antiretroviral multiexperienced patients the odds ratio of a positive result for mRNA transcripts is 8 and 4 timer higher respectively, thus suggesting an important role of host interaction in promoting HPV integrated onchogenic evolution.

Table 1. Clinical and immuno-virological parameters and odds ratio of HPV E6/E7 positive results

VariableE6/E7 mRNA (N pos/N neg)Fisher's exact testOR95% CI
CDC stage (78 pts)    
  A6/9 1 
  B17/200.761.270.38 to 4.31
  C16/100.212.400.65 to 8.81
CD4 (138 pts)    
  >50014/28 1 
  200–50037/440.24711.6820.7736 to 3.656
  <20012/30.00258.0001.936 to 33.06
HIV RNA (138 pts)    
  <5044/58   
  50–5007/40.21862.3070.6351 to 8.378
  >50012/130.48101.8960.4412 to 8.147
TARV (141 pts)    
  No6/8 1 
  Yes59/681.00001.1570.3795 to 3.527
ARV regimen experienced (81 pts)    
  06/8 1 
  1–210/60.46422.2220.5136 to 9.616
  3–56/101.00000.80000.1849 to 3.462
  >522/60.03624.8891.216 to 19.66
HPV genotypes (204 genotypes)    
  LR30/41 1 
  HR81/540.01862.0501.144 to 3.674
Cytology (144 pts)    
  NEG/inadequate25/56 1 
  ASC1/21.00001.1200.09695 to 12.94
  LSIL31/170.00024.0851.917 to 8.704
  HSIL9/30.00746.7201.675 to 26.96
Colposcopy (61 pts)    
  NTZ11/29 1 
  ANTZ110/40.00916.5911.706 to 25.47
  ANTZ27/00.000538.482.027 to 730.3
Biopsy (18 pts)    
  Neg4/4 1 
  CIN 1–2–38/00.076917.000.7373 to 392.0
Other STI* (81 pts)    
  Yes38/36 1 
  No2/50.43210.37890.06906 to 2.079
*STI: 1 HSV, 4 candida, 2 bacterial vaginosis. Boldface type indicates statistically significant results.

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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