Farzaneh Bilan, Behboud Jafari, Jalal Gharesouran, Amir Hossein Kiani Darabi, Sahar Tajeddini, Maryam Rezazadeh, Soudeh Ghafouri-Fard
The compiled evidence indicates that HPV-responsive lncRNAs represent promising candidate biomarkers for diagnosis and prognosis, and may warrant further investigation as therapeutic targets; however, prospective validation in independent cohorts is required before clinical translation.
BACKGROUND: Long non-coding RNAs (lncRNAs) are emerging regulators of HPV-driven carcinogenesis with potential diagnostic and prognostic value in cervical cancer (CC). A contemporary synthesis of clinical and mechanistic evidence is necessary to prioritize candidates for translational development.
METHODS: We conducted a systematic scoping review of studies assessing lncRNAs in HPV-associated CC. Searches across major databases yielded 556 records; after de-duplication (n = 220) and screening, 154 full texts were assessed, and 27 studies met the inclusion criteria. No formal quality or risk-of-bias assessment was performed, consistent with the scoping review framework. The extracted data included study identifiers, lncRNA identity, HPV association, sample type/size, expression in HPV-positive disease, diagnostic metrics (AUC/sensitivity/specificity), prognostic measures (survival statistics), and mechanistic findings.
RESULTS: The 27 studies described 29 unique lncRNAs, which were upregulated in 75% and downregulated in 25% of the studies. Tissue-derived analyses predominated (21 studies), with cell line experiments in 13 studies and circulating assays in a minority (serum 3; plasma 2). Diagnostic performance was reported in 13/27 studies (∼48%), and prognostic associations were reported in 22/27 (∼81.5%). MALAT1 and GATA6-AS1 were each evaluated in two independent studies, whereas HOTAIR was investigated in two studies with different types of evidence. Mechanistic data consistently implicated HPV E6/E7-dependent regulation, ceRNA/miRNA sponging, cell cycle control, and epithelial-mesenchymal transition.
CONCLUSION: The compiled evidence indicates that HPV-responsive lncRNAs represent promising candidate biomarkers for diagnosis and prognosis, and may warrant further investigation as therapeutic targets; however, prospective validation in independent cohorts is required before clinical translation.