Comparison of cytology, HPV DNA testing and HPV 16/18 genotyping alone or combined targeting to the more balanced methodology for cervical cancer screening

Gynecol Oncol. 2016 Jul;142(1):120-127. doi: 10.1016/j.ygyno.2016.04.027. Epub 2016 May 8.


Objectives: The objective of the present study was to identify the most effective cervical cancer screening algorithm incorporating different combinations of cytology, HPV testing and genotyping.

Methods: Women 25-55years old recruited for the "HERMES" (HEllenic Real life Multicentric cErvical Screening) study were screened in terms of cytology and high-risk (hr) HPV testing with HPV 16/18 genotyping. Women positive for cytology or/and hrHPV were referred for colposcopy, biopsy and treatment. Ten screening algorithms based on different combinations of cytology, HPV testing and HPV 16/18 genotyping were investigated in terms of diagnostic accuracy.

Results: Three clusters of algorithms were formed according to the balance between effectiveness and harm caused by screening. The cluster showing the best balance included two algorithms based on co-testing and two based on HPV primary screening with HPV 16/18 genotyping. Among these, hrHPV testing with HPV 16/18 genotyping and reflex cytology (atypical squamous cells of undetermined significance - ASCUS threshold) presented the optimal combination of sensitivity (82.9%) and specificity relative to cytology alone (0.99) with 1.26 false positive rate relative to cytology alone.

Conclusion: HPV testing with HPV 16/18 genotyping, referring HPV 16/18 positive women directly to colposcopy, and hrHPV (non 16/18) positive women to reflex cytology (ASCUS threshold), as a triage method to colposcopy, reflects the best equilibrium between screening effectiveness and harm. Algorithms, based on cytology as initial screening method, on co-testing or HPV primary without genotyping, and on HPV primary with genotyping but without cytology triage, are not supported according to the present analysis.

Keywords: Cervical Intraepithelial Neoplasia; Cervical cancer screening; HPV genotyping; HPV testing; Human papillomavirus; Triage to colposcopy.

MeSH terms

  • Algorithms
  • Cervical Intraepithelial Neoplasia / diagnosis
  • Cervical Intraepithelial Neoplasia / pathology
  • Cervical Intraepithelial Neoplasia / virology
  • DNA, Viral / analysis*
  • DNA, Viral / genetics
  • Datasets as Topic
  • Female
  • Genotype
  • Human papillomavirus 16 / genetics*
  • Human papillomavirus 16 / isolation & purification
  • Human papillomavirus 18 / genetics*
  • Human papillomavirus 18 / isolation & purification
  • Humans
  • Middle Aged
  • Papillomavirus Infections / diagnosis
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology


  • DNA, Viral