Comparison of the sensitivity and specificity of p16/Ki-67 dual staining and HPV DNA testing of abnormal cervical cytology in the detection of histology proven cervical intraepithelial neoplasia grade 2 and above (CIN 2+)

Introduction: Human papillomavirus (HPV) testing is used as a means of triaging cervico-vaginal smears with low grade squamous abnormalities or as part of co-testing with cytology. While HPV testing has a high sensitivity, it has a low specificity in detecting cervical intraepithelial neoplasia grade 2 and above (CIN 2+) leading to unnecessary colposcopy referrals. We investigate the accuracy of the p16/Ki-67 dual immunocytochemical stain in determining the presence of CIN 2+ lesions on histology and its potential as a superior biomarker for triage. Methods: Liquid based cervico-vaginal cytology specimens with squamous abnormalities and corresponding histology from 97 women with subsequent colposcopy and biopsy were included. The specimens were then subjected to the dual stain and Roche Cobas 4800 multiplex real time PCR HPV DNA testing. The sensitivity and specificity of the dual stain and HPV testing were calculated using CIN 2+ on histology as a reference standard. Results: The sensitivity and specificity of the dual stain in detecting histology proven CIN 2+ was 93.7% and 76.5% while HPV testing was 85.7% and 14.7% respectively. Of the 44 women with ASCUS or LSIL on cytology, the dual stain also reduced the number of unnecessary colposcopy referrals from 27 to 7 when used as a triage marker compared to HPV testing. Conclusion: p16/Ki-67 dual stain was more sensitive and specific than HPV testing in determining the presence of CIN 2+ on histology. It could triage low grade cervico-vaginal specimens more effectively and potentially help women avoid unnecessary colposcopies. Future studies are needed to further evaluate its role in cervical cancer screening programmes.