AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025380407
Submit to EJMO
Cite this article
5
Download
66
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
ORIGINAL RESEARCH ARTICLE

Comparative analysis of diagnostic methods for high-risk HPV detection: A scoping review and meta-analysis

Rahmi Amtha1* ,  Monica Dwi Hartanti2,3† ,  Nadira Putri Fedin1 ,  Indrayadi Gunardi1† ,  Christopher Andrew Teguh2 ,  Ilham Hizbulloh2 ,  Muhammad Ihsan Rizal4 ,  Yani Kurniawan2 ,  Didik Tulus Subekti3 ,  Christina Safira Whinie Lestari3
Show Less
1 Oral Medicine Department, Faculty of Dentistry, Universitas Trisakti, West Jakarta, Jakarta, Indonesia
2 Biology Molecular Department, Faculty of Medicine, Universitas Trisakti, West Jakarta, Jakarta, Indonesia
3 Center for Biomedical Research, Organization for Health National Innovation and Research Agency, West Java, Indonesia
4 Oral Biology Department, Faculty of Dentistry, Universitas Trisakti, West Jakarta, Jakarta, Indonesia
†These authors contributed equally to this work.
EJMO, 025380407 https://doi.org/10.36922/EJMO025380407
Received: 21 September 2025 | Revised: 24 November 2025 | Accepted: 3 December 2025 | Published online: 27 April 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Download PDF
XML
Cite
Abstract

Introduction: High-risk (HR) human papillomavirus (HPV) is the main cause of cervical cancer and a substantial proportion of oropharyngeal cancers, making early and accurate detection critical for effective screening and prevention, particularly in low-resource settings.

Objective: This study aims to compare the diagnostic accuracy of point-of-care and rapid testing methods for HR-HPV detection.

Methods: We conducted a scoping review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews framework. PubMed/MEDLINE, ScienceDirect, and Scopus were searched for English-language studies published from 2010 through July 2025. Fifteen studies met the inclusion criteria, with eight included in the meta-analysis.

Results: Recombinase polymerase amplification combined with clustered regularly interspaced short palindromic repeats/Cas12a achieved the highest pooled diagnostic performance, with a sensitivity of 0.94 and specificity of 0.97. Polymerase chain reaction-based analyses also showed high accuracy (sensitivity = 0.85; specificity = 0.97) but exhibited considerable heterogeneity across platforms and sample types. Loop-mediated isothermal amplification demonstrated moderate performance (sensitivity = 0.60; specificity = 0.91), while p16 immunohistochemistry offered good sensitivity (0.91) but lower specificity (0.73), supporting its use as a confirmatory rather than primary screening tool. In situ hybridization and next-generation sequencing provided broader genotyping capability but were limited by higher cost and technical complexity.

Conclusion: Polymerase chain reaction remains the clinical gold standard for HR-HPV detection, whereas recombinase polymerase amplification/clustered regularly interspaced short palindromic repeats–Cas12a emerges as a promising alternative for decentralized, low-resource screening. Future multi-center studies should standardize reporting, expand genotype coverage beyond HPV-16 and HPV-18, and assess cost, turnaround time, and operational feasibility to ensure that advances in HR-HPV diagnostics translate effectively into public health benefit.

Keywords
Diagnostic
Human papillomavirus
Point of care
Rapid diagnostic
Funding
This study was funded by the Research Grant “Program Hibah Penelitian Fundamental” (0070/C3/AL.04/2025 23, 1014/LL3/ AL.04/2025, and 479/A/LPPM/USAKTI/ VI/2025) from the Directorate General of Higher Education, Research, and Technology, under the Ministry of Education, Culture, Research, and Technology of Indonesia.
Conflict of interest
The authors have no conflicts of interest associated with the material presented in this paper.
References
  1. Bosch FX, Lorincz A, Munoz N, Meijer CJLM, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002;55(4):244-265. doi: 10.1136/jcp.55.4.244

 

  1. Wang X, Huang X, Zhang Y. Involvement of Human Papillomaviruses in Cervical Cancer. Front Microbiol. 2018;9:2896. doi: 10.3389/fmicb.2018.02896

 

  1. Wongsamart R, Bhattarakasol P, Chaiwongkot A, et al. Multiplex recombinase polymerase amplification for high- risk and low-risk type HPV detection, as potential local use in single tube. Sci Rep. 2023;13(1):4911. doi: 10.1038/s41598-023-28038-9

 

  1. Owosho AA, Wiley R, Stansbury T, Gbadamosi SO, Ryder JS. Trends in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma Incidence, Vermont 1999-2013. J Community Health. 2018;43(4):731-737. doi: 10.1007/s10900-018-0477-1

 

  1. Whitton AF, Knight GL, Marsh EK. Risk factors associated with oral Human Papillomavirus (HPV) prevalence within a young adult population. BMC Public Health. 2024;24(1):1798. doi: 10.1186/s12889-024-18977-x

 

  1. Lim YX, Mierzwa ML, Sartor MA, D’Silva NJ. Clinical, morphologic and molecular heterogeneity of HPV-associated oropharyngeal cancer. Oncogene. 2023;42(40):2939-2955. doi: 10.1038/s41388-023-02819-y

 

  1. Acharya SK, Shai S, Choon YF, et al. Cancer Stem Cells in Oral Squamous Cell Carcinoma: A Narrative Review on Experimental Characteristics and Methodological Challenges. Biomedicines. 2024;12(9):2111. doi: 10.3390/biomedicines12092111

 

  1. Amtha R, Gunardi I, Widyarman AS, et al. Salivary Profile Analysis Based on Oral Cancer Risk Habits: An Observational Cross-Sectional Study. Biomedicines. 2024;12(8):1748. doi: 10.3390/biomedicines12081748

 

  1. Jasim A, Li X, Octavia A, Gunardi I, Crocombe L, Sari EF. The association between betel quid use and oral potentially malignant and malignant disorders in Southeast Asian and Pacific regions: a systematic review and meta-analysis with GRADE evidence profile. Front Oral Health. 2024;5:1397179. doi: 10.3389/froh.2024.1397179

 

  1. Gravitt P, Winer R. Natural History of HPV Infection across the Lifespan: Role of Viral Latency. Viruses. 2017;9(10):267. doi: 10.3390/v9100267

 

  1. Preci DP, Almeida A, Weiler AL, Mukai Franciosi ML, Cardoso AM. Oxidative damage and antioxidants in cervical cancer. Int J Gynecol Cancer. 2021;31(2):265-271. doi: 10.1136/ijgc-2020-001587

 

  1. Quinlan JD. Human Papillomavirus: Screening, Testing, and Prevention. Am Fam Physician. 2021;104(2):152-159. PMID: 34383440. Available from: https://www.aafp.org/pubs/afp/issues/2021/0800/p152.pdf [Last accessed on].

 

  1. Mei J, Wang D, Zhang Y, et al. Portable Paper-Based Nucleic Acid Enrichment for Field Testing. Adv Sci. 2023;10(11):2205217. doi: 10.1002/advs.202205217

 

  1. Goulart LR, Colombo BFM, Lima MIS, et al. Expanded HPV Genotyping by Single-Tube Nested-Multiplex PCR May Explain HPV-Related Disease Recurrence. Microorganisms. 2024;12(11):2326. doi: 10.3390/microorganisms12112326

 

  1. Mattox AK, D’Souza G, Khan Z, et al. Comparison of next generation sequencing, droplet digital PCR, and quantitative real-time PCR for the earlier detection and quantification of HPV in HPV-positive oropharyngeal cancer. Oral Oncol. 2022;128:105805. doi: 10.1016/j.oraloncology.2022.105805

 

  1. Nuovo G. A broad-based approach to differentiate CIN from its mimics: The utility of in situ hybridization and immunohistochemistry. Ann Diagn Pathol. 2020;46:151515. doi: 10.1016/j.anndiagpath.2020.151515

 

  1. Shrestha T, Choi W, Kim GE, Yang JM, Yoon KC. Human papilloma virus identification in ocular surface squamous neoplasia by p16 immunohistochemistry and DNA chip test: A strobe-compliant article. Medicine. 2019;98(2):e13944. doi: 10.1097/MD.0000000000013944

 

  1. El-Salem F, Mansour M, Gitman M, et al. Real-time PCR HPV genotyping in fine needle aspirations of metastatic head and neck squamous cell carcinoma: Exposing the limitations of conventional p16 immunostaining. Oral Oncol. 2019;90:74-79. doi: 10.1016/j.oraloncology.2019.02.006

 

  1. Mirghani H, Casiraghi O, Guerlain J, et al. Diagnosis of HPV driven oropharyngeal cancers: Comparing p16 based algorithms with the RNAscope HPV-test. Oral Oncol. 2016;62:101-108. doi: 10.1016/j.oraloncology.2016.10.009

 

  1. Yin L, Zhao Z, Wang C, et al. Development and evaluation of a CRISPR/Cas12a-based diagnostic test for rapid detection and genotyping of HR-HPV in clinical specimens. Microbiol Spectr. 2025;13(1):e02253-24. doi: 10.1128/spectrum.02253-24

 

  1. Thai DA, Liu J, Gutierrez Ruiz A, Zhang Y, Walther-Antonio M, Liu Y. Triple-mode point-of-care diagnostics for high- risk human papillomavirus in urine. Biosens Bioelectron X. 2025;26:100658. doi: 10.1016/j.biosx.2025.100658

 

  1. Guan X, Yang R, Zhang J, et al. Programmable Multiplexed Nucleic Acid Detection by Harnessing Specificity Defect of CRISPR-Cas12a. Adv Sci. 2025;12(4):2411021. doi: 10.1002/advs.202411021

 

  1. Yin K, Pandian V, Kadimisetty K, et al. Synergistically enhanced colorimetric molecular detection using smart cup: a case for instrument-free HPV-associated cancer screening. Theranostics. 2019;9(9):2637-2645. doi: 10.7150/thno.32224

 

  1. Hartanti MD, Amtha R, Wratsangka R, et al. Operational Feasibility and Performance of mRPA Versus PCR for the Detection of HPV Types 16, 18, and 52 in Clinical Samples: An Exploratory Study. Int J Womens Health. 2025;17:955- 964. doi: 10.2147/IJWH.S496621

 

  1. Wormald B, Rodriguez-Manzano J, Moser N, et al. Loop- Mediated Isothermal Amplification Assay for Detecting Tumor Markers and Human Papillomavirus: Accuracy and Supplemental Diagnostic Value to Endovaginal MRI in Cervical Cancer. Front Oncol. 2021;11:747614. doi: 10.3389/fonc.2021.747614

 

  1. Petry KU, Schmidt D, Scherbring S, et al. Triaging Pap cytology negative, HPV positive cervical cancer screening results with p16/Ki-67 Dual-stained cytology. Gynecol Oncol. 2011;121(3):505-509. doi: 10.1016/j.ygyno.2011.02.033

 

  1. Ekanayake Weeramange C, Liu Z, Hartel G, et al. Salivary High-Risk Human Papillomavirus (HPV) DNA as a Biomarker for HPV-Driven Head and Neck Cancers. J Mol Diagn. 2021;23(10):1334-1342. doi: 10.1016/j.jmoldx.2021.07.005

 

  1. Randén-Brady R, Carpén T, Jouhi L, et al. In situ hybridization for high-risk HPV E6/E7 mRNA is a superior method for detecting transcriptionally active HPV in oropharyngeal cancer. Hum Pathol. 2019;90:97-105. doi: 10.1016/j.humpath.2019.05.006

 

  1. Li T, Wu Z, Jiang M, et al. Clinical performance of Onclarity HPV assay and Cobas HPV test in detection of cervical precancer and cancer in Chinese women. Gynecol Oncol. 2020;157(1):202-208. doi: 10.1016/j.ygyno.2020.01.011

 

  1. Zhang K, Li Q, Wang K, et al. RPA-CRISPR-Cas-mediated dual lateral flow assay for the point-of-care testing of HPV16 and HPV18. Bioconjug Chem. 2024;35(11):1797-1804. doi: 10.1021/acs.bioconjchem.4c00375

 

  1. Gomes M, Provaggi E, Pembe AB, Olaitan A, Gentry- Maharaj A. Advancing Cervical Cancer Prevention Equity: Innovations in Self-Sampling and Digital Health Technologies Across Healthcare Settings. Diagnostics. 2025;15(9):1176. doi: 10.3390/diagnostics15091176
Share
Back to top
Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept