A prospective observational study on the value of HPV E6/E7 oncoprotein immunocytochemistry for triaging HPV-positive...

While human papillomavirus testing has become the primary screening modality for cervical cancer prevention, its implementation necessitates supplementary triage strategies. The viral oncoproteins E6 and E7, serving as primary mediators of high-risk HPV (hrHPV)-induced carcinogenesis, emerge as viable candidates for this risk stratification. We aimed to examine the clinical diagnostic performance of HPV E6/E7 immunocytochemical (ICC) assay in exfoliated cervical cells samples, to investigate the feasibility of using it as a potential biomarker in clinical triage algorithms for hrHPV-positive populations.

We prospectively collected and analyzed 1,005 hrHPV-positive cases from Beijing Obstetrics and Gynecology Hospital, Capital Medical University during September 2023 and March 2025. The diagnostic and triaging performance of HPV E6/E7 ICC assay were evaluated by sensitivity, specificity, positive predictive values, negative predictive values and operating characteristic curve.

When used to detect CIN2+, the sensitivity of HPV E6/E7 ICC detection is (0.88, 95% CI: 0.82-0.92), which is better than that of cytological detection (0.609, 95% CI: 0.53-0.67), χ ² = 26.23, p < 0.05; the NPV of. HPV E6/E7 ICC detection is (0.95, 95% CI: 0.92-0.97), which is better than that of cytological detection (0.85, 95% CI: 0.82-0.88), χ ² = 38.14, p < 0.05. When the HPV typing test result is 16/18+,the sensitivity of HPV E6/E7 ICC detection is (0.93, 95% CI:0.86-0.96), which is better than that of cytological detection (0.61, 95% CI:0.52-0.70), χ ² = 33.47, p < 0.05; the NPV of HPV E6/E7 ICC detection is (0.940, 95% CI:0.89-0.97), which is better than that of cytological detection (0.81, 95% CI:0.75-0.85), χ ² = 13.84, p < 0.05. When the HPV typing test result is other hrHPV type, the sensitivity of HPV E6/E7 ICC detection is (0.81, 95% CI:0.71-0.89), which is better than that of cytological detection (0.75, 95% CI:0.64-0.84), χ ² = 0.914, p = 0.339; the NPV of HPV E6/E7 ICC detection is (0.95, 95% CI:0.92-0.97), which is better than that of cytological detection (0.91, 95% CI:0.86-0.94), χ ² = 4.29, p = 0.038.

HPV E6/E7 ICC assay with high-sensitivity feature may be potential new biomarkers for hrHPV positive women. In addition, its triaging performance is better than that of cytology.