HPV detection and measurement of HPV-16, telomerase, and survivin transcripts in colposcopy clinic patients.
OBJECTIVE
To determine whether the detection of high risk human papillomavirus (HPV) types is more predictive for high grade CIN than the current cervical smear test, and whether the production and measurement of HPV type 16 (HPV-16) and cellular survivin and telomerase transcripts can be used to discriminate between cervical HPV infections that self cure and those that induce high grade lesions.


METHODS
Three hundred and fifty four cervical smear samples from women attending the colposcopy clinic were tested by the polymerase chain reaction (PCR) for the presence of HPV. Transcripts for HPV-16 E6, E6*I, E6*II, E7, and L1 as well as cellular survivin, telomerase RNA component, and telomerase reverse transcriptase were measured using fluorogenic probe (Taqman) assays.


RESULTS
Referral smear grades of severe or moderate showed greater positive predictive values for CIN 2/3 than did the detection of high or moderate risk HPV types. HPV-16 transcripts from E6, E6*I, E6*II, and E7 showed high predictive values for CIN 2/3, but low sensitivity. The telomerase RNA component was detected in 53 of 57 samples and telomerase reverse transcriptase was only detected in one sample, whereas survivin transcripts were detected in 40% of samples.


CONCLUSIONS
The detection of HPV-16 or cellular survivin or telomerase transcripts did not accurately predict the grade of CIN in the samples. The detection of HPV risk types correlated well with the grade of CIN; however, the referral grade smear was the most accurate predictor of the severity of the lesion. Of the 35 different HPV types detected, 18 are not included in the HPV hybrid capture II commercial test kit. The use of such kits would have missed HPV infection in 4.3% of clinic patients with CIN 2/3 lesions and 15.4% with CIN 0/1.
Lanham
S
S
Department of Molecular Microbiology, Southampton General Hospital, Southampton SO16 6YD, UK. sal3@soton.ac.uk
Herbert
A
A
Watt
P
P
D000328:Adult; D000368:Aged; D002278:Carcinoma in Situ / Q000473:pathology / Q000821:virology*; D002584:Cervix Uteri / Q000201:enzymology / Q000821:virology*; D003127:Colposcopy; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000473:pathology; D011237:Predictive Value of Tests; D011506:Proteins / Q000032:analysis; D011933:Reagent Kits, Diagnostic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D000077022:Survivin; D019098:Telomerase / Q000032:analysis; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000175:diagnosis* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D014626:Vaginal Smears
C107489:BIRC5 protein, human; D004279:DNA, Viral; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D011933:Reagent Kits, Diagnostic; D000077022:Survivin; D019098:Telomerase