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

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 CIN3þ 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 CIN3þ without and with knowledge of HPV positivity were estimated. Findings: A total of 4087 women were included, of which 490 had histologically confirmed CIN3þ (455 CIN3 and 35 cancers). Cytology sensitivity without knowledge of HPV positivity for CIN3þ was 47.2% (95% CI ¼ 42.5 to 51.9), whereas with knowledge of HPV positivity, the sensitivity was higher (58.9%, 95% CI ¼ 54.2 to 63.5; P<.0001). The specificity without knowledge of HPV was 89.4% (95% CI ¼ 88.2 to 90.5), whereas with knowledge of HPV positivity was 78.9% (95% CI ¼ 77.4 to 80.4; P<.0001). Performance estimates varied by study center for cytology without knowing the HPV positivity (range ¼ 32.8%-61.5% for sensitivity; range ¼ 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.