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

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

Arianis Tatiana Ramírez  1 , David Mesher  1   2 , Armando Baena  1 , Yuli Salgado  3 , Elena Kasamatsu  4 , Carmen Cristaldo  4 , Rodrigo Álvarez  5 , Freddy David Rojas  5 , Katherine Ramírez  5 , Julieta Guyot  6 , Odessa Henríquez  7 , Hans González Palma  8 , Bettsy Flores  8 , Jhaquelin Peñaranda  8 , María José Vero  9 , Isabel Robinson  9 , Mary Luz Rol  1 , Guillermo Rodríguez  10 , Carolina Terán  8 , Annabelle Ferrera  11 , María Alejandra Picconi  12 , Alejandro Calderon  5 , Laura Mendoza  4 , Carolina Wiesner  3 , Maribel Almonte  1   13 , Rolando Herrero  1   14 ; ESTAMPA Study Group
Collaborators, Affiliations

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

Arianis Tatiana Ramírez et al. J Natl Cancer Inst. .

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.

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Conflict of interest statement

All authors declare no competing interests.

Figures

Figure 1.
Figure 1.
Study population. ESTAMPA participants recruited between December 2012 and March 2020.
Figure 2.
Figure 2.
Forest plots for the performance of cytology without and with knowledge of HPV positivity for CIN3+ detection at 7 study centers.
See this image and copyright information in PMC

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