Estimating the Human Papillomavirus Genotype Attribution in Screen-detected High-grade Cervical Lesions

Epidemiology. 2019 Jul;30(4):590-596. doi: 10.1097/EDE.0000000000001026.


Background: Genotype attribution in high-grade cervical lesions (CIN3+) can be calculated by the hierarchical or proportional method, but these do not account for the genotype distribution in the general population and cannot assess the number of genotype-specific high-grade cervical lesions (CIN3+).

Methods: We present a statistical method for estimating genotype-specific CIN3+ risks and genotype attribution in CIN3+ from cervical screening samples. A key assumption is that genotype-specific infections in women with multiple infections have independent progression risks. We applied the method to 512 human papillomavirus (HPV)-positive women referred for colposcopy and validated it by laser-capture microscopy-polymerase chain reaction. We also compared performance by simulation.

Results: For endpoint CIN3+, the summed deviation of attributable fractions between the estimated genotype-specific attributable fractions and laser-capture microscopy polymerase chain reaction-based attributable fractions was similar for the three methods: 0.17 for the new method (95% confidence interval [CI] = 0.091, 0.28), 0.19 (95% CI = 0.11, 0.33) for the hierarchical method and 0.15 (95% CI = 0.085, 0.26) for the proportional method. Simulations indicated that the new method outperformed the other methods for endpoint CIN3+ when the number of HPV-positive women was large. Exclusion of HPV16-positive women had only a small effect on the estimated genotype-specific risks, supporting the independence assumption.

Conclusions: Genotype-specific attribution in CIN3+ can be accurately predicted by a model that assumes independence between genotypes with respect to disease progression. The method can be used to monitor HPV vaccine effectiveness for prevention of genotype-specific CIN3+ and to assess disease risk after vaccination.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Early Detection of Cancer
  • Female
  • Genotype*
  • Humans
  • Neoplasm Grading
  • Papillomaviridae / genetics*
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / diagnosis
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / prevention & control
  • Papillomavirus Infections / virology*
  • Papillomavirus Vaccines
  • Risk Assessment
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / prevention & control
  • Uterine Cervical Dysplasia / virology*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / prevention & control
  • Uterine Cervical Neoplasms / virology*


  • Papillomavirus Vaccines