Primary screening for cervical cancer based on high-risk human papillomavirus (HPV) detection and HPV 16 and HPV 18 genotyping, in comparison to cytology

PLoS One. 2015 Mar 20;10(3):e0119755. doi: 10.1371/journal.pone.0119755. eCollection 2015.

Abstract

Objectives: The objective of the present study is to assess the performance of a high-risk human papillomavirus (HR-HPV) DNA test with individual HPV-16/HPV-18 genotyping as a method for primary cervical cancer screening compared with liquid-based cytology (LBC) in a population of Greek women taking part in routine cervical cancer screening.

Methods: The study, conducted by the "HEllenic Real life Multicentric cErvical Screening" (HERMES) study group, involved the recruitment of 4,009 women, aged 25-55, who took part in routine cervical screening at nine Gynecology Departments in Greece. At first visit cervical specimens were collected for LBC and HPV testing using the Roche Cobas 4800 system. Women found positive for either cytology or HPV were referred for colposcopy, whereas women negative for both tests will be retested after three years. The study is ongoing and the results of the first screening round are reported herein.

Results: Valid results for cytology and HPV testing were obtained for 3,993 women. The overall prevalence of HR-HPV was 12.7%, of HPV-16 2.7% and of HPV-18 1.4%. Of those referred for colposcopy, cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was detected in 41 women (1.07%). At the threshold of CIN2+, cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] and HPV testing showed a sensitivity of 53.7% and 100% respectively, without change between age groups. Cytology and HPV testing showed specificity of 96.8% and 90.3% respectively, which was increased in older women (≥30) in comparison to younger ones (25-29). Genotyping for HPV16/18 had similar accuracy to cytology for the detection of CIN2+ (sensitivity: 58.5%; specificity 97.5%) as well as for triage to colposcopy (sensitivity: 58.5% vs 53.7% for cytology).

Conclusion: HPV testing has much better sensitivity than cytology to identify high-grade cervical lesions with slightly lower specificity. HPV testing with individual HPV-16/HPV-18 genotyping could represent a more accurate methodology for primary cervical cancer screening in comparison to liquid-based cytology, especially in older women.

MeSH terms

  • Adult
  • Biopsy
  • Colposcopy
  • Cytological Techniques
  • Early Detection of Cancer
  • Female
  • Genotyping Techniques
  • Human papillomavirus 16 / genetics*
  • Human papillomavirus 18 / genetics*
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / virology*
  • Reproducibility of Results
  • Risk Factors
  • Uterine Cervical Dysplasia / diagnosis
  • Uterine Cervical Dysplasia / etiology
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / etiology*
  • Young Adult

Grants and funding

The cobas HPV test kits and consumables for this study were provided by Roche Diagnostics (http://molecular.roche.com). There were no other funding sources or sources of support. All the necessary work for the study performed by physicians, midwives and technicians was incorporated in their routine daily practice. No additional costs needed to be covered. Roche Diagnostics played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.