Edmundo Torres-González

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.

The D2 and D3 Sublineages of Human Papilloma Virus 16–Positive Cervical Cancer in Guatemala Differ in Integration Rate and Age of Diagnosis

Abstract Human papillomavirus (HPV) 16 displays substantial sequence variation; four HPV16 lineages (A, B, C, and D) have been described as well as multiple sublineages. To identify molecular events associated with HPV16 carcinogenesis, we evaluated viral variation, the integration of HPV16, and somatic mutation in 96 cervical cancer samples from Guatemala. A total of 65% (62/96) of the samples had integrated HPV16 sequences and integration was associated with an earlier age of diagnosis and premenopausal disease. HPV16 integration sites were broadly distributed in the genome, but in one tumor, HPV16 integrated into the promoter of the IFN regulatory factor 4 (IRF4) gene, which plays an important role in the regulation of the IFN response to viral infection. The HPV16 D2 and D3 sublineages were found in 23% and 30% of the tumors, respectively, and were significantly associated with adenocarcinoma. D2-positive tumors had a higher rate of integration, earlier age of diagnosis, and a lower rate of somatic mutation, whereas D3-positive tumors were less likely to integrate, had later age of diagnosis, and exhibited a higher rate of somatic mutation. In conclusion, Guatemalan cervical tumors have a high frequency of very high-risk HPV16 D2 and D3 sublineages harboring distinct histology, which may help guide future therapeutic strategies to target the tumor and reduce recurrence. Significance: This study details the biological and molecular properties of the most pathogenic forms of HPV16, the cause of the majority of cervical cancers.