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Association of antibody to E2 protein of human papillomavirus and p16INK4A with progression of HPV-infected cervical lesions

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Abstract

Human papillomavirus (HPV) E2 and L1 proteins are expressed in cervical cells during the lytic stage of infection. Overexpression of p16INK4A is a biomarker of HPV-associated cervical neoplasia. This study investigated antibodies to HPV16 E2, HPV16 L1, and p16INK4A in sera from women with no squamous intraepithelial lesion (No-SIL) of the cervix, low-grade SIL, high-grade SIL, and cervical squamous cell carcinoma (SCC). HPV DNA was detected by polymerase chain reaction. Anti-E2, -L1, and -p16INK4A antibodies in sera were determined by western blot. Among 116 samples, 69 (60%) were HPV DNA-positive. Percentages seropositive for anti-E2, -L1, and -p16INK4A antibodies were 39.6, 22.4, and 23.3%, respectively. Anti-E2 antibody was significantly correlated with HPV DNA-positive cases. Eighty-seven women (75%) were regarded as infected with HPV, having at least one positive result from HPV DNA, L1, or E2 antibody. Antibody to p16INK4A was associated with HPV infection (odds = 5.444, 95% CI 1.203–24.629, P = 0.028) and precancerous cervical lesions (odds = 5.132, 95% CI 1.604–16.415, P = 0.006). Interestingly, the concurrent detection of anti-E2 and -p16INK4A antibodies was significantly associated with HPV infection (odds = 1.382, 95% CI 1.228–1.555, P = 0.044). These antibodies might be good candidate biomarkers for monitoring HPV-associated cervical lesion development to cancer.

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Acknowledgements

This project was supported by Grant of Khon Kaen University (Grant numbers 551603, 564103 and 573003) and Faculty of Medicine, Khon Kaen University (Grant number I54141), and has received scholarship under the Post-Doctoral Training Program from Research Affairs and Graduate School, Khon Kaen University, Thailand (Grant number 58443) and the Thailand Research Fund and Khon Kaen University through the Royal Golden Jubilee Ph.D. Program (Grant number PHD/0041/2557). We would like to acknowledge Prof. David Blair, for editing the MS via Publication Clinic KKU, Thailand.

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Correspondence to Tipaya Ekalaksananan.

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The sampling of human sera and cervical tissues was approved by the Khon Kaen University Ethics Committee for Human Research (No. HE531387) and the Khon Kaen Central Hospital Ethics Committee for Human Research (No. 20/04/2554), in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study, giving their authorization to access their clinical information, sera and tumor samples for research purpose.

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Chuerduangphui, J., Pientong, C., Swangphon, P. et al. Association of antibody to E2 protein of human papillomavirus and p16INK4A with progression of HPV-infected cervical lesions. Med Oncol 35, 93 (2018). https://doi.org/10.1007/s12032-018-1151-2

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