title: Human papillomavirus (HPV) testing in the management of women with abnormal Pap smears. Experience of a colposcopy referral clinic.
abstract: OBJECTIVE
  Several detailed algorithms for the appropriate use of human papillomavirus (HPV) testing in the management of women with abnormal Pap (Papanicolaou) smears have been launched, but their direct country-to-country adoption is difficult. This necessitates their testing in individual settings, which is ongoing in our colposcopy referral clinic.
  
  
  METHODS
  A series of 224 consecutive women attending the clinic with the usual referral indications (ASC-US or higher in Pap) were examined by the conventional diagnostic tools (PAP smear, colposcopy, punch biopsy) and subjected to HPV testing and viral typing for both low-risk (L-R) and high-risk (H-R) types by nested PCR-based techniques. Predictors of the high-grade diagnostic categories were analysed using both univariate- and multivariate modelling, and the performance characteristics (sensitivity, specificity, NPV, PPV) of all tests in detecting high-grade CIN were calculated.
  
  
  RESULTS
  In the PAP test, ASC-US smears were most common (37.9%), followed by low-grade squamous intraepithelial lesions (LSIL) (26.3%) and high-grade SIL (HSIL) (4.9%). Colposcopy was performed for 180 women, of whom 48.3% had a normal transformation zone (TZ), 40.6% had ATZ1 (abnormal TZ grade 1), and 5.6% had ATZ2. In biopsy (n = 71), 49.3% had CIN1, 5.6% CIN2, and 16.9% CIN3. The HPV test was positive in 64 (28.8%) women, more often in those aged < 35 years (p = 0.025). High-grade colposcopy (ATZ2) was significantly associated with HSIL in the Pap test (OR 20.5; 95% CI: 4.34-96.47), and with HPV test positivity (OR 6.37; 95% CI: 1.58-25.73). The most significant predictors of CIN3 were HSIL in the PAP, HPV test positivity, and high-grade colposcopy. HSIL and HPV test (for H-R types), but not colposcopy, retained their significance as independent predictors of CIN3 also in adjusted multivariate models: OR 88.27; 95% CI 4.17-1867.04, and OR 19.46; 95% CI 2.01-187.75, for the HSIL and H-R HPV test, respectively. Changing the cut-off level of the Pap test from ASC-US to HSIL increased the specificity of the test up to 96.4%, with the loss in sensitivity from 87.5% to 43.8%. Colposcopy (ATZ2) had 92% specificity, and NPV competing with that of the Pap test. The sensitivity of HPV test exceeds that of the Pap test at HSIL cut-off level, but the specificity of the PAP test is clearly superior.
  
  
  CONCLUSIONS
  Accurate predictors of significant cervical pathology (CIN3) are well defined, but the problem is the different performance of the diagnostic tools in clinical practice. A proficient combination of the tests is likely to result in the most satisfactory clinical practice in the management of women with abnormal Pap tests (MAPS).
authors.affiliation: Laboratory of Clinical Microbiology and Virology, University Hospital Policlinico Tor Vergata (Italy).
authors.forename: M
authors.initials: M
authors.lastname: Ciotti
authors.forename: F
authors.initials: F
authors.lastname: Sesti
authors.forename: P
authors.initials: P
authors.lastname: Paba
authors.forename: A
authors.initials: A
authors.lastname: Benedetto
authors.forename: L
authors.initials: L
authors.lastname: Patrizi
authors.forename: A
authors.initials: A
authors.lastname: Criscuolo
authors.forename: E
authors.initials: E
authors.lastname: Piccione
authors.forename: M
authors.initials: M
authors.lastname: Branca
authors.forename: K
authors.initials: K
authors.lastname: Syrjänen
authors.forename: C
authors.initials: C
authors.lastname: Favalli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000554:Ambulatory Care Facilities; D003127:Colposcopy / Q000379:methods*; D017931:DNA Primers; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012017:Referral and Consultation; D012680:Sensitivity and Specificity; D014412:Tumor Virus Infections / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology; D014626:Vaginal Smears / Q000379:methods*; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology
chemical_list: D017931:DNA Primers; D004279:DNA, Viral