TEST:

CINtec® PLUS Cytology

Despite the limitations of our study, it provides a foundation for further research into the long-term benefits and cost-effectiveness of this test. Future studies could explore its potential for integration into national screening programs.

P=N/A; N=500; Not yet recruiting; Sponsor:Lisa Flowers

"Roche...announced today that the World Health Organization (WHO) has included dual-stain cytology testing in its cervical cancer prevention guideline.1 The Roche CINtec® PLUS Cytology test is the only FDA-approved and CE-marked dual-stain test that helps identify human papillomavirus (HPV)-positive individuals who are most at risk of developing cervical precancer and cancer."

We calculated the predictive performance of individual tests (cervical cytology, HPV genotyping, CINtecPlus results, and clinical risk factors) or their combination in the prediction of cervical lesion progression, regression, and persistence; (3) The highest predictive performance for the progression of cervical lesions was achieved by a model comprising a Pap smear suggestive of high-grade squamous intraepithelial lesion (HSIL), the presence of 16/18 HPV strains, a positive p16/Ki67 dual staining result along with the presence of at least three clinical risk factors, which had a sensitivity (Se) of 74.42%, a specificity of 97.92%, an area under the receiver operating curve (AUC) of 0.961, and an accuracy of 90.65%. The prediction of cervical lesion regression or persistence was modest when using individual or combined tests; (4) Multiple testing or new biomarkers should be used to improve HPV-positive patient surveillance, especially for cervical lesion regression or persistence prediction.

The p16 marker (CINtec® PLUS) can be used as a prognostic biomarker and provides clinical usefulness through increased sensitivity (Se) and specificity (Sp) in the triage of women at risk of developing precancerous lesions, compared to cytology that is based on morphology, but has a rather low Se and high Sp, while HPV testing is very sensitive but slightly more specific.

"Roche Diagnostics today announced the release of new guidelines from ASCCP and other members of the Enduring Guidelines for Cervical Cancer Screening and Management Committee that now recognize dual-stain biomarkers as an important technology in helping clinicians triage patients to determine if their human papillomavirus (HPV) infection is transforming into cervical pre-cancer."

Dual stain testing with CINtec PLUS Cytology is acceptable for triage of HPV-positive test results. Risk estimates are portable across different populations.

All three High-grade lesions were in the CINtec® PLUS positive category, suggesting CINtec® PLUS might help risk stratification for HPV-positive NILM women in both HPV16/18 vs. other HPV. Furthermore, CINtec® PLUS might be of help for risk stratification specifically in patients with no prior high-grade lesions.

P=N/A; Active, not recruiting --> Completed

Two women tested positive for HPV16 and hrHPV (non-18); of those one had positive CINtec, and HGSIL cytology, and the other had negative CINtec and ASCH. Conclusion Among women with CIN2 the rate of a positive CINTEC+ test is lower than that of cytology testing, possibly reflecting a difference in the oncogenic potential of CIN2 cases.

P=N/A; N=33000; Active, not recruiting; Sponsor:Maria Sklodowska-Curie National Research Institute of Oncology

Attributable risk of all HR-HPV genotypes targeted by both Anyplex and cobas tests was evident in ⩾CIN2/AIS Testing for these genotypes in HPV primary cervical screening and cytology triage could identify those at increased risk of cervical cancer and also be beneficial in the management of LSIL referral populations.

CINtec PLUS Cytology objectively identifies transforming HPV infections in women with abnormal Pap cytology results and HPV-positive cervical cancer screening results. The high positive predictive value of dual-stained cytology for the presence of high-grade CIN may help reduce unnecessary colposcopy. It can help improve management of women with Pap cytology–negative/HPV+ results.

So far, no studies have been conducted on the value of P16/Ki-67 ICC for CIN2 surveillance. If the study identifies high correlation of P16/Ki-67 ICC to colposcopy, larger studies could be designed to investigate longer-term reassurance for the surveillance of women with untreated CIN2 without colposcopy.

Given the low sensitivity of cytology and the low percentage of HPV16-positive cancers among elderly women, triage via cytology and genotyping is not the best strategy; double staining cytology shows high profiles of sensibility and specificity for CIN2+ in ASCUS postmenopausal women.

P16/Ki-67 dual stain cytology in HPV-positive women performs well for diagnosis of abnormal cervical lesions and should be considered for management of HPV-positive women to avoid unnecessary colposcopy referrals.

P=N/A; N=2426; Completed; Sponsor:AeskuLab Pathology Prague

In OSCC cases, alcohol intake showed statistically significant association with CINtec positivity. P16/Ki67 assessment by dual staining is a promising biomarker for identifying dysplasia in cases with diagnostic dilemmas.

CINtec may support efficient detection of cervical adenocarcinomas.

In conclusion, there is still a need for conventional cytological examination and maybe the addition of immunocytochemistry to confirm the diagnosis and to exclude dysplasia of cervical epithelium. The HPV-HR-Test is not enough as a screening method and may be misleading.

The similar results were observed when identifying CIN2+. Dalton presents the lower false positive rate and better efficacy in identifying high-grade CIN than CINtec PLUS, suggesting that Dalton may be superior to CINtec PLUS and an alternative technique for triaging primary HPV-positive women in cervical cancer screening.

"Roche...announced that results from the IMPACT (IMproving Primary screening And Colposcopy Triage) trial demonstrate clear patient benefit in using Roche’s CINtec PLUS Cytology dual-stain biomarker technology as a triage test for women who test positive for high-risk human papillomavirus (HPV). The data from the trial, established from a study cohort of more than 35,000 women aged 25-65 years, was published recently in the International Journal of Cancer."

After 2 years of follow-up biopsy confirmed 38 HSILs and 2 glandular lesions, all of them were HPV positive. Conclusion* Screening based on HPV testing with selective 16/18 genotyping and p16/Ki-67 triage proved during three years four times more high-grade lesions including glandular lesions than standard screening based on Pap smears.

The odds of HSIL increased almost 21 times in those positive for this biomarker. Our results encourage further investigation on the use of p16/Ki-67 dual staining in anal cancer screening for HIV-uninfected and HIV-infected MSM.

P16/Ki67 expression was observed in the only sample diagnosed as HSIL by biopsy, but only one of the seven samples diagnosed as low grade squamous intraepithelial lesion (LSIL) was p16/Ki67+. Conclusion The results suggest that p16/Ki67 immunostaining is a method that may be useful for improving cytology specificity in detecting high-grade anal squamous intraepithelial lesions.

P16/Ki67 expression was observed in the only sample diagnosed as HSIL by biopsy, but only one of the seven samples diagnosed as low grade squamous intraepithelial lesion (LSIL) was p16/Ki67+. Conclusion The results suggest that p16/Ki67 immunostaining is a method that may be useful for improving cytology specificity in detecting high-grade anal squamous intraepithelial lesions.

P16/Ki67 expression was observed in the only sample diagnosed as HSIL by biopsy, but only one of the seven samples diagnosed as low grade squamous intraepithelial lesion (LSIL) was p16/Ki67+. Conclusion The results suggest that p16/Ki67 immunostaining is a method that may be useful for improving cytology specificity in detecting high-grade anal squamous intraepithelial lesions.

The poor sensitivity of VIA renders it unsuitable as a triage test for HPV positive women. The utility of p16/Ki-67 dual stain cytology as a triage test for HPV positive women in LMICs should be further studied.

HPV positive women exposed to tobacco smoke are at a higher risk of testing positive for p16/Ki-67 co-expression. Risk of high-grade disease is almost doubled in women who are exposed to tobacco smoke.

"Corresponding values considering an LSIL threshold were 42.8% (36.8-49.0) and 35.0% (30.1-40.1). Dual-stained cytology and HPV testing had similar performance, although the former improved the specificity by 7.9% and 9.6% for CIN2+ and CIN3+, respectively."