Extracellular RNAs (exRNAs) packaged within tumor-derived exosomes have emerged as compelling candidates for non-invasive cancer biomarkers and active mediators of oncogenic intercellular communication. Human papillomavirus (HPV)-associated malignancies, principally cervical carcinoma and oropharyngeal squamous cell carcinoma, impose a significant global burden for which early molecular detection remains an unmet clinical need. Exosomes released by HPV-positive tumor cells carry diverse RNA species, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and PIWI-interacting RNAs (piRNAs), whose composition faithfully mirrors the molecular landscape of the originating malignant cell. Protected from extracellular nuclease degradation by their lipid bilayer membrane, these RNA species are detectable in peripheral blood, saliva, and urine, conferring amenability to liquid biopsy strategies. This review provides a comprehensive synthesis of the biogenesis and cargo composition of exosomal extracellular RNAs, their diagnostic and prognostic utility in HPV-associated cancers, their mechanistic contributions to tumor progression and immune evasion, and their emerging potential as therapeutic targets and drug delivery vehicles. Integration of exosomal RNA profiling into clinical oncology holds significant potential; however, rigorous prospective validation and methodological standardization are required before clinical translation can be realized.

Cell-free nucleic acids, particularly microRNAs (miRNAs), have emerged as promising diagnostic biomarkers for disease detection, including cancer, owing to their relative stability, disease-specific expression patterns, and functional involvement in disease pathogenesis. Exhaled breath condensate (EBC) is a non-invasively collected biofluid obtained through tidal breathing and has been shown to contain extracellular nucleic acids derived from the respiratory tract, present in both extracellular vesicle (EV)-associated and EV-free forms, and presents distinctive features that, in some contexts, offer practical advantages over other emerging breath-based diagnostic approaches. This narrative review synthesises previous advances in the characterisation and applications of cell free nucleic acids in EBC as potential diagnostic, prognostic, and monitoring biomarkers, with existing studies largely focused on lung cancers and other non-malignant respiratory pathologies, whilst addressing key methodological challenges and suggesting strategies for standardisation and improved translational utility. Importantly, it also examines the possibility of using EBC-derived nucleic acids to identify conditions in extra-pulmonary organs and broader systemic diseases, considering recent studies, whilst highlighting new research directions to be explored.