Recent Advances in HPV Detection: From Traditional Methods to Nanotechnology and the Application of Quantum Dots

Abstract

Cervical cancer, a significant public health concern, demands precise and expeditious detection methods to curb the spread of human papillomavirus (HPV). The early detection of cervical cancer remains a critical challenge in developing reliable and efficient screening tools to meet the demand for controlling cervical cancer. Traditional detection techniques are often cumbersome, costly, and inadequate for on-site HPV testing. Nanotechnology, with its unique electrical, chemical, and optical properties, has emerged as a pivotal component in the development of biosensors for rapid and reliable HPV detection. This article provides a comprehensive review of the advancements in cervical cancer detection, encompassing traditional methods, emerging protocols, and novel quantum dots (QDs)-based approaches for detection. The review examines the application of various nanomaterials in electrochemical and photoelectrochemical biosensors for the diagnosis of cervical cancer, with these innovations offering a significant improvement over conventional approach. Furthermore, we detail the synthesis methods of QDs and their properties, illustrate the substantial enhancement in sensor performance achieved through their applications, and elucidate the improvements and challenges associated with these new protocols while highlighting the potential application prospects of novel QDs technology in HPV detection.

Keywords: biosensors; cervical cancer; early diagnosis; human papillomavirus detection; nanotechnology; quantum dots.

Graphical abstract

Figure 1

(A) Schematic diagram for the ECL biosensing platform based on PCN-224/ZnO nanocomposites coupled with cyclic amplification and chain reaction for HPV-16 assay. Reproduced from Wu D, Dong W, Yin T, et al. PCN-224/Nano-Zinc oxide nanocomposite-based electrochemiluminescence biosensor for Hpv-16 detection by multiple cycling amplification and hybridization chain reaction. Sensors and Actuat B Chem. 2022;372:132659. © 2022 Elsevier B.V. All rights reserved. (B) Illustration of the modularized electrochemical sensing strategy based on CRISPR/Cas-mediated controllable MB release/enrichment system for ultrasensitive determination of HPV-16, including target recognition module (a), signal amplification module (b), and signal transduction module (c).Reproduced from Wang H, Niu Y, Liu H, et al. A modularized universal strategy by integrating CRISPR/Cas with nanoporous materials for ultrasensitive determination of nucleic acids. Chem Eng J. 2025;506:160065. © 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies. (C) Schematic diagram of an electrochemical nanobiosensor with CRISPR/Cas14a system integrated with bipedal DD walker to detect HPV16 E7 serum samples. Reproduced from Yue Y, Liu M, Ma M, et al. CRISPR/Cas14a integrated with DNA walker based on magnetic self-assembly for human papillomavirus type 16 oncoprotein E7 ultrasensitive detection. Biosens Bioelectron. 2025;272:117135. © 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies. (D) Schematic illustration of the fabrication procedures of Fe₃O₄@Au@PEI@HPP NPs and the strategy of HPV genotype detection in buffer or in 100% serum based on Fe₃O₄@Au@PEI@HPP NPs. Reproduced from Chen L, Liu M, Tang Y, et al. Preparation and Properties of a Low Fouling Magnetic Nanoparticle and Its Application to the HPV Genotypes Assay in Whole Serum. ACS Appl Mater Interfaces. 2019;11(20):18637–18644. Copyright © 2019 American Chemical Society.⁹¹

Figure 2

(A) Schematic drawing for our comprehension on the use of TOPO to fragmentize the PC that has formed in a prenuclation stage sample to facilitate the nucleation and growth of colloidal small-size CdS QDs with enhanced particle yield and without the coexistence of the PC and/or MSCs. Reproduced from Li L, Zhang J, Zhang M, et al. Fragmentation of Magic-Size Cluster Precursor Compounds into Ultrasmall CdS Quantum Dots with Enhanced Particle Yield at Low Temperatures. Angew Chem Int Ed Engl. 2020;59(29):12013–12021. © 2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. (B) Schematic diagram of the synthesis and multifunctional applications of N-SiQDs. Reproduced from Wang YF, Pan MM, Song YL, et al. Beyond the fluorescence labelling of novel nitrogen-doped silicon quantum dots: the reducing agent and stabilizer for preparing hybrid nanoparticles and antibacterial applications. J Mater Chem B. 2022;10(36):7003–7013. © 2022 Royal Society of Chemistry. (C) This schematic represents the key features of QDs that are critical for HPV detection, emphasizing their size-adjustable luminescence, tunable emission for wavelength specificity, and robust photostability. It also illustrates the integration of QDs with various materials to form composite structures, enhancing their application in biosensing through magnetic separation, carbon and graphene interfaces, and metal-organic frameworks.

Figure 3

(A) Schematic illustration of the synthesis of POM@CdS QD composites. (B) Schematic illustration of the PEC sensor for detecting HPV 16 DNA. Reproduced from Cheng Y, Sun C, Chang Y, et al. Photoelectrochemical biosensor based on SiW12@CdS quantum dots for the highly sensitive detection of HPV 16 DNA. Front Bioeng Biotechnol. 2023;11:1193052. Copyright © 2023 Cheng, Sun, Chang, Wu, Zhang, Liu, Ge, Li, Li, Sun and Zang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). (C) Schematic illustration of CRISPR-Cas12a-based PEC biodetection toward HPV-16 by disassembly of Z-Scheme heterojunction among TiO₂, Au NPs, and CdS QDs. Reproduced from Li Y, Zeng R, Wang W, et al. Size-Controlled Engineering Photoelectrochemical Biosensor for Human Papillomavirus-16 Based on CRISPR-Cas12a-Induced Disassembly of Z-Scheme Heterojunctions. ACS Sens. 2022;7(5):1593–1601. Copyright © 2022 American Chemical Society.

Figure 4

(A) Schematic illustration of the PEBA setup for HPV genotyping and a comparison between the proposed PEBA and conventional photoelectrochemical testing system. (B) Schematic depiction of the fabricated PEBA for detecting HPV-related genes. (C) Schematics of the PEBA assembly process. (D) Photocurrent responses of the PEBA toward different concentrations of synthetic HPV16 oligonucleotide standard with from 0 fM to 1 nM. Insert: the calibration curve of ΔI/I0 versus HPV16 target concentration. (E) Photocurrent responses of the PEBA to different concentrations of HPV DNA subtype plasmids (0, 0.6, 3, 6, 60, 300, 600 copies/μL). (F) The calibration curves of photocurrent responses versus the HPV DNA concentrations from 0.6 to 600 copies/μL. Error bars represented the standard deviations of three independent experiments. Reproduced from Sun Y, Liu J, Peng X, et al. A novel photoelectrochemical array platform for ultrasensitive multiplex detection and subtype identification of HPV genes. Biosens Bioelectron. 2023;224:115059. © 2023 Published by Elsevier B.V.

Figure 5

(A) The ECL performance. (B) ECL response of the biosensor with (a) 0.1 nM, (b) 1 nM, (c) 10 nM, (d) 20 nM, (e) 50 nM, (f) 100 nM and (g) 200 nM HPV 16 DNA. (C) Schematic illustration of reductive Cu(I) particles catalyzed Zn-doped MoS₂ QD-based ECL biosensor. (D) Visualized ECL images processed by the self-developed software with (a) 0.1 nM, (b) 10 nM, (c) 50 nM, (d) 100 nM and (e) 200 nM HPV 16 DNA. Reproduced from Nie Y, Zhang X, Zhang Q, et al. A novel high efficient electrochemiluminescence sensor based on reductive Cu(I) particles catalyzed Zn-doped MoS2 QDs for HPV 16 DNA determination. Biosens Bioelectron. 2020;160:112217. © 2020 Elsevier B.V. All rights reserved.

Figure 6

(A) Schematic representation of the proposed electrochemical DNA biosensor. (B) DPV responses of the proposed biosensor with various TD concentrations for HPV-16 detection. (C) the correlation between DPV peak current ΔI and TD concentrations, obtained by an inserted calibration with the logarithm of the TD concentrations, error bars = SD (n = 3). Reproduced from Yu J, Dong C, Yang Y, et al. Electrochemical DNA biosensor for HPV-16 detection based on novel carbon quantum dots/APTES composite nanofilm. Microchem J. 2024;204:110949. © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies. (D) Optical biosensing system utilizing MGPs and CdTe/ZnSe QDs coupled with nucleic acid probes. Reproduced from Jimenez Jimenez AM, Moulick A, Bhowmick S, et al. One-step detection of human papilloma viral infection using quantum dot-nucleotide interaction specificity. Talanta. 2019;205:120111. © 2019 Elsevier B.V. All rights reserved. (E) Schematic representation for principle of sensitive DNA detection based on GQDs ECL coupled with cycling amplification technique. Reproduced from Jie G, Zhou Q, Jie G. Graphene quantum dots-based electrochemiluminescence detection of DNA using multiple cycling amplification strategy. Talanta. 2019;194:658–663. © 2018 Elsevier B.V. All rights reserved.

Figure 7

(A) Schematic outlining the method for analyzing HPV16 and HPV18. (B) Fluorescence spectra of QDs-ssDNA reacting with NiTPP solutions of different concentrations (Ex=300 nm, Em_gQDs=567 nm, Em_rQDs=678 nm). (C) Fluorescence spectra of QDs-ssDNA reacting with different concentrations of HPV16 and HPV18 (Inset: fluorescence changes under ultraviolet lamp). (D) Linear relationship between gQDs-gDNA and HPV16. (E) Linear relationship between rQDs-rDNA and HPV18. reproduced from Jiang X, Yin C, Wu M, et al. Fluorescent switch based on QDs modified DNA probe and NiTPP for simultaneous dual color sensitive sensing of HPV16 and HPV18. Sensors and Actuat B Chem. 2024;403:135128. © 2023 Elsevier B.V. All rights reserved.