Human papilloma virus genotyping for the cross-sectional and longitudinal probability of developing cervical intraepithelial neoplasia grade 2 or more

Int J Cancer. 2018 Jul 15;143(2):333-342. doi: 10.1002/ijc.31326. Epub 2018 Mar 9.


Human papilloma virus (HPV) testing is more sensitive but less specific than cytology. We evaluated stand-alone genotyping as a possible triage method. During a multicentre randomised controlled trial comparing HPV testing to conventional cytology, HPV-positive women were referred to colposcopy and followed up if no high-grade lesion was detected. HPV-positive samples were genotyped by GP5+/GP6+ primed polymerase chain reaction followed by reverse line blot. Genotypes were hierarchically ordered by positive predictive value (PPV) for CIN grade 2 or more (CIN2+), and grouped by cluster analysis into three groups (A, B and C in decreasing order). Receiver operating characteristic curves were computed. Among 2,255 HPV-positive women with genotyping, 239 CIN2+ (including 113 CIN3+) were detected at baseline or during a 3-year follow-up. HPV33 had the highest PPV with CIN2+ and CIN3+ as the endpoint and when considering lesions detected at baseline or also during follow-up. HPV16 and HPV35 were the second and third, respectively. Cross-sectional sensitivity for CIN2+ at baseline was 67.3% (95% CI 59.7-74.2), 91.8% (95% CI 86.6-95.5) and 94.7% (95% CI 90.2-97.6), respectively, when considering as "positive" any of the HPV types in group A (33, 16 and 35), A or B (31, 52, 18, 59 and 58) and A or B or C (39, 51, 56, 45 and 68). The corresponding cross-sectional PPVs for CIN2+ were 15.8% 95% (CI 13.2-18.7), 12.0% (95% CI 10.3-13.9) and 9.6% (95% CI 8.2-11.1), respectively. HPV33, 16 and 35 confer a high probability of CIN2+ but this rapidly decreases when adding other genotypes.

Keywords: HPV; cervical screening; genotyping; triage.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Colposcopy
  • Cross-Sectional Studies
  • Cytodiagnosis
  • DNA, Viral / genetics*
  • Early Detection of Cancer
  • Female
  • Genotype
  • Humans
  • Longitudinal Studies
  • Middle Aged
  • Neoplasm Grading
  • Papillomaviridae / classification*
  • Papillomaviridae / genetics
  • Papillomavirus Infections / diagnosis*
  • Sensitivity and Specificity
  • Uterine Cervical Dysplasia / diagnosis
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology*
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology*


  • DNA, Viral