Cervical cancer on-site mass-screening device utilizing multiple biomarkers in Swab samples for surveillance in the resource limited areas of India

At the World Health Assembly in August 2020, a target was set to eradicate cervical cancer globally by 2030 (incidence < 4/100,000) with 90% vaccination coverage, 70% screening coverage, and 90% treatment coverage. India has a worrying prevalence of between 6 and 30 percent, due to HPV infections and low awareness in rural areas. HPV infections and cervical cancer disease development window period is anytime between 6 and 20 years. Thus mass screening of the population will play a very crucial role. KayaCervi, a lab-free, point-of-care mass screening device based on fluorescence EEM technology, consisting of a cartridge, a reader and a microchip was clinically validated in the study. Initially, ten biomarkers were compared using ELISA and Pap smear. Four (p16INK4a, Ki 67, HPV16, HPV18) were selected. Swab validation was performed with cohorts’ of 200 hospital patients and 800 healthy community females, benchmarked against LBC to optimize sensitivity and ensure high specificity. The community-based validation study was to evaluate the performance of the device as a mass-screening tool among apparently healthy women. In such settings, the majority of participants are disease-negative, and high specificity is essential to minimize false-positive results, unnecessary referrals, psychological distress, and healthcare costs. Sensitivity was measured during the standardization phase by screening participants and confirmed positive cases. Initial findings used biomarkers p16NK4A, Ki67, HPV16, and HPV18 to categorize women into high, moderate, and low risk. The design of the cartridge ensured efficient sample capture and quantification, integrating mechanisms to correct for various light wavelengths during analysis. In community-based evaluation (N = 801), the device demonstrated an overall agreement of 98.0% with the reference standard. Cohen's kappa coefficient was 0.545, indicating moderate agreement beyond chance. The device achieved 100% sensitivity, 98.0% specificity, 38.5% positive predictive value, 100% negative predictive value, and 98.0% overall accuracy and identified high percentage of infections in the apparently healthy women comparable to the liquid based cytology reading done for the relative cellular changes. This study validated KayaCervi, a portable, laboratory-independent point-of-care diagnostic device developed to address India's high burden of cervical cancer. The device integrates a fluorescence-based detection platform with a four-target biomarker panel comprising p16INK4a, Ki-67, HPV16, and HPV18, achieving a specificity of 86–90% in community-based rural screening. As a rapid, low-cost, and user-friendly screening tool, KayaCervi has the potential to democratize access to cervical cancer screening by overcoming barriers related to laboratory infrastructure, trained personnel, and patient follow-up. Further, it include the need for larger, prospective, multicenter studies involving geographically diverse populations, with the biomarker panel and diagnostic thresholds predefined before evaluation and with an appropriate independently established reference standard. Such studies will be essential to confirm the reproducibility, generalizability, diagnostic performance, clinical utility and implementation feasibility of KayaCervi before large-scale deployment. Its suitability for decentralized, large-scale population screening is particularly important given the prolonged natural history of cervical carcinogenesis, where persistent HPV infection may take 15–20 years to progress to invasive cancer, providing a critical window for early detection and timely intervention. This highlights the public health significance by emphasizing the long preclinical phase and the opportunity for early intervention.