Comparative clinical significance of HPV DNA, HPV E6/E7 mRNA, and p16INK4a in cervical cancer among Indian and USA populations: a meta-analysis and systematic review
摘要
This systematic review and meta-analysis was registered with PROSPERO (Registration No. CRD420251130849) and conducted in accordance with PRISMA 2020 guidelines. A comprehensive literature search of PubMed, Web of Science, and SciencDirect (2000–2025) identified English-language studies reporting the diagnostic performance of HPV DNA, HPV E6/E7 mRNA, and p16INK4a for cervical cancer. Studies providing sufficient data to calculate sensitivity and specificity were included. Pooled estimates were generated using a random-effects model,heterogeneity was assessed using the I2 statistic, and methodological quality was evaluated with the QUADAS-C tool. Overall, 77 studies involving 17,558 women were included. HPV DNA demonstrated a pooled sensitivity of 0.783(95% CI: 0.611–0.956) and specificity of 0.731 (95% CI: 0.584–0.877), with considerable heterogeneity (I2 = 88–96%). HPV E6/E7 mRNA showed the highest diagnostic accuracy, with a pooled sensitivity of 0.950 (95% CI: 0.930–0.970) and specificity of 0.972 (95% CI: 0.959–0.986). Although substantial heterogeneity was observed (I2 = 90%, p < 0.01), the biomarker demonstrated consistently superior diagnostic performance across studies. p16INK4a yielded a pooled sensitivity of 0.874 (95% CI: 0.758–0.989) and a specificity of 0.756 (95% CI: 0.56–0.950), with high heterogeneity (I2 = 92–96%), indicating marked inter-study variability. Among the evaluated biomarkers, HPVE6/E7 mRNA exhibited the highest diagnostic accuracy and sensitivity for cervical cancer detection in both Indian and U.S. populations. Nevertheless, despite its promising performance, larger, well-designed multicenter studies with standardized methodologies and external validation are needed before these biomarkers can be reliably implemented in routine clinical practice.