Impact of knowledge of human papillomavirus positivity on cervical cytology performance in Latin America

J Natl Cancer Inst. 2025 Apr 1;117(4):644-652. doi: 10.1093/jnci/djae283.

Abstract

Background: Cervical cytology is recommended by the World Health Organization as a triage option in human papillomavirus (HPV)-based cervical cancer screening programs. We assessed the performance of cytology to detect CIN3+ without and with knowledge of HPV positivity.

Methods: Women were screened with cytology and HPV across ESTAMPA study centers in Latin America. Screen-positives were referred to colposcopy with biopsy and treatment as needed. Cytology was initially interpreted without knowing HPV results. A subset of cytologies from HPV-positive women were reinterpreted at the same laboratories, with knowledge of HPV status, blinded to previous cytology and histological diagnosis. Performance indicators for cytology to detect CIN3+ without and with knowledge of HPV positivity were estimated.

Findings: A total of 4087 women were included, of which 490 had histologically confirmed CIN3+ (455 CIN3 and 35 cancers). Cytology sensitivity without knowledge of HPV positivity for CIN3+ was 47.2% (95% CI = 42.5 to 51.9), whereas with knowledge of HPV positivity, the sensitivity was higher (58.9%, 95% CI = 54.2 to 63.5; P < .0001). The specificity without knowledge of HPV was 89.4% (95% CI = 88.2 to 90.5), whereas with knowledge of HPV positivity was 78.9% (95% CI = 77.4 to 80.4; P < .0001). Performance estimates varied by study center for cytology without knowing the HPV positivity (range = 32.8%-61.5% for sensitivity; range = 80.7%-98.6% for specificity). Similarly, performance varied with knowledge of HPV positivity (36.1%-93.4% for sensitivity; 39.6%-98.6% for specificity).

Conclusion: The increase in sensitivity of cytology with HPV knowledge was limited and highly variable, reinforcing the need for alternative triage methods to support cervical cancer elimination goals.

MeSH terms

  • Adult
  • Aged
  • Cervix Uteri* / pathology
  • Cervix Uteri* / virology
  • Colposcopy
  • Early Detection of Cancer* / methods
  • Female
  • Health Knowledge, Attitudes, Practice*
  • Human Papillomavirus Viruses
  • Humans
  • Latin America / epidemiology
  • Middle Aged
  • Papillomaviridae* / isolation & purification
  • Papillomavirus Infections* / complications
  • Papillomavirus Infections* / diagnosis
  • Papillomavirus Infections* / epidemiology
  • Papillomavirus Infections* / virology
  • Sensitivity and Specificity
  • Uterine Cervical Dysplasia* / diagnosis
  • Uterine Cervical Dysplasia* / epidemiology
  • Uterine Cervical Dysplasia* / pathology
  • Uterine Cervical Dysplasia* / virology
  • Uterine Cervical Neoplasms* / diagnosis
  • Uterine Cervical Neoplasms* / epidemiology
  • Uterine Cervical Neoplasms* / pathology
  • Uterine Cervical Neoplasms* / virology
  • Vaginal Smears