Lab-on-Chip assay of tumour markers and Human Papilloma Virus for cervical cancer detection at the point-of-care
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Published version
Author(s)
Wormald, Benjamin W
Moser, Nicolas
deSouza, Nandita M
Mantikas, Katerina-Theresa
Malpartida-Cardenas, Kenny
Type
Journal Article
Abstract
Cervical cancer affects over half a million people worldwide each year, the majority of whom are in resource-limited settings
where cytology screening is not available. As persistent human papilloma virus (HPV) infections are a key causative factor,
detection of HPV strains now complements cytology where screening services exist. This work demonstrates the efficacy of
a handheld Lab-on-Chip (LoC) device, with an external sample extraction process, in detecting cervical cancer from biopsy
samples. The device is based on Ion-Sensitive Field-Effect Transistor (ISFET) sensors used in combination with loop-mediated
isothermal amplification (LAMP) assays, to amplify HPV DNA and human telomerase reverse transcriptase (hTERT) mRNA.
These markers were selected because of their high levels of expression in cervical cancer cells, but low to nil expression in
normal cervical tissue. The achieved analytical sensitivity for the molecular targets resolved down to a single copy per reaction
for the mRNA markers, achieving a limit of detection of 102
for hTERT. In the tissue samples, HPV-16 DNA was present in 4/5
malignant and 2/5 benign tissues, with HPV-18 DNA being present in 1/5 malignant and 1/5 benign tissues. hTERT mRNA was
detected in all malignant and no benign tissues, with the demonstrated pilot data to indicate the potential for using the LoC in
cervical cancer screening in resource-limited settings on a large scale.
where cytology screening is not available. As persistent human papilloma virus (HPV) infections are a key causative factor,
detection of HPV strains now complements cytology where screening services exist. This work demonstrates the efficacy of
a handheld Lab-on-Chip (LoC) device, with an external sample extraction process, in detecting cervical cancer from biopsy
samples. The device is based on Ion-Sensitive Field-Effect Transistor (ISFET) sensors used in combination with loop-mediated
isothermal amplification (LAMP) assays, to amplify HPV DNA and human telomerase reverse transcriptase (hTERT) mRNA.
These markers were selected because of their high levels of expression in cervical cancer cells, but low to nil expression in
normal cervical tissue. The achieved analytical sensitivity for the molecular targets resolved down to a single copy per reaction
for the mRNA markers, achieving a limit of detection of 102
for hTERT. In the tissue samples, HPV-16 DNA was present in 4/5
malignant and 2/5 benign tissues, with HPV-18 DNA being present in 1/5 malignant and 1/5 benign tissues. hTERT mRNA was
detected in all malignant and no benign tissues, with the demonstrated pilot data to indicate the potential for using the LoC in
cervical cancer screening in resource-limited settings on a large scale.
Date Acceptance
2022-04-22
Citation
Scientific Reports, 12
ISSN
2045-2322
Publisher
Nature Publishing Group
Journal / Book Title
Scientific Reports
Volume
12
Copyright Statement
Tis article is licensed under a Creative Commons Attribution 4.0 International
License, which permits use, sharing, adaptation, distribution and reproduction in any medium or
format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the
Creative Commons licence, and indicate if changes were made. Te images or other third party material in this
article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the
material. If material is not included in the article’s Creative Commons licence and your intended use is not
permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
© Te Author(s) 2022
License, which permits use, sharing, adaptation, distribution and reproduction in any medium or
format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the
Creative Commons licence, and indicate if changes were made. Te images or other third party material in this
article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the
material. If material is not included in the article’s Creative Commons licence and your intended use is not
permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
© Te Author(s) 2022
License URL
Identifier
https://www.nature.com/articles/s41598-022-12557-y.pdf
Subjects
Alphapapillomavirus
Biomarkers, Tumor
Early Detection of Cancer
Female
Humans
Papillomaviridae
Papillomavirus Infections
Point-of-Care Systems
RNA, Messenger
Telomerase
Uterine Cervical Neoplasms
Humans
Papillomaviridae
Papillomavirus Infections
Telomerase
RNA, Messenger
Point-of-Care Systems
Uterine Cervical Neoplasms
Female
Alphapapillomavirus
Early Detection of Cancer
Biomarkers, Tumor
Publication Status
Published