title: Viral load of high-risk human papillomaviruses as reliable clinical predictor for the presence of cervical lesions.
abstract: BACKGROUND
  Infections with high-risk human papillomaviruses (Hr-HPV) can cause malignant transformation of the human cervical epithelium. HPV DNA tests generally are very sensitive to detect cervical neoplastic lesions but also identify transient HPV infections. As a consequence, the specificity and positive predictive value are low.
  
  
  METHODS
  We analyzed viral load of Hr- and possibly Hr-HPV types more than seven orders of magnitude (on a log10 scale) in 999 consecutive BD-SurePath liquid-based cervical cytology samples from routine cervical screening enriched with atypical squamous cells of undetermined significance (n = 100), low-grade squamous intraepithelial lesions (LSIL; n = 100), and high-grade squamous intraepithelial lesions (HSIL; n = 97) using type-specific multiplex quantitative real-time PCR and the BSGP5+/6+-PCR/MPG assay. In the 36-month follow-up, 79 histologically verified CIN2+ and 797 double-negative cytology cases were identified.
  
  
  RESULTS
  Viral loads in LSIL and HSIL were significantly increased compared with no intraepithelial lesion or malignancy in both the quantitative PCR (qPCR) and BSGP5+/6+-PCR/MPG assay (P < 0.0001). The mean viral loads in LSIL and HSIL were not significantly different. Using a newly determined high viral load cut off for 14 Hr-HPV types, the sensitivity for prevalent CIN3+ remained at 100% for both assays compared with the minimal detection threshold. The specificity (corresponding to double-negative cytology at subsequent screening episodes) increased substantially (qPCR, from 91.1% to 95.7%; BSGP5+/6+-PCR/MPG, from 79.8% to 96.2%).
  
  
  CONCLUSIONS
  Compared with DNA positivity alone, high Hr-HPV viral loads could reduce the amount of false positive results detected by the BSGP5+/6+-PCR/MPG and qPCR by 81.4% and 52.1%, respectively.
  
  
  CONCLUSIONS
  Quantitative type-specific HPV DNA assays show high flexibility in defining thresholds that allow optimizing clinical accuracy for cervical cancer precursors.
authors: Corresponding Author: Markus Schmitt, German Cancer Research Center (DKFZ), INF 242, Heidelberg 69120, Germany. markus.schmitt@dkfz.de
authors: Markus
authors: M
authors: Schmitt
authors: Christophe
authors: C
authors: Depuydt
authors: Ina
authors: I
authors: Benoy
authors: Johannes
authors: J
authors: Bogers
authors: Jerome
authors: J
authors: Antoine
authors: Michael
authors: M
authors: Pawlita
authors: Marc
authors: M
authors: Arbyn
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology*; D011379:Prognosis; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D019562:Viral Load / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000821:virology*
chemical_list: D004279:DNA, Viral