CINtec PLUS and cobas HPV testing for triaging Canadian women referred to colposcopy with a history of low-grade squamous intraepithelial lesion: Baseline findings

Abstract

Objective and methods CINtec PLUS and cobas HPV tests were assessed for triaging women referred to colposcopy with a history of LSIL cytology. Both tests were performed at baseline using ThinPrep cervical specimens and biopsy confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) served as the clinical endpoint. Results In all ages, (19–76 years, n = 600), 44.3% (266/600) tested CINtec PLUS positive vs. 55.2% (331/600) HPV positive (p = 0.000). Based on 224 having biopsies, sensitivity to detect CIN2+ (n = 54) was 81.5% (44/54) for CINtec PLUS vs. 94.4% (51/54) for HPV testing (p = 0.039); specificities were, 52.4% (89/170) vs. 44.1% (75/170), respectively (p = 0.129). In women ≥30 years (n = 386), 41.2% (159/386) tested CINtec PLUS positive vs. 50.8% (196/386) HPV positive (p = 0.008). Based on 135 having biopsies, sensitivity to detect CIN2+ (n = 24) was 95.8% (23/24) for both CINtec PLUS and HPV tests; specificities were, 55.0% (61/111) vs. 50.5% (56/111), respectively (p = 0.503). Conclusions For women referred to colposcopy with a history of LSIL cytology, CINtec PLUS or cobas HPV test could serve as a predictor of CIN2+ with high sensitivity, particularly in women ≥30 years. Either test can significantly reduce the number of women requiring further investigations and follow up in colposcopy clinics.

Comparison of CINtec PLUS cytology and cobas HPV test for triaging Canadian patients with LSIL cytology referred to colposcopy: A two-year prospective study

“…Age ranged from 19 to 76 years (median, 33.0), with 384 (64.2%) 30 years of age (median, 43.0). (In our baseline paper [ 16 ], the total number of patients with evaluable results was reported as 600. Upon final review, 2 patients were found not to have met study inclusion criteria and removed from our final analysis, resulting in 598 patients in the study.…”

“…For those with LSIL cytology, either direct referral to colposcopy or repeat cytology at 6-month intervals is recommended; for those having persistent atypical squamous cells of undetermined significance (ASCUS) or worse in repeat cytology, colposcopy is recommended [ 1 ]. In colposcopy clinics, all referred patients undergo cytology and colposcopic examination with biopsies of any lesions detected, and further follow-up clinical pathways depend on specific criteria as previously described [ 16 ].…”

“…Statistical analysis was performed using SPSS for Windows, versions 23 and 27, Excel, Microsoft Office Professional Plus, 2013, MedCalc, 2021, and Social Science Statistics website, 2020 initially at baseline, as previously described [ 16 ], and after two-years of prospective follow-up. Qualitative variables were studied through different frequencies.…”

“…CINtec PLUS is a dual-stain immunocytochemical test which detects p16 and Ki-67 proteins that are over expressed in cervical cells with transforming HPV infection. As the expression of p16 and Ki-67 is mutually exclusive in normal cells, the co-detection of these proteins simultaneously within the same cervical epithelial cell serves as a specific marker of HPV-mediated oncogenic transformation and predictor of cervical cancer risk [ 5 , 7 , 8 , 9 , 10 , 16 ]. CINtec PLUS has been shown to be more sensitive than cytology with equal specificity, and more specific than HPV testing with relatively comparable sensitivity for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2 ) in LSILs [ 11 , 17 , 18 , 19 , 20 ].…”

“…The initial study data were obtained at baseline, and the study cohort remaining under care in the colposcopy clinic was followed up to 2 years to ascertain disease outcome. We previously communicated our baseline findings [ 16 ], and in this manuscript, we present the complete data obtained in the study.…”