Diagnostic accuracy of high-risk HPV DNA and cytology in diagnosing precancerous and early malignant cervical lesions: a protocol for a systematic review and meta-analysis

Persistent infection with high-risk hr-HPV is a major cause in the aetiopathogenesis of cervical cancer. Early detection by screening is the best strategy for prevention. Two major screening techniques hr-HPV DNA and Pap smear, target the disease condition at two different timepoints in the natural progression of cervical cancer, one at the initial stage and the other at the level of cytological changes, respectively. Our objectives are to determine the diagnostic accuracy of hr-HPV DNA testing and compare it with that of Pap smear and co-testing in detecting early cancer lesions. We will search electronic databases, including MEDLINE, Embase, Cochrane, and Scopus for studies that reported the diagnostic accuracy of hr-HPV DNA testing alone or in combination with Pap in women of any age undergoing cervical cancer screening. We will include studies that evaluated WHO-prequalified HPV-DNA for the detection of precancerous (CIN1–3) and early malignant cervical lesions (FIGO Stage IA) against histopathological examination. Two reviewers will independently screen the eligible articles, and we will assess methodological quality using QUADAS-2 and QUADAS-C. A bivariate model will be used for meta-analysis to estimate summary sensitivity and specificity wherever possible. Certainty of evidence will be assessed using the GRADE approach for diagnostic test accuracy studies. We anticipate biases, challenges, heterogeneity from data, settings, and methods. However, the work aims to provide more information on the diagnostic accuracy of hr-HPV DNA tests for cervical cancer, supporting evidence-based prevention and early detection strategies. PROSPERO CRD420251251393.