Strategic Significance of Low Viral Load of Human Papillomavirus in Uterine Cervical Cytology Specimens

Infection with high-risk (HR) Human Papillomavirus (HPV) is associated with the development of precancerous lesions or invasive carcinoma of the uterine cervix. Thus, the high viral load (VL) of HR-HPV DNA currently serves as a representative quantitative marker for cervical cancer. However, the cli...

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Main Authors: Nora Jee-Young Park, Claire Su-Yeon Park, Ji Yun Jeong, Moonsik Kim, Su Hyun Yoo, Gun Oh Chong, Dae Gy Hong, Ji Young Park
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Diagnostics
Subjects:
Online Access:https://www.mdpi.com/2075-4418/12/8/1855
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author Nora Jee-Young Park
Claire Su-Yeon Park
Ji Yun Jeong
Moonsik Kim
Su Hyun Yoo
Gun Oh Chong
Dae Gy Hong
Ji Young Park
author_facet Nora Jee-Young Park
Claire Su-Yeon Park
Ji Yun Jeong
Moonsik Kim
Su Hyun Yoo
Gun Oh Chong
Dae Gy Hong
Ji Young Park
author_sort Nora Jee-Young Park
collection DOAJ
description Infection with high-risk (HR) Human Papillomavirus (HPV) is associated with the development of precancerous lesions or invasive carcinoma of the uterine cervix. Thus, the high viral load (VL) of HR-HPV DNA currently serves as a representative quantitative marker for cervical cancer. However, the clinical significance of low HPV DNA VL remains undetermined. This study aimed to evaluate the clinical association between the low HPV DNA VL and cytology/histologic diagnosis of cervical samples. We searched the electronic medical databases for the resultant analyses of HPV genotyping among patients who underwent treatment for any cervical lesion or who had undergone gynecological examinations with any positive HPV results according to the national cancer screening service between 2015 and 2016. HPV testing with genotyping and semi-quantitative VL measurement was conducted using an Anyplex<sup>TM</sup> II H28 Detection assay (H28 assay, Seegene, Seoul, Republic of Korea). The H28 assay is a multiplex semi-quantitative real-time PCR test using the tagging of oligonucleotide cleavage and extension (TOCE) technology. The VL was semi-quantified as high (3+; positive signal before 31 PCR cycles), intermediate (2+; positive between 31 and 39 PCR cycles), or low (1+; positive after 40 PCR cycles). Out of 5940 HPV VL analyses, 356 assays (5.99%) were reported as low VL (1+) of HPV DNA. Matched cytology diagnoses were mostly negative findings (n = 347, 97.5%), except for seven cases of atypical squamous cells of undetermined significance (1.9%) and two cases of atypical glandular cells (0.6%). During the follow-up periods, abnormal cytologic diagnoses were identified, including one case of high-grade squamous intraepithelial lesion (HSIL) and two low-grade squamous intraepithelial lesions (LSILs). The matched, confirmative histologic diagnosis of HSIL cytology was compatible with chronic inflammation, wherein the two LSILs had regular check-ups. None revealed clinically concerned outcomes associated with HPV-related squamous lesions. The cytology was most likely negative for malignancy when the VL of HPV DNA was low (1+). Additional strategic monitoring and management may thus be unnecessary.
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spelling doaj.art-e4f1eaae403546d19bf7506c7f0af5f22023-12-01T23:36:11ZengMDPI AGDiagnostics2075-44182022-07-01128185510.3390/diagnostics12081855Strategic Significance of Low Viral Load of Human Papillomavirus in Uterine Cervical Cytology SpecimensNora Jee-Young Park0Claire Su-Yeon Park1Ji Yun Jeong2Moonsik Kim3Su Hyun Yoo4Gun Oh Chong5Dae Gy Hong6Ji Young Park7Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 41404, KoreaFaculty of Nursing, University of Alberta, Edmonton, AB T6G 2B7, CanadaDepartment of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 41404, KoreaDepartment of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 41404, KoreaDepartment of Pathology, National Police Hospital, Seoul 05715, KoreaClinical Omics Research Center, School of Medicine, Kyungpook National University, Daegu 41405, KoreaDepartment of Obstetrics and Gynecology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 41404, KoreaDepartment of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 41404, KoreaInfection with high-risk (HR) Human Papillomavirus (HPV) is associated with the development of precancerous lesions or invasive carcinoma of the uterine cervix. Thus, the high viral load (VL) of HR-HPV DNA currently serves as a representative quantitative marker for cervical cancer. However, the clinical significance of low HPV DNA VL remains undetermined. This study aimed to evaluate the clinical association between the low HPV DNA VL and cytology/histologic diagnosis of cervical samples. We searched the electronic medical databases for the resultant analyses of HPV genotyping among patients who underwent treatment for any cervical lesion or who had undergone gynecological examinations with any positive HPV results according to the national cancer screening service between 2015 and 2016. HPV testing with genotyping and semi-quantitative VL measurement was conducted using an Anyplex<sup>TM</sup> II H28 Detection assay (H28 assay, Seegene, Seoul, Republic of Korea). The H28 assay is a multiplex semi-quantitative real-time PCR test using the tagging of oligonucleotide cleavage and extension (TOCE) technology. The VL was semi-quantified as high (3+; positive signal before 31 PCR cycles), intermediate (2+; positive between 31 and 39 PCR cycles), or low (1+; positive after 40 PCR cycles). Out of 5940 HPV VL analyses, 356 assays (5.99%) were reported as low VL (1+) of HPV DNA. Matched cytology diagnoses were mostly negative findings (n = 347, 97.5%), except for seven cases of atypical squamous cells of undetermined significance (1.9%) and two cases of atypical glandular cells (0.6%). During the follow-up periods, abnormal cytologic diagnoses were identified, including one case of high-grade squamous intraepithelial lesion (HSIL) and two low-grade squamous intraepithelial lesions (LSILs). The matched, confirmative histologic diagnosis of HSIL cytology was compatible with chronic inflammation, wherein the two LSILs had regular check-ups. None revealed clinically concerned outcomes associated with HPV-related squamous lesions. The cytology was most likely negative for malignancy when the VL of HPV DNA was low (1+). Additional strategic monitoring and management may thus be unnecessary.https://www.mdpi.com/2075-4418/12/8/1855Human PapillomavirusHPV DNAviral loadcervical cytologyshared decision making
spellingShingle Nora Jee-Young Park
Claire Su-Yeon Park
Ji Yun Jeong
Moonsik Kim
Su Hyun Yoo
Gun Oh Chong
Dae Gy Hong
Ji Young Park
Strategic Significance of Low Viral Load of Human Papillomavirus in Uterine Cervical Cytology Specimens
Diagnostics
Human Papillomavirus
HPV DNA
viral load
cervical cytology
shared decision making
title Strategic Significance of Low Viral Load of Human Papillomavirus in Uterine Cervical Cytology Specimens
title_full Strategic Significance of Low Viral Load of Human Papillomavirus in Uterine Cervical Cytology Specimens
title_fullStr Strategic Significance of Low Viral Load of Human Papillomavirus in Uterine Cervical Cytology Specimens
title_full_unstemmed Strategic Significance of Low Viral Load of Human Papillomavirus in Uterine Cervical Cytology Specimens
title_short Strategic Significance of Low Viral Load of Human Papillomavirus in Uterine Cervical Cytology Specimens
title_sort strategic significance of low viral load of human papillomavirus in uterine cervical cytology specimens
topic Human Papillomavirus
HPV DNA
viral load
cervical cytology
shared decision making
url https://www.mdpi.com/2075-4418/12/8/1855
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