Novel concepts in cervical cancer screening: a comparison of VIA, HPV DNA test and p16INK4a/Ki-67 dual stain cytology in Western Kenya

Abstract

Background Screening of unvaccinated women remains essential to mitigate the high morbidity/mortality of cervical cancer. Here, we compared visual inspection with acetic acid (VIA), recommended by WHO as the most cost-effective screening approach in LMICs, with HPV-based screening, and usage of p16INK4a/Ki-67 dual stain cytology. Methods We prospectively enrolled women participating in a VIA-based cervical cancer screening program in two peri-urban health centers of Kenya. Consenting women had a VIA examination preceded by collection of a liquid-based cytology sample from the cervix stored in PreservCyt medium (Hologic®). Analysis of all samples included a hrHPV DNA test and evaluation of a p16INK4a /Ki-67 (CINtecPLUS®) dual stained slide that was prepared using the ThinPrep® 2000 Processor and evaluated by a pathologist trained in the methodology. Results In 701 of a total of 800 women aged 18–64 years, all three investigations were performed and data could be analyzed. The HPV, VIA and dual stain cytology positivity were 33%, 7%, and 2% respectively. The HPV positivity rate of VIA positive cases was 32%. The five most common HPV types were HPV16, 52, 68, 58 and 35. The OR among HIV infected women of an HPV infection, VIA positivity and positive dual stain cytology were 2.6 (95%CI 1.5–4.3), 1.9 (95%CI 0.89–4.4) and 3.4 (95%CI 1.07–10.9) respectively. The sensitivity of VIA to detect a p16INK4a/Ki-67 positive transforming infection was 13% (95%CI 2–38). Conclusions Primary HPV testing appears feasible and should be considered as a primary screening test also in LMICs. The poor sensitivity of VIA renders it unsuitable as a triage test for HPV positive women. The utility of p16INK4a/Ki-67 dual stain cytology as a triage test for HPV positive women in LMICs should be further studied.

TOP2A/MCM2, p16INK4a, and cyclin E1 expression in liquid-based cytology: a biomarkers panel for progression risk of cervical premalignant lesions

“…For the above, we proposed a panel of three cellular biomarkers (TOP2A/MCM2, p16 INK4a , and cyclin-E), which, according to the statistical analysis and their function, are the most useful for evaluating the exacerbated proliferative activity of cervical cells, which is one of the earliest hallmarks of carcinogenesis. Other studies also indicated the usefulness of a biomarkers panel, based on the dual detection of p16 INK4a /Ki-67 for the screening of cervical lesions induced by HPV [ 13 , 39 , 40 ].…”

Novel biomarkers with promising benefits for diagnosis of cervical neoplasia: a systematic review

“…Recent studies have recommended the implementation of p16/Ki-67 and HPV-DNA tests combination for safe monitoring the recurrence of CIN2+ given that some patients treated for CIN2 and CIN3 tend to relapse overtime [28]. However, there is a serious doubt as to whether a combination p16/Ki-67 assay and VIA may serve as alternative in facilities with resource limitations considering low sensitivity associated with VIA [63,64].…”

Performance of visual Inspection With Acetic Acid for Cervical Cancer Screening as Compared to Human papillomavirus Deoxyribonucleic acid Testing Among Women With HIV in Ethiopia: A Comparative Cross-sectional Study

“…Other studies conducted in Latin America, Asian and African countries, among the general female population reported that the VIA test positivity was 7.1%, 6 9.7%, 8 7.6%, 16 6.6%-16.1%, 26 5.5%-34.4%, 27 6.0%, 28 and 7.0%. 7 Similar studies conducted in Ethiopia among eligible women in the general population also showed varied results. For instance, in Butajira, test positivity of VIA was low (4.7%), 10 and in Jimma, VIA positive result was 12.9%.…”