Performance analysis of Human Papillomavirus E6/E7 mRNA and DNA tests on cervical samples as a tool for cervical cancer screening and colposcopy triaging

Background: Positive human papillomavirus (HPV) E6/E7 mRNA test on cervical samples is said to predict infection with higher chances of conversion to high-grade disease. We conducted a comparative study on the performance of E6/E7 mRNA, HPV DNA, and pap test on cervical smears and evaluated if mRNA can help in the reduction of colposcopy referrals. Methods: A prospective observational study was conducted in Sikkim, where 200 sexually active women, 18-65 years of age, who attended the outpatient clinic of a referral hospital and 3 district hospitals of Sikkim, were enrolled. Physician-collected cervical samples were evaluated for high-risk HPV using E6/E7 mRNA, HPV DNA, and pap tests. Women who were positive were followed up with colposcopy and pap test. Pregnant, hysterectomized, or women with malignancy were excluded. Results: HPV prevalence was 13%, of which HPV DNA test detected the highest (9%). Lost to follow-up for colposcopy was 23%. The HPV DNA had highest sensitivity (76.9%), while specificity was highest for mRNA (85.71%). Logistic regression showed a significant correlation between HPV mRNA and age at first sexual act (coefficient 0.185, OR 0.83, p 0.048). Significant association was seen between HPV mRNA and Cervical intraepithelial Neoplasia 2+ ( p 0.037). Conclusion: HPV DNA test has high sensitivity, making it ideal for screening but mRNA test with higher specificity and significant correlation with CIN2+ is useful in selecting cases for colposcopy. Therefore, using HPV DNA test for screening followed by mRNA test on positive cases would be ideal for colposcopy triaging.