How Liquid Biopsies are Transforming Cancer Detection in India

WORLD CANCER DAY / FEBRUARY 4

Cancer is a dreaded disease, mostly detected at late stages but it can be prevented or cured, if detected early. Cancer detection has long been dependent on tumour tissue biopsies which can be obtained by surgi­cal procedures which are both resource- and labour-intensive and are usually performed only after symptoms become clinically evident. While histopathology (microscopic study of diseased tissues and cells) remains the diagnostic gold standard, its reliance on surgical or needle-based sampling creates inherent bottlenecks for population screening, early diagnosis, and easy monitoring.

In India, a substantial proportion of cancers (~70%) are still diagnosed at advanced stages, and these limitations translate directly into delayed interven­tion, higher treatment costs, and poor survival outcomes. The need of the hour is to have a patient-friendly, simple di­agnostic tests on easily available body fluids such as saliva, blood, and urine that enable early detection and real-time disease tracking.

NON-INVASIVE OR LIQUID BIOPSIES

Advances in molecular biomarkers-based diagnostics have moved cancer diagnosis beyond tissue-centric models towards non-invasive diagnosis using liq­uid biopsies. By analysing biofluids such as blood, saliva, and urine as liquid biop­sies including circulating tumour DNA (ctDNA), cell-free RNA, extracellular vesicles, circulating tumour cells, mi­crobial signatures (in virus/bacteria- in­duced cancers) and metabolites provide an easy and early diagnosis approach without resorting to invasive/compres­sive surgical procedures. These tests can be repeated over time, enabling dynamic assessment of disease evolution, therapy response, and minimal residual disease. What was once confined to only research laboratories is rapidly having wider clini­cal applications, driven by improvements in DNA/RNA sequencing technologies, digital PCR, bioinformatics pipelines, and now by application of artificial in­telligence.

For India, the promise of liquid bi­opsy-based detection extends far beyond technological novelty. Non-invasive diagnostics align strongly with public health priorities by offering accessible, scalable, and potentially cost-effective tools suitable for diverse healthcare settings from tertiary cancer centres to community-based screening pro­grammes. Their relevance is particularly very high in India as the burden of cancer is increasing, particularly for breast, cer­vical, oral, ovarian, colorectal, lung and pancreatic cancers, where screening cov­erage remains uneven and social barriers frequently delay clinical presentation. By enabling early detection and treat­ment, risk stratification, and monitoring through simple biofluid sampling, liquid biopsies can help shift cancer care from a reactive, late-stage model to a proactive, precision-driven early detection and ef­fective management of cancer.

LIQUID BIOPSIES AT THE MOLECULAR CORE: DECODING TUMOURS WITHOUT TOUCHING THEM

Liquid biopsies are grounded in a funda­mental biological reality: tumours con­tinuously shed molecular materials into circulation. As cancer cells grow, die, and interact with their microenviron­ment, they release a spectrum of genetic, epigenetic, and metabolic signals that re­flect the underlying biology and natural history of the disease. Capturing these signals allows clinicians to ‘read’ the tumour without physically accessing it.

Among the most widely studied analytes is circulating tumour DNA (ctDNA), a small fraction of cell-free DNA that carries tumour-specific mu­tations, copy-number changes in driver genes, and methylation patterns. With highly sensitive platforms such as digital PCR and next-generation DNA/RNA sequencing and, ctDNA can be used to detect cancer-associated alterations, estimate tumour burden, and identify emerging resistance well before clini­cal or radiological progression becomes apparent.

Liquid biopsies also include cell-free RNA molecules, such as microRNAs and long non-coding RNAs, which re­flect dysregulated gene expression in pa­tients. Many of these RNA species are packaged within exosomes, nanoscale vesicles actively secreted by cancer cells. Exosomes carry DNA, RNA, proteins, and lipids, and play an important role in shaping immunity and the tumour microenvironment. From a diagnostic perspective, they offer a stable and in­formation-rich source of biomarkers, particularly valuable when ctDNA levels are very low in early-stage disease.

Another component is circulating tumour cells, rare intact cancer cells that detach from primary tumours and enter the bloodstream. Although techni­cally challenging to isolate, they provide unique insights into metastatic potential, how stationary epithelial cells become migratory metastatic cancer cells, and therapy resistance.

An emerging frontier biomarkers analysis uses metabolites and cancer-associated microbiomes. Tumours pro­foundly reprogramme cellular metabo­lism and interact with local microbial ecosystems. Metabolomic profiles and microbial DNA signatures are increas­ingly linked to inflammation-driven car­cinogenesis, especially in mucosal can­cers such as oral, stomach, melanoma, lymphoma, etc., an area of particular relevance for India.

CHOOSING THE RIGHT BIOFLUID

The choice of biofluids requires feasibil­ity, patient acceptability, and biological relevance. While blood remains the most widely used body fluid, saliva and urine or sputum and stool are gaining promi­nence due to their non-invasive nature of collection, ease of repeat sampling, and suitability for large-scale screening.

For oral and cervical cancers, these biofluids are not merely convenient but biologically meaningful and show al­most 100% correlation with tissue bi­opsy. Saliva, in direct contact with the mouth cavity, is enriched with tumour-proximal signals. Urine offers a privacy-preserving alternative for cervical cancer screening, potentially improving par­ticipation where pelvic examinations or colposcopy-driven biopsy or smear col­lection pose barriers.

LIQUID BIOPSIES IN ORAL AND CERVICAL CANCERS: HIGH-IMPACT USE IN INDIA

Oral and cervical cancers together ac­count for a substantial fraction of India’s most common cancer burden, and late-stage diagnosis remains a major chal­lenge. Oral cancer with poor survival largely driven by delayed presentation and lacks reliable non-invasive screen­ing tools. Current diagnostic pathways depend on visual inspection followed by tissue biopsy approaches that are impractical for early detection or com­munity-level screening. Saliva-based liq­uid biopsies offer a promising solution. Tumour-derived DNA/RNA, inflam­matory mediators, microbial signatures, and metabolites can all be detected in saliva, providing early molecular clues of malignant transformation. Such ap­proaches could enable risk-stratification of oral potentially malignant disorders, helping identify individuals who need urgent biopsy versus those who can be safely monitored. Cervical cancer, despite being one of the most preventable malignancies, remains a leading cause of cancer-related deaths among Indian women. Persistent infection with high-risk human papillo­maviruses (HR-HPVs) precedes invasive cancer by years, creating a window for early intervention. Yet, occurrence of more than a decade long cervical precan­cerous lesions also allow early detection and cancer prevention. Liquid biopsy-based detection of viral DNA, integra­tion patterns, host methylation changes, and dysregulated microRNAs can en­hance existing screening programmes. Sampling options that include urine and blood can improve compliance and allow longitudinal monitoring of disease risk.

WHY LIQUID BIOPSIES MATTER FOR CANCER DETECTION IN INDIA

BEYOND DETECTION: MONITORING AND PRECISION CARE

Perhaps the strongest clinical advantage of liquid biopsies lies in serial disease monitoring. Because biofluids can be sampled repeatedly, clinicians can track treatment response, detect minimal re­sidual disease, and identify molecular relapse months before conventional im­aging. For cancers prone to recurrence or therapy resistance, such real-time mo­lecular surveillance can support timely, personalised clinical decisions. Impor­tantly, liquid biopsies are best viewed not as replacements for histopathology, but as complementary tools. If used strategi­cally, they can function as triage tests helping determine who requires imme­diate invasive diagnostics, who can be monitored, and who needs intensified follow-up.

SCREENING INNOVATIONS AND CLINICAL TRANSLATION: TAKING LIQUID BIOPSY FROM LAB TO LAND

The science of liquid biopsies is advanc­ing rapidly, but their true value lies in translation turning molecular signals into actionable, scalable and affordable tools. In India, translation is shaped by three priorities: non-invasive sampling, high analytical sensitivity in early dis­ease, and deployability across healthcare settings.

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Non-invasive sampling models built for scale support repeat testing and com­munity outreach. Saliva is particularly suited to oral cancer detection, while urine-based approaches can enhance cervical cancer screening by improv­ing privacy and participation. Because early-stage cancers shed very low levels of tumour material, modern strategies increasingly rely on multi-marker panels that integrate complementary signals ctDNA alterations, RNA signatures, exosomal cargo, metabolomic patterns, and microbial profiles to improve sen­sitivity while maintaining specificity. A realistic and impactful goal is to use liquid biopsies as triage tools rather than replacements for histopathology. Risk stratification can help determine who needs immediate biopsy, who can be monitored, and who requires inten­sified follow-up. In post-treatment set­tings, serial testing can track response, detect resistant clones, identify minimal residual disease, and flag early relapse. For population-level impact, platforms must match operational realities. Trans­lation depends on affordable assay for­mats, standardised pre-analytical work­flows (sample collection, stabilisation, transport and storage), quality control, harmonised reporting, and robust data analytics, including artificial-intelli­gence-assisted risk models for multi-omic signals. Without standardisation, even promising biomarkers fail to trans­late. With this, multi-centre adoption becomes feasible.

POLICY OUTLOOK: A NATIONAL

OPPORTUNITY TO DEMOCRATISE EARLY CANCER DETECTION

Liquid biopsies represent more than a diagnostic upgrade; they offer a strate­gic opportunity to reshape cancer detec­tion in India around early diagnosis, risk stratification, and equitable access. By harnessing tumour-derived signalling molecules in blood, saliva, and urine, these platforms can shift cancer care from late-stage intervention to proactive, precision-informed early screening, early treatment and monitoring. This shift is particularly urgent for high-burden can­cers such as oral, cervical, breast and lung cancers, where screening gaps and delayed presentation continue to under­mine outcomes.

To convert promise into population impact, India needs a coordinated efforts and roadmap that strengthen the entire translation pipeline:

Priority must be given to large pro­spective cohorts, standardised sample workflows, and clinically meaningful endpoints such as early detection, pro­gression prediction, treatment response, minimal residual disease, and recurrence risk. Equally important is implementa­tion design: embedding liquid biopsies into well-defined clinical pathways that guide triage, referral, and follow-up, while ensuring that confirmatory diag­nostics remain robust, accessible and affordable.

India is well-positioned to lead in this space because the need is urgent, the in­novation ecosystem is expanding, and the benefits are clear—simpler sampling, smarter triage, earlier detection, and bet­ter follow-up. With rigorous validation, quality standards, and thoughtful imple­mentation, the transition from invasive to non-invasive diagnostics can deliver what matters most, early diagnosis, im­proved survival, reduced barrier, proce­dural burden, and more equitable cancer care across diverse populations.

*Dr Shilpi Gupta is Assistant Pro­fessor at the Amity Institute of Molecu­lar Medicine and Stem Cell Research (AIMMSCR), Amity University, Noida; Dr Prabhat Kumar, is ICMR-DHR-Young Scientist, AIMMSCR, Amity University, Noida; and Prof (Dr) Bhudev C Das is the Chairman, AIMMSCR, and Dean, Health Sci­ences, Amity University, Noida.