Arianis Tatiana Ramírez

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 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.

Comparison of Hybribio-H13 and Hybrid Capture® 2 human papillomavirus tests for detection of CIN2+ and CIN3+

Introduction. Low-cost, accurate high-risk HPV tests are needed for cervical cancer screening in limited-resource settings.Objective. To compare the performance of the low-cost Hybribio-H13 test with the Hybrid Capture® 2 to detect cervical intraepithelial neoplasia grade 2 or 3 (CIN2 and CIN3).Materials and methods. Archived baseline samples tested by the Hybrid Capture® 2 from women of the ASCUS-COL trial, aged 20 to 69 years, with biopsy-colposcopy directed diagnosis of CIN2+ (n = 143), CIN3+ (n = 51), and < CIN2 (n = 632) were blindly tested by the Hybribio-H13 test.Results. The relative sensitivity of the Hybribio-H13 test versus the Hybrid Capture® 2 for detecting CIN2+ was 0.89 (90% CI = 0,80-0,98; NIT = 0,66), and for CIN3+ was 0,92 (90% CI = 0,85-0,98; NIT = 0,35). Relative specificity was 1.19 (90% CI = 1.05-1.33; NIT <0.00001). In the analysis restricted to women older than 30 years, the relative sensitivity of the Hybribio-H13 for CIN3+ was marginally below unity (ratio = 0.97; 90% CI = 0.95-0.99), and the specificity remained higher than the Hybrid Capture® 2 test.Conclusion. The Hybribio-H13 test was as specific as the Hybrid Capture® 2 for detecting CIN2+ or CIN3+ but less sensitive. Considering these results and the young age of the population recruited for screening because of ASCUS cytology, we suggest our results warrant the evaluation of the Hybribio-H13 for screening cervical cancer, especially in the evaluated population.

Reflections Regarding Validation of New HPV Tests With Reduced HPV Genotypes: Report From an IARC Expert Consultation

ABSTRACT Of the 12 HPV genotypes classified as carcinogenic to humans (Group 1), over 95% of HPV‐positive cervical cancers are linked to eight genotypes (HPV16/18/31/33/35/45/52/58). Screening programmes may consider HPV tests incorporating only these genotypes to improve screening efficiency and reduce programmatic costs. Validation of such tests requires fine‐tuning of existing criteria. An expert group convened by the International Agency for Research on Cancer discussed how existing criteria by Meijer et al. for HPV screening clinical validation should be adapted to evaluate new reduced‐valency HPV tests. Experts identified four key criteria: (1) Clinical performance criteria should meet WHO HPV test Target Product Profiles (TPP) minimal standards with high relative sensitivity ( ≥ 0.90 for CIN2+ and ≥ 0.95 for CIN3+) and relative specificity ( ≥ 0.98 for ≤ CIN1) to detect CIN2/3+ lesions associated with types targeted by the test, as established by a comparator test providing information on the presence of the targeted genotypes; (2) Comparator tests should be clinically validated according to Meijer criteria principles for comparator tests, and should offer HPV genotyping to detect at least the types included in the reduced‐valency test; (3) Cervical samples should be representative of a population‐based screening programme; (4) Intra‐ and inter‐laboratory reproducibility should adhere to Meijer criteria and, preferentially also the more stringent TPP. As the global HPV type distribution in cervical cancer is well known, a future evaluation strategy may consider including both virological and simplified clinical standards. The consultation highlights essential criteria building on existing clinical accuracy standards, enriched with analytical standards. These criteria will be instrumental in ensuring both accuracy and reliability of new reduced‐valency HPV tests for cervical cancer screening highly needed to assure 70% coverage aim of cervical cancer elimination.