TY - JOUR
T1 - Type-specific viral load and physical state of HPV Type 16, 18, and 58 as diagnostic biomarkers for high-grade squamous intraepithelial lesions or cervical cancer
AU - Kim, Jongseung
AU - Kim, Bu Kyung
AU - Jeon, Dongsoo
AU - Lee, Chae Hyeong
AU - Roh, Ju Won
AU - Kim, Joo Young
AU - Park, Sang Yoon
N1 - Publisher Copyright:
©2020 by the Korean Cancer Association.
PY - 2020
Y1 - 2020
N2 - Purpose High rate of false-positive tests is a major obstacle to use human papillomavirus (HPV) detection as a diagnostic tool for high-grade squamous intraepithelial lesions or cervical cancer (HSIL+). We investigated whether type-specific viral load or physical state of HPV 16, 18, and 58 are useful biomarkers for HSIL+. Materials and Methods Type-specific viral loads of E6 and E2 genes in cervical cells from 240, 83, and 79 HPV 16 , 18 , and 58 infected women, respectively, were determined using real-time polymerase chain reaction. Viral loads were normalized to cellular DNA (copy/cell). Total and integrated viral loads and physical state were compared between HSIL+ and controls, and diagnostic value was determined using receiver operating characteristic analysis. Results Viral loads of HPV 16, 18, and 58 were significantly different in lesions in the same pathologic grade. High type-specific total viral loads were significantly associated with HSIL+ (odds ratio [OR], 14.065, 39.472, and 7.103 for HPV 16, 18, and 58, respectively). High integrated viral load was related to HSIL+ in women with HPV 16 (OR, 8.242), and integrated state was associated with HSIL+ in women with HPV 18 (OR, 9.443). Type-specific total viral load was significantly associated with HSIL+ (area under curve, 0.914, 0.937, and 0.971 for HPV 16, 18, and 58, respectively), indicating an excellent performance in detecting HSIL+. Conclusion Type-specific total viral load may be a powerful diagnostic marker for HSIL+ in HPV 16 , 18 , and 58 infected HSIL+ lesions. If demonstrated in all other high-risk HPV types, this method can lead to a paradigm shift in the strategy of equivocal cytologic abnormalities.
AB - Purpose High rate of false-positive tests is a major obstacle to use human papillomavirus (HPV) detection as a diagnostic tool for high-grade squamous intraepithelial lesions or cervical cancer (HSIL+). We investigated whether type-specific viral load or physical state of HPV 16, 18, and 58 are useful biomarkers for HSIL+. Materials and Methods Type-specific viral loads of E6 and E2 genes in cervical cells from 240, 83, and 79 HPV 16 , 18 , and 58 infected women, respectively, were determined using real-time polymerase chain reaction. Viral loads were normalized to cellular DNA (copy/cell). Total and integrated viral loads and physical state were compared between HSIL+ and controls, and diagnostic value was determined using receiver operating characteristic analysis. Results Viral loads of HPV 16, 18, and 58 were significantly different in lesions in the same pathologic grade. High type-specific total viral loads were significantly associated with HSIL+ (odds ratio [OR], 14.065, 39.472, and 7.103 for HPV 16, 18, and 58, respectively). High integrated viral load was related to HSIL+ in women with HPV 16 (OR, 8.242), and integrated state was associated with HSIL+ in women with HPV 18 (OR, 9.443). Type-specific total viral load was significantly associated with HSIL+ (area under curve, 0.914, 0.937, and 0.971 for HPV 16, 18, and 58, respectively), indicating an excellent performance in detecting HSIL+. Conclusion Type-specific total viral load may be a powerful diagnostic marker for HSIL+ in HPV 16 , 18 , and 58 infected HSIL+ lesions. If demonstrated in all other high-risk HPV types, this method can lead to a paradigm shift in the strategy of equivocal cytologic abnormalities.
KW - Cervical cancer
KW - High-grade squamous intraepithelial lesions
KW - Human papillomavirus
KW - Viral load
UR - http://www.scopus.com/inward/record.url?scp=85083389591&partnerID=8YFLogxK
U2 - 10.4143/crt.2019.152
DO - 10.4143/crt.2019.152
M3 - Article
C2 - 31476849
AN - SCOPUS:85083389591
SN - 1598-2998
VL - 52
SP - 396
EP - 405
JO - Cancer Research and Treatment
JF - Cancer Research and Treatment
IS - 2
ER -